Profilaxis antiepiléptica en meningiomas: revisión sistemática y metaanálisis / Seizure prophylaxis in meningiomas: A systematic review and meta-analysis

Introducción: En la actualidad, no existe una indicación formal de profilaxis anticomicial en neurocirugía oncológica. Tampoco existen recomendaciones específicas sobre el uso de fármacos antiepilépticos (FAE) en pacientes portadores de meningiomas y libres de crisis que van a ser intervenidos. En general, se prescriben FAE de forma discrecional, teniendo en cuenta diversos factores de riesgo clínico-radiológicos. Presentamos una revisión sistemática y metaanálisis sobre la efectividad de la profilaxis anticomicial en meningiomas sin historia previa de crisis. Métodos: Se realizó una búsqueda sistemática en las bases de datos PubMed/MEDLINE, Cochrane Central Register of Controlled trials, Embase y clinicaltrials.gov. De los 4.368 estudios inicialmente identificados, finalmente se incluyeron 12 para la extracción de datos y análisis cualitativo. Los datos clínicos permitieron incluir únicamente 6 estudios en el metaanálisis. Se realizaron estudios de heterogeneidad, cálculo de OR combinada, evaluación del sesgo de publicación y análisis de sensibilidad. Resultados: La profilaxis con FAE en meningiomas sin crisis previas no redujo de forma significativa la incidencia de crisis postoperatorias respecto a los controles (OR combinada de Mantle-Haenszel, efectos aleatorios, de 1,26, IC del 95%, 0,60-2,78, sobre 2.041 pacientes). Sin embargo, la ausencia de estudios prospectivos, la presencia de sesgo de selección en los estudios, una probable infraestimación del número de crisis durante el seguimiento y la influencia marcada de un estudio sobre el efecto global impiden establecer una recomendación sólida en contra de la profilaxis anticomicial. Conclusiones: Dentro de las limitaciones de esta revisión, los resultados del metaanálisis no apoyan el uso rutinario de la profilaxis antiepiléptica en pacientes con meningiomas sin historia previa de crisis.(AU)

Introduction: No formal indication currently exists for seizure prophylaxis in neurosurgical oncology patients. Neither have specific recommendations been made on the use of antiepileptic drugs (AED) in seizure-free patients with meningiomas scheduled for surgery. AEDs are generally prescribed on a discretionary basis, taking into consideration a range of clinical and radiological risk factors. We present a systematic review and meta-analysis exploring the effectiveness of antiepileptic prophylaxis in patients with meningioma and no history of seizures. Methods: We performed a systematic review of the PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Embase, and clinicaltrials.gov databases. Of a total of 4368 studies initially identified, 12 were selected for extraction of data and qualitative analysis. Based on the clinical data presented, we were only able to include 6 studies in the meta-analysis. We performed heterogeneity studies, calculated a combined odds ratio, evaluated publication bias, and conducted a sensitivity analysis. Results: AED prophylaxis in patients with meningioma and no history of seizures did not significantly reduce the incidence of post-operative seizures in comparison to controls (Mantel-Haenszel combined odds ratio, random effects model: 1.26 [95% confidence interval, 0.60-2.78]; 2041 patients). However, we are unable to establish a robust recommendation against this treatment due to the lack of prospective studies, the presence of selection bias in the studies reviewed, the likelihood of underestimation of seizure frequency during follow-up, and the strong influence of one study on the overall effect. Conclusions: Despite the limitations of this review, the results of the meta-analysis do not support the routine use of seizure prophylaxis in patients with meningioma and no history of seizures.(AU)

Seizure prophylaxis in meningiomas: a systematic review and meta-analysis.

INTRODUCTION: No formal indication currently exists for seizure prophylaxis in neurosurgical oncology patients. Neither have specific recommendations been made on the use of antiepileptic drugs (AED) in seizure-free patients with meningiomas scheduled for surgery. AEDs are generally prescribed on a discretionary basis, taking into consideration a range of clinical and radiological risk factors. We present a systematic review and meta-analysis exploring the effectiveness of antiepileptic prophylaxis in patients with meningioma and no history of seizures. METHODS: We performed a systematic review of the PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Embase, and clinicaltrials.gov databases. Of a total of 4368 studies initially identified, 12 were selected for extraction of data and qualitative analysis. Based on the clinical data presented, we were only able to include 6 studies in the meta-analysis. We performed heterogeneity studies, calculated a combined odds ratio, evaluated publication bias, and conducted a sensitivity analysis. RESULTS: AED prophylaxis in patients with meningioma and no history of seizures did not significantly reduce the incidence of post-operative seizures in comparison to controls (Mantel-Haenszel combined odds ratio, random effects model: 1.26 [95% confidence interval, 0.60-2.78]; 2041 patients). However, we are unable to establish a robust recommendation against this treatment due to the lack of prospective studies, the presence of selection bias in the studies reviewed, the likelihood of underestimation of seizure frequency during follow-up, and the strong influence of one study on the overall effect. CONCLUSIONS: Despite the limitations of this review, the results of the meta-analysis do not support the routine use of seizure prophylaxis in patients with meningioma and no history of seizures.

Role of adjuvant radiotherapy in atypical (WHO grade II) and anaplastic (WHO grade III) meningiomas: a systematic review

The systematic adoption of the histopathologic criteria provided by the 2016 update of the WHO classification of brain tumors has markedly increased the relative proportion of atypical and anaplastic meningiomas. These tumors exhibit a much greater recurrence rate compared to benign meningiomas, which negatively impacts survival. In recent years, the publication of numerous retrospective case series, yet no randomized controlled trials, on the impact of radiation therapy in non-benign meningioma, has yielded conflicting evidence. At present, maximum safe resection, including the dural attachment, is the preferred primary treatment modality for all types of meningiomas. Adjuvant radiotherapy is currently recommended for subtotally resected grade II and for all grade III meningiomas. However, in grade II meningiomas achieving complete resection, close radiologic and clinical observation is a feasible option. Despite the great amount of non-benign meningiomas available and eligible for trials, there is a striking lack of prospective studies testing adjuvant therapies against observation for this subset of patients. An updated and systematic literature review is provided on the effectiveness and indications of radiotherapy on grade II and III meningiomas (AU)

Role of adjuvant radiotherapy in atypical (WHO grade II) and anaplastic (WHO grade III) meningiomas: a systematic review.

The systematic adoption of the histopathologic criteria provided by the 2016 update of the WHO classification of brain tumors has markedly increased the relative proportion of atypical and anaplastic meningiomas. These tumors exhibit a much greater recurrence rate compared to benign meningiomas, which negatively impacts survival. In recent years, the publication of numerous retrospective case series, yet no randomized controlled trials, on the impact of radiation therapy in non-benign meningioma, has yielded conflicting evidence. At present, maximum safe resection, including the dural attachment, is the preferred primary treatment modality for all types of meningiomas. Adjuvant radiotherapy is currently recommended for subtotally resected grade II and for all grade III meningiomas. However, in grade II meningiomas achieving complete resection, close radiologic and clinical observation is a feasible option. Despite the great amount of non-benign meningiomas available and eligible for trials, there is a striking lack of prospective studies testing adjuvant therapies against observation for this subset of patients. An updated and systematic literature review is provided on the effectiveness and indications of radiotherapy on grade II and III meningiomas.

Seizure prophylaxis in meningiomas: A systematic review and meta-analysis. / Profilaxis antiepiléptica en meningiomas: revisión sistemática y metaanálisis.

INTRODUCTION: No formal indication currently exists for seizure prophylaxis in neurosurgical oncology patients. Neither have specific recommendations been made on the use of antiepileptic drugs (AED) in seizure-free patients with meningiomas scheduled for surgery. AEDs are generally prescribed on a discretionary basis, taking into consideration a range of clinical and radiological risk factors. We present a systematic review and meta-analysis exploring the effectiveness of antiepileptic prophylaxis in patients with meningioma and no history of seizures. METHODS: We performed a systematic review of the PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Embase, and clinicaltrials.gov databases. Of a total of 4368 studies initially identified, 12 were selected for extraction of data and qualitative analysis. Based on the clinical data presented, we were only able to include 6 studies in the meta-analysis. We performed heterogeneity studies, calculated a combined odds ratio, evaluated publication bias, and conducted a sensitivity analysis. RESULTS: AED prophylaxis in patients with meningioma and no history of seizures did not significantly reduce the incidence of post-operative seizures in comparison to controls (Mantel-Haenszel combined odds ratio, random effects model: 1.26 [95% confidence interval, 0.60-2.78]; 2041 patients). However, we are unable to establish a robust recommendation against this treatment due to the lack of prospective studies, the presence of selection bias in the studies reviewed, the likelihood of underestimation of seizure frequency during follow-up, and the strong influence of one study on the overall effect. CONCLUSIONS: Despite the limitations of this review, the results of the meta-analysis do not support the routine use of seizure prophylaxis in patients with meningioma and no history of seizures.

A comprehensive overview on the molecular biology of human glioma: what the clinician needs to know.

The molecular biology of human glioma is a complex and fast-growing field in which basic research needs to meet clinical expectations in terms of anti-tumor efficacy. Although much effort is being done in molecular biology research, significant contribution to the quality of life and overall survival still lacks. The vastness of molecular biology literature makes it virtually impossible for clinicians to keep up to date in the field. This paper reviews some practical concepts regarding glioma tumorigenesis from the clinician's perspective. Five main aspects are discussed: major intracellular signaling pathways involved in glioma formation; genomic, epigenetic and transcriptomic relevant features of glioma; the prognostic and predictive values of molecular markers according to the new WHO classification of glial tumors; the importance of molecular and cellular heterogeneity in glioblastoma, responsible for its therapy resistance; and the interaction between glioma and the immune system, in view of the novel and promising targeted therapies.

Central nervous system ependymoma: clinical implications of the new molecular classification, treatment guidelines and controversial issues.

Ependymoma is an uncommon neuroepithelial tumor that may arise anywhere within the neuroaxis, both in children and in adults. It has been classically graded upon histopathological features, yet with limited clinical utility. Recently, DNA methylation profiling has provided a novel classification of ependymoma in nine molecular subgroups. This stratification method harbors prognostic value with supratentorial RELA-fusion and posterior fossa group A tumors showing a significantly shorter survival compared to the rest. Currently, the treatment of choice involves maximal safe resection and, in cases of residual disease, adjuvant conformal radiotherapy. Second-look surgery is also a feasible and recommended option for incompletely resected tumors. The role of chemotherapy is not yet established and can be considered in infants and children with relapsing disease or prior to re-intervention. Although targeted agents do not seem to play a role as adjuvant therapy, they are currently being tested for recurrent disease.

Recurrent non-functioning pituitary adenomas: a review on the new pathological classification, management guidelines and treatment options.

At least 50% of surgically resected non-functioning pituitary adenomas (NFPA) recur. Either early or late adjuvant radiotherapy is highly efficacious in controlling recurrent NFPA but associates potentially burdensome complications like hypopituitarism, vascular complications or secondary neoplasm. Reoperation is indicated in bulky tumor rests compressing the optic pathway. To date, no standardized medical therapy is available for recurrent NFPA although cabergoline and temozolomide show promising results. Guidelines on the management of recurrent NFPAs are now available. The new 2017 WHO pituitary tumor classification, based on immunohistochemistry and transcription factor assessment, identifies a group of aggressive NFPA variants that may benefit from earlier adjuvant therapy. Nevertheless, NFPA patients exhibit a reduced overall life expectancy largely due to hypopituitarism and treatment-related morbidity. The management of recurrent NFPA benefits from a multidisciplinary teamwork of surgeons, endocrinologists, radiation oncologists, ophthalmologists, pathologists and neuro-radiologists in order to provide individualized therapy and anticipate deterioration.

Treatment-related changes in glioblastoma: a review on the controversies in response assessment criteria and the concepts of true progression, pseudoprogression, pseudoresponse and radionecrosis.

The assessment of response to therapy in glioblastoma remains a challenge, because the surrogate measures of survival are subject to radiographic misinterpretation. A solid and reliable definition of progression is needed for both clinical decision-making and for evaluating response within the clinical trials. Historically, assessment criteria have used radiologic and clinical features aimed to correctly classify patients into progressive or non-progressive disease. The widely used RANO criteria are a valuable tool in disease evaluation, both in the clinical setting and in the clinical trials. However, assessment criteria have certain limitations that emerging image techniques have tried to overcome. Differentiating true progression from treatment-related changes (like pseudoprogression or pseudoresponse) is crucial in order not to prematurely discontinue adjuvant chemotherapy or redirect the patient to second-line options. This fact underscores the need for advanced radiologic techniques, like specific diffusion and perfusion MRI sequences, MR spectroscopy and PET, which seem to play a role in distinguishing these phenomena.

Diffuse low-grade glioma: a review on the new molecular classification, natural history and current management strategies.

The management of diffuse supratentorial WHO grade II glioma remains a challenge because of the infiltrative nature of the tumor, which precludes curative therapy after total or even supratotal resection. When possible, functional-guided resection is the preferred initial treatment. Total and subtotal resections correlate with increased overall survival. High-risk patients (age >40, partial resection), especially IDH-mutated and 1p19q-codeleted oligodendroglial lesions, benefit from surgery plus adjuvant chemoradiation. Under the new 2016 WHO brain tumor classification, which now incorporates molecular parameters, all diffusely infiltrating gliomas are grouped together since they share specific genetic mutations and prognostic factors. Although low-grade gliomas cannot be regarded as benign tumors, large observational studies have shown that median survival can actually be doubled if an early, aggressive, multi-stage and personalized therapy is applied, as compared to prior wait-and-see policy series. Patients need an honest long-term therapeutic strategy that should ideally anticipate neurological, cognitive and histopathologic worsening.

Survival in glioblastoma: a review on the impact of treatment modalities.

Glioblastoma (GBM) is the most common and lethal tumor of the central nervous system. The natural history of treated GBM remains very poor with 5-year survival rates of 5 %. Survival has not significantly improved over the last decades. Currently, the best that can be offered is a modest 14-month overall median survival in patients undergoing maximum safe resection plus adjuvant chemoradiotherapy. Prognostic factors involved in survival include age, performance status, grade, specific markers (MGMT methylation, mutation of IDH1, IDH2 or TERT, 1p19q codeletion, overexpression of EGFR, etc.) and, likely, the extent of resection. Certain adjuncts to surgery, especially cortical mapping and 5-ALA fluorescence, favor higher rates of gross total resection with apparent positive impact on survival. Recurrent tumors can be offered re-intervention, participation in clinical trials, anti-angiogenic agent or local electric field therapy, without an evident impact on survival. Molecular-targeted therapies, immunotherapy and gene therapy are promising tools currently under research.

Dexamethasone treatment in chronic subdural haematoma.

INTRODUCTION: Neurosurgeons are familiar with chronic subdural haematoma (CSH), a well-known clinical entity, which is usually treated by some modality of trepanation. Despite the excellent outcomes obtained by surgery, complications may occur, some of which may be potentially severe or fatal. Furthermore, up to 25% recurrence rate is reported. The authors present a novel approach to the management of CSH based on the use of dexamethasone as the treatment of choice in the majority of cases. PATIENTS AND METHODS: Medical records of 122 CSH patients were retrospectively reviewed. At admission, symptomatic patients were classified according to the Markwalder Grading Score (MGS). Those scoring MGS 1-2 were assigned to the Dexamethasone protocol (4 mg every 8h, re-evaluation after 48-72 h, slow tapering), and those scoring MGS 3-4 were, in general, assigned to the Surgical protocol (single frontal twistdrill drainage to a closed system, without irrigation). Patients were followed in the Outpatient Office with neurological assessment and serial CT scans. RESULTS. Between March 2001 and May 2006, 122 consecutive CSH patients (69% male, median aged of 78, range 25-97) were treated. Seventy-three percent of the patients exhibited some kind of neurological defect (MGS 2-3-4). Asymptomatic patients (MGS 0) were left untreated. Initial treatment assignment was: 101 dexamethasone, 15 subdural drain, 4 craneotomy and 2 untreated. Twenty-two patients on dexamethasone ultimately required surgical drain (21.8%). Favourable outcome (MGS 0-1-2) was obtained in 96% and 93.9% of those treated with dexamethasone and surgical drain, respectively. Median hospital stay was 6 days (range 1- 41) for the dexamethasone group and the whole series, and 8 days (range 5-48) for the surgical group. Overall mortality rate was 0.8% and re-admissions related to the haematoma reached 14.7% (all maintained or improved their MGS). Medical complications occurred in 34 patients (27.8%), mainly mild hyperglycemic impairments. Median outpatient follow up was 25 weeks (range 8-90), and two patients were lost. DISCUSSION: The rationale for the use of dexamethasone in CSH lies in its anti-angiogenic properties over the subdural clot membrane, as it is derived from experimental studies and the very few clinical observations published. Surgical evacuation of CSH is known to achieve excellent results but no well-designed trials compare medical versus surgical therapies. The experience obtained from this series lets us formulate some clinical considerations: dexamethasone is a feasible treatment that positively compares to surgical drain (and avoided two thirds of operations); the natural history of CSH allows a 48-72 h dexamethasone trial without putting the patient at risk of irreversible deterioration; eliminates all morbidity related to surgery and recurrences; does not provoke significant morbidity itself; reduces hospital stay; does not preclude ulterior surgical procedures; it is well tolerated and understood by the patient and relatives and it probably reduces costs. The authors propose a protocol that does not intend to substitute surgery but to offer a safe and effective alternative. CONCLUSION: Data obtained from this large retrospective series suggests that dexamethasone is a feasible and safe option in the management of CSH. In the author's experience dexamethasone was able to cure or improve two thirds of the patients. This fact should be confirmed by others in the future. The true effectiveness of the therapy as compared to surgical treatment could be ideally tested in a prospective randomized trial.

Large chondroma of the dural convexity in a patient with Noonan's syndrome. Case report and review of the literature.

INTRODUCTION: Intracranial chondromas are extremely rare intracranial tumours that usually arise from the skull base synchondrosis. Exceptionally, they may grow from cartilage rests within the dura mater of the convexity or the falx. They may be part of Ollier's multiple enchondromatosis or Maffuci's syndrome. We describe the case of a young male diagnosed of Noonan's syndrome that underwent resection of a large intracranial chondroma arising from the dural convexity. To our best knowledge this is the first report of such association. CASE REPORT: An 18-year-old male presented with a single generalized seizure. The patient was previously diagnosed of Noonan's syndrome on the basis of his special phenotype (Turner-like), low stature, cardiac malformation, retarded sexual and bone development and normal karyotype. He harboured mild psychomotor retardation. Physical and neurological examinations were unremarkable. Brain Magnetic Resonance image showed a large well-circumscribed intracranial mass in the dural convexity of the left frontal-parietal lobes, with heterogeneous contrast enhancement and no peritumoural oedema. The patient was initiated on valproic acid and underwent craniotomy and complete excision of the tumour. The tumour was firm, white-greyish, avascular and could be finely dissected away from the cortex. Postoperative seizures required additional anticonvulsant therapy. He was discharged uneventfully. The pathological study revealed a mature chondroma. Subsequent brain MRI studies have shown no evidence of recurrence after 33 months of follow up. DISCUSSION: Chondromas comprise less than 0.3% of intracranial tumours. Only twenty-five cases of intracranial dural convexity chondromas are reported in the literature. Several hystopathogenetic theories have been proposed: metaplasia of meningeal fibroblasts and perivascular meningeal tissue, traumatic or inflammatory cartilaginous activation of fibroblasts and growth of aberrant embryonal cartilaginous rests in the dura mater. Chondromas present clinical features similar to meningiomas. CT scan imaging shows a mass of variable density due to different degrees of calcification with minimum to moderate contrast enhancement. MRI studies show a well-circumscribed lesion without surrounding tissue oedema, that exhibit heterogeneous signal with intermediate to low intensity on T1-weighted images and mixed intensity on T2-weighted images with minimum enhancement. Angiogram is clue to differentiate from meningiomas since chondromas are completely avascular. Complete tumour resection including its dural attachment is the treatment of choice. Long-term prognosis is favourable. Radiation therapy is currently not recommended for residual tumours or inoperable patients due to risk of malignization. Noonan's syndrome (also known as pseudo-Turner syndrome) is a complex familial genetic disorder with a phenotype that resembles that of Turner's syndrome but exhibits no chromosomal defect. No predisposition of Noonan's syndrome for tumoural development is reported in the literature. Association of a dural convexity chondroma with Noonan's syndrome is unique as far as the literature is concerned.

Large chondroma of the dural convexity in a patient with Noonan’s syndrome. Case report and review of the literature

Introducción. Los condromas intracraneales sontumores extremadamente raros que suelen surgir dela sincondrosis de la base craneal. Excepcionalmente,puede crecer a partir de restos cartilaginosos en laduramadre de la convexidad o en la hoz. Se han relacionado con la encondromatosis múltiple de Ollier y con el síndrome de Maffuci. Describimos el caso de unvarón joven diagnosticado de síndrome de Noonan enel que se resecó un condroma gigante de la convexidad.Esta asociación no está descrita en la literatura hasta el momento. Caso clínico. Varón de 18 años de edad que presenta una única crisis comicial generalizada comodebut clínico. Estaba previamente diagnosticado desíndrome de Noonan basándose en su fenotipo especial(Turner-like), baja estatura, presencia de malformacióncardíaca, retraso en la maduración ósea y sexual, ycariotipo normal. No presentaba alteraciones significativas en la exploración física y neurológica salvo un leve retraso mental. El estudio de resonancia magnética cerebral mostró una masa intracraneal de gran tamaño, bien circunscrita, dependiente de la convexidad dural frontoparietal izquierda, con captación heterogéneade contraste y sin edema perilesional. Comenzó tratamiento con ácido valproico y se realizó una resección completa de la lesión. El tumor era de consistencia dura, blanco-grisáceo, avascular y pudo disecarse por completo de la corteza. Presentó crisis comiciales postoperatorias que precisaron tratamiento combinado con un segundo anticomicial. Anatomía patológica: condroma maduro. Las RM de control han mostrado ausencia de recidiva tras 33 meses de seguimiento. Discusión. Los condromas comprenden menos del 0,3% de los tumores intracraneales. Hasta la fecha, sólo se han descrito veinticinco casos de condromas de convexidad dural en la literatura. Se han propuesto diversas teorías histopatogénicas: metaplasia de fibroblastos meníngeos y tejido meníngeo perivascular, activación traumática o inflamatoria de fibroblastos hacia cartílago, y crecimiento de restos cartilaginosos embrionarios aberrantes en la duramadre. Los condromas presentan características clínicas similares a los meningiomas. La imagen de TAC muestra una masa de densidad variable debido a los diferentes grados de calcificación con mínima a moderada captación de contraste. Los estudios de RM evidencian una masa bien circunscrita sin edema perilesional, de señal heterogénea, hipointensa en T1 y de intensidad mixta en T2, y con captación mínima de contraste. La angiografía los diferencia perfectamente de los meningiomas pues aquéllos son totalmente avasculares. El tratamiento de elección es la resección completa incluyendo la duramadre adyacente. El pronóstico a largo plazo es excelente. El tratamiento con radioterapia no se recomienda ni en los restos tumorales ni en los pacientes inoperables, debido al riesgo de malignización. El síndrome de Noonan (tambiénconocido como pseudo-Turner) es una enfermedadgenética familiar compleja cuyo fenotipo se asemejaal del síndrome de Turner pero no presenta defectocromosómico. Hasta la fecha, no se ha descrito en laliteratura una predisposición al desarrollo de tumoresen los pacientes con Noonan ni tampoco la asociaciónde este síndrome con un condroma de convexidad cerebral

Introduction. Intracranial chondromas are extremelyrare intracranial tumours that usually arise fromthe skull base synchondrosis. Exceptionally, they maygrow from cartilage rests within the dura mater of theconvexity or the falx. They may be part of Ollier's multiple enchondromatosis or Maffuci's syndrome. We describe the case of a young male diagnosed of Noonan'ssyndrome that underwent resection of a large intracranialchondroma arising from the dural convexity. To our best knowledge this is the first report of such association.Case report. An 18-year-old male presented with asingle generalized seizure. The patient was previouslydiagnosed of Noonan's syndrome on the basis of hisspecial phenotype (Turner-like), low stature, cardiacmalformation, retarded sexual and bone developmentand normal karyotype. He harboured mild psychomotorretardation. Physical and neurological examinationswere unremarkable. Brain Magnetic Resonance imageshowed a large well-circumscribed intracranial massin the dural convexity of the left frontal-parietal lobes, with heterogeneous contrast enhancement and no peritumoural oedema. The patient was initiated on valproic acid and underwent craniotomy and complete excision of the tumour. The tumour was firm, white-greyish, avascular and could be finely dissected away from the cortex. Postoperative seizures required additional anticonvulsant therapy. He was discharged uneventfully. The pathological study revealed a mature chondroma. Subsequent brain MRI studies have shown no evidence of recurrence after 33 months of follow up.Discussión. Chondromas comprise less than 0.3% ofintracranial tumours. Only twenty-five cases of intracranial dural convexity chondromas are reported inthe literature. Several hystopathogenetic theories havebeen proposed: metaplasia of meningeal fibroblasts andperivascular meningeal tissue, traumatic or inflammatorycartilaginous activation of fibroblasts and growthof aberrant embryonal cartilaginous rests in the duramater. Chondromas present clinical features similar tomeningiomas. CT scan imaging shows a mass of variabledensity due to different degrees of calcification withminimum to moderate contrast enhancement. MRI studiesshow a well-circumscribed lesion without surroundingtissue oedema, that exhibit heterogeneous signalwith intermediate to low intensity on T1-weightedimages and mixed intensity on T2-weighted images withminimum enhancement. Angiogram is clue to differentiatefrom meningiomas since chondromas are completelyavascular. Complete tumour resection including itsdural attachment is the treatment of choice. Long-termprognosis is favourable. Radiation therapy is currentlynot recommended for residual tumours or inoperablepatients due to risk of malignization. Noonan's syndrome(also known as pseudo-Turner syndrome) is a complex familial genetic disorder with a phenotype that resembles that of Turner's syndrome but exhibitsno chromosomal defect. No predisposition of Noonan'ssyndrome for tumoural development is reported in theliterature. Association of a dural convexity chondromawith Noonan's syndrome is unique as far as the literatureis concerned

[Symptomatic cervical stenosis due to calcification of the ligamentum flavum after mild cervical trauma]. / Estenosis cervical sintomática por calcificación del ligamento amarillo tras traumatismo cervical leve.

INTRODUCTION: The calcification of ligamentum flavum (CLF) is a rare disease mainly affecting middle or advanced aged Japanese women. Several clinical and radiological features differentiate CLF from the ossification of the ligamentum flavum (OLF). We present a case of symptomatic cervical-dorsal stenosis presenting after mild cervical trauma in a patient with a remarkable CLF who underwent decompressive laminectomy. The literature regarding CLF is reviewed. CASE REPORT: A 65 year-old female suffered mild cervical trauma as a consequence of a car accident. A year later she referred progressive cervical and upper dorsal pain without any sensory or motor defect. Spinal magnetic resonance images showed a well-delineated posterior epidural mass, from C2 to T2, which compressed the spinal cord, without signal of myelopathy. She underwent bilateral laminectomy of the affected levels but no clear improvement occurred. The pathological study of the resected pieces showed a remarkable calcification of the ligamentum flavum. DISCUSSION: The CLF is a kind of dystrophic calcification of unknown pathogenesis but likely related to the spinal degenerative changes. It usually presents in Japanese females. A definite relation between CLF and cervical trauma has not been established so far, although the latter may possibly trigger the symptoms. Typically, CLF presents in women in the seventh decade, affects preferably the cervical region, it shows nodular or diffuse pattern in the computerized tomography, it is hypointense in TI and T2-weighted MR sequences and exhibits minimum enhancement after gadolinium administration. CLF differentiates from OLF easily by demonstrating the presence of mature bone formation in the latter. Clinically, CLF may present as radiculopathy or myelopathy. The treatment of choice in symptomatic patients is posterior decompression. Excellent results after laminectomy are reported. Future similar observations will be important from a medical-legal point of view if a relation between CLF and cervical trauma is established since CLF may potentially turn into a severe condition.

Estenosis cervical sintomática por calcificación del ligamento amarillo tras traumatismo cervical leve / Symptomatic cervical stenosis due to calcification of the ligamentum flavum after mild cervical trauma

Introducción. La calcificación del ligamento amarillo(CLA) es una rara enfermedad que afecta principalmentea mujeres de edad media o avanzada yde etnia japonesa. Diversas características clínicas yradiológicas la diferencian de la osificación del ligamentoamarillo (OLA). Presentamos un caso de estenosiscervical sintomática, aparentemente desencadenadopor un traumatismo cervical de carácter leve, en unapaciente con una extensa calcificación del ligamentoamarillo a nivel cervicodorsal que fue tratada mediantelaminectomía descompresiva. Se revisa la literatura alrespecto.Caso clínico. Mujer de 65 años que sufre traumatismocervical leve como consecuencia de atropello porautomóvil. Al año acude al servicio de Neurocirugíarefiriendo desde entonces cervicalgia y dolor interescapularque progresivamente habían aumentado enintensidad, sin afectación motora ni sensitiva. En laRMN de columna cervical se objetivó una formaciónfusiforme epidural posterior de contorno bien delimitadodesde C2 a D2, que producía compresión de lamédula cervical sin imagen de mielopatía. Se intervinomediante laminectomía descompresiva de los nivelesafectados, sin gran mejoría de los síntomas. El estudioanatomopatológico mostró una calcificación extensa delligamento amarillo.Discusión. La CLA es un tipo de calcificacióndistrófica que tiene una etiopatogenia desconocida peroposiblemente relacionada con cambios degenerativosespinales, siendo más frecuente en mujeres y en poblaciónjaponesa. No se ha descrito una relación causaldefinitiva entre traumatismo cervical y CLA, aunquees posible que aquél actúe como desencadenante de lossíntomas. El paciente tipo con CLA seria una mujeren la séptima década de la vida, que presenta una calcificaciónpreferentemente cervical, de tipo nodularo difuso en la TAC, hipointenso en las secuencias deresonancia potenciadas en T1 y T2, con mínima captaciónde gadolinio periférico y con un patrón histológicogranular. Histológicamente se diferencia de la OLApor la existencia de hueso maduro únicamente en ésta.Clínicamente puede manifestarse como mielorradiculopatía.El tratamiento quirúrgico de elección en los casossintomáticos es la laminectomía descompresiva, técnicaque, según diversos autores, obtiene excelentes resultados.De confirmarse una relación patogénica entreCLA y traumatismo cervical en futuras observaciones,sería de gran importancia medico-legal pues implicaríael desarrollo de una enfermedad potencialmente gravetras un tipo de traumatismo en principio consideradobanal

Introduction. The calcification of ligamentum flavum(CLF) is a rare disease mainly affecting middle oradvanced aged Japanese women. Several clinical andradiological features differentiate CLF from the ossificationof the ligamentum flavum (OLF). We present acase of symptomatic cervical-dorsal stenosis presentingafter mild cervical trauma in a patient with a remarkableCLF who underwent decompressive laminectomy.The literature regarding CLF is reviewed.Case report. A 65 year-old female suffered mildcervical trauma as a consequence of a car accident. Ayear later she referred progressive cervical and upperdorsal pain without any sensory or motor defect. Spinal magnetic resonance images showed a well-delineatedposterior epidural mass, from C2 to T2, which compressedthe spinal cord, without signal of myelopathy.She underwent bilateral laminectomy of the affectedlevels but no clear improvement occurred. The pathologicalstudy of the resected pieces showed a remarkablecalcification of the ligamentum flavum.Discussion. The CLF is a kind of dystrophic calcificationof unknown pathogenesis but likely related tothe spinal degenerative changes. It usually presentsin Japanese females. A definite relation between CLFand cervical trauma has not been established so far,although the latter may possibly trigger the symptoms.Typically, CLF presents in women in the seventh decade,affects preferably the cervical region, it shows nodularor diffuse pattern in the computerized tomography, itis hypointense in TI and T2-weighted MR sequencesand exhibits minimum enhancement after gadoliniumadministration. CLF differentiates from OLF easily bydemonstrating the presence of mature bone formationin the latter. Clinically, CLF may present as radiculopathyor myelopathy. The treatment of choice in symptomaticpatients is posterior decompression. Excellentresults after laminectomy are reported. Future similarobservations will be important from a medical-legalpoint of view if a relation between CLF and cervicaltrauma is established since CLF may potentially turninto a severe condition

Metastatic meningioma to the eleventh dorsal vertebral body: total en bloc spondylectomy. Case report and review of the literature.

INTRODUCTION: One in every thousand intracranial meningiomas metastatize extracranially. Lung and intraabdominal organs are most frequently affected. Only 7% involve vertebrae and just a dozen cases have been reported in the literature. To our knowledge, this is the first description of a total en bloc spondylectomy through a posterior approach for the treatment of an intraosseous metastatic meningioma to the eleventh dorsal vertebra. CASE REPORT: In March 1996, a 37 year-old male underwent surgical resection for a left occipital intraventricular benign meningioma (WHO I). He was reoperated in February 2002 due to local recurrence. By the end on 2003 he developed progressively invalidating dorsolumbar pain. MRI studies revealed a T11 intraosseous mass. In March 2004, a percutaneous biopsy and vertebroplasty were performed. The pathological specimen was identified as adenocarcinoma and he initiated chemotherapy. Advice from a second pathologist was seeked, who suggested the diagnosis of intraosseous meningioma. Workup studies failed to reveal any primary tumor. In May 2004 the patient was admitted to our department and a new transpedicular biopsy confirmed the diagnosis. In June 2004 he underwent T11 total en bloc spondylectomy (Tomita's procedure), fusion with bone and calcium substitute-filled stackable carbon-fiber cages, and T9 to L1 transpedicular screw fixation. No postoperative complications ocurred and he is, so far, free from primary and secondary disease. Definite pathology: benign meningioma (WHO I). DISCUSSION: Distant metastases from intracranial meningiomas are rare entities, arising from benign lesions in, at least, 60% of cases. Enam et al proposed a specific pathological score to differentiate benign, atypic and malignant meningiomas. Such score correlates with the chance of metastatizing: more than 40% in malignant meningiomas compared to 3.8% of brain tumors overall. The ability to metastatize seems to be linked to vascular or lifatic invasiveness. Metastases ocurr more frequently in angioblastic, papillary and meningothelial variants. Hematogenous (especially venous; Batson's perivertebral plexus), linfatic and cerebrospinal fluid are the main routes involved in the spreading of the tumor. Craniotomy itself may also play a role, for the majority of patients have been previously operated on repeatedly. The interval between the onset of the intracranial disease and the appearance of the metastasis varies from months to many years. The value of transpedicular biopsy is widely recognized (efficacy over 80%) and the suitability of the specimen for pathological examination improves when wide inner caliber trephines are used. In the case presented we applied the oncologic concept of vertebral en bloc resection. We believe this case represents a paradigmatic indication of this technique because it respects the concepts of radical resection and spinal stability, and offers an opportunity for the curation of the disease.

Metastatic meningioma to the eleventh dorsal vertebral body: total en bloc spondylectomy. Case report and review of the literature

Introducción. Las metástasis distantes de meningioma intracraneal ocurren en uno de cada milmeningiomas. La mayor parte afectan a pulmón u órganos intraabdominales. Sólo un 7% aparecen en vértebras. Se han publicado en torno a una docena de casos. Presentamos la primera descripción hasta la fecha de una vertebrectomía completa por vía posterior para tratar una metástasis intraósea de meningioma benigno en el cuerpo de T11.Caso clínico. Varón de 37 años de edad, intervenido en otro centro en Marzo de 1996 de meningioma benigno intraventricular occipital izquierdo de tipo transicional(OMS tipo I). Precisó reintervención por recidiva local en Febrero de 2002. A finales de 2003 comenzó con dolor dorso lumbar intenso y el estudio de RM espinal evidenció una masa intrósea en T11. En Marzo de 2004se realizó biopsia transpedicular y vertebroplastia acrílica. El resultado histológico fue de adenocarcinoma y el paciente comenzó a recibir quimioterapia. Una segunda opinión sobre las muestras histológicas sugirió el diagnóstico de meningioma. El estudio de extensión tumoral no evidenció otra neoplasia primaria. En Mayo de 2004 ingresó en nuestro servicio donde se repite la biopsia transpedicular que confirma el diagnóstico de meningioma. En Junio de 2004 se realizó vertebrectomíaT11 completa por vía posterior, según técnica de Tomita, artrodesis intersomática con cajas apilables de fibra de carbono rellenas de injerto óseo y sustituto cálcico, y fijación transpedicular T9 a L1. La evolución postoperatoria fue satisfactoria y, actualmente, se encuentra libre de enfermedad primaria y secundaria. Anatomía patológica definitiva: meningioma benigno(OMS I).Discusión. Las metástasis distantes de meningiomas intracraneales son entidades raras que en más del 60%de los casos provienen de meningiomas benignos. Enamy cols diseñaron una gradación según parámetros histológicos para diferenciar los meningiomas benignos e los atípicos y malignos. Dicha gradación correlaciona con la probabilidad de producir metástasis distantes: más del 40% en los meningiomas malignos frente a una media del 3.8% de todos los tumores cerebrales. La posibilidad de metastatizar parece relacionarse con la capacidad de invasividad vascular o linfática. Las metástasis son más frecuentes en las variantes angioblástica, papilar y meningotelial. Se describen tres vías de diseminación: hematógena (sobre todo venosa; plexo perivertebral de Batson) linfática y por LCR. La craneotomía podría ser otra vía de diseminación pues la mayoría de los pacientes han sido previamente multioperados del tumor craneal. El tiempo transcurrido entre el diagnóstico del meningioma intracraneal y la aparición de la metástasis vertebral puede variar entremeses y años. La rentabilidad diagnóstica de la biopsia transpedicular es mayor del 80% y mejora cuanto mayor es el diámetro interno de la trefina utilizada. En el caso descrito, aplicamos el concepto oncológico de resección en bloque de la vértebra afectada. Creemos que se trata de una indicación paradigmática de esta técnica pues respeta los conceptos de resección radical y estabilidad de la columna, y otorga una oportunidad de curación de la enfermedad

Introduction. One in every thousand intracranial meningiomas metastatize extracranially. Lung andintra abdominal organs are most frequently affected. Only 7% involve vertebrae and just a dozen cases have been reported in the literature. To our knowledge, this is the first description of a total en bloc spondylectomy through a posterior approach for the treatment of an intraosseous metastatic meningioma to the eleventh dorsal vertebra. Case report. In March 1996, a 37 year-old male underwent surgical resection for a left occipital intraventricular benign meningioma (WHO I). He wasreoperated in February 2002 due to local recurrence. By the end on 2003 he developed progressively invalidating dorso lumbar pain. MRI studies revealed a T11 intraosseous mass. In March 2004, a percutaneous biopsy and vertebroplasty were performed. The pathological specimen was identified as adenocarcinoma and he initiated chemotherapy. Advice from a second pathologist was seeked, who suggested the diagnosis of intraosseous meningioma. Workup studies failed to reveal any primary tumor. In May 2004 the patient was admitted to our department and a new transpedicular biopsy confirmed the diagnosis. In June 2004 he underwentT11 total en bloc spondylectomy (Tomita's procedure),fusion with bone and calcium substitute-filled stackable carbon-fiber cages, and T9 to L1 transpedicular screw fixation. No postoperative complications ocurred and he is, so far, free from primary and secondary disease. Definite pathology: benign meningioma (WHO I).Discussion. Distant metastases from intracranial meningioma’s are rare entities, arising from benign lesions in, at least, 60% of cases. En am et al proposed a specific pathological score to differentiate benign, atypic and malignant meningiomas. Such score correlates with the chance of metastatizing: more than 40%in malignant meningiomas compared to 3.8% of brain tumors overall. The ability to metastatize seems to be linked to vascular or lifatic invasiveness. Metastases ocurr more frequently in angioblastic, papillary and meningothelial variants. Hematogenous (especially venous; Batson's perivertebral plexus), linfatic and cerebrospinal fluid are the main routes involved in the spreading of the tumor. Craniotomy itself may also play a role, for the majority of patients have been previously operated on repeatedly. The interval between the onset of the intracranial disease and the appearance of the metastasis varies from months to many years. The value of transpedicular biopsy is widely recognized (efficacy over 80%) and the suitability of the specimen for pathological examination improves when wide inner caliber trephines are used. In the case presented we applied the oncologic concept of vertebral en bloc resection. We believe this case represents a paradigmatic indication of this technique because it respects the concepts of radical resection and spinal stability, and offers an opportunity for the curation of the disease

Papel de la cirugía en la enfermedad degenerativa espinal. Análisis de revisiones sistemáticas sobre tratamientos quirúrgicos y conservadores desde el punto de vista de la medicina basada en la evidencia / Role of surgery in spinal degenerative disease. Analysis of systematic reviews on surgical and conservative treatments from an evidence-based approach

Introducción. Alrededor del 70-80% de la población presentará dolor de espalda incapacitante algún momento en su vida como consecuencia de la Enfermedad Degenerativa Espinal (EDE). Los costes globales que genera la enfermedad se estiman en torno al 1-2% del PIB anualmente. Desde el punto de vista de la Medicina Basada en la Evidencia (MBE), se constata una llamativa discrepancia entre la enorme disponibilidad y creciente uso de técnicas quirúrgicas (en especial de fusión espinal) y la escasa evidencia científica que apoya su utilización. Material y métodos. Hemos revisado cuidadosamente todos los metaanálisis referentes a tratamientos de la EDE publicados hasta Diciembre de 2003 y hemos clasificado las recomendaciones terapéuticas en niveles de evidencia (fuerte, moderada, limitada o ausencia de evidencia), tanto para tratamientos quirúrgicos como conservadores, siguiendo las pautas de la MBE. Resultados. Identificamos 44 metaanálisis de interés (9 sobre cirugía lumbar, 3 sobre cirugía cervical y 32 sobre otros tratamientos). Desde el punto de vista quirúrgico, sólo alcanza nivel de evidencia fuerte la laminectomía precoz en síndrome de cola de caballo por extrusión discal; la superioridad de la discectomía simple o microdiscectomía frente a quimionucleolisis en prolapso discal y espondilosis; y la cirugía de fusión (en principio, no instrumentada) en espondilolistesis ístmica del adulto o degenerativa asociada a estenosis lumbar. En espondilosis cervical con radiculo y/o mielopatía cervical leve, la discectomía más fusión no supera a la discectomía simple y ésta es dudosamente superior a la historia natural de la enfermedad más allá de 24 meses. La utilización profiláctica de antibióticos en cirugía espinal es beneficiosa. No se demuestra beneficio de la cirugía en dolor discogénico. Ninguna terapia conservadora alcanza el nivel de evidencia fuerte. Los antidepresivos mejoran la percepción del dolor pero no la funcionalidad. Discusión. A pesar de que se ha doblado el porcentaje de cirugías de instrumentación lumbar en las últimas dos décadas y crece a un ritmo del 20% anual, no se ha demostrado de forma fehaciente una mejoría en los resultados clínicos ni siquiera en las tasas globales de artrodesis. Este llamativo incremento del uso de la cirugía en procesos diferentes a las deformidades espinales y espondilolistesis aisladas o acompañadas de estenosis del canal lumbar, quizá obedece a múltiples factores técnicos y clínico-epidemiológicos donde no podemos obviar la enorme trascendencia económica que subyace. Resulta crucial diferenciar qué subgrupos de pacientes con EDE se benefician claramente de la cirugía. Desde el punto de vista ético empieza a plantearse la necesidad de diseñar ensayos clínicos que incorporen placebos quirúrgicos, dada la escasa evidencia científica que apoya la cirugía espinal a día de hoy. La mayor parte de los tratamientos conservadores tienen una eficacia moderada o leve (casi siempre transitoria) y, probablemente, deban utilizarse en combinación. Conclusiones. La cirugía de la EDE se asienta sobre pilares inseguros habida cuenta de que la mayor parte de las técnicas que se indican no están avaladas por recomendaciones de primera clase en términos de MBE. Parece necesario consensuar, desde las organizaciones que estudian la columna degenerativa, guías de práctica clínica en lo referente al tratamiento integral y multidisciplinado de la EDE, a sabiendas que, hasta hoy, pocos tratamientos alteran de forma positiva y duradera la historia natural de la enfermedad

Introduction. The lifetime prevalence of invalidating back pain in general population caused by Spinal Degenerative Disease (SDD) is about 70-80%. Global costs related to this disease are enormous (1-2% gross domestic product). From an Evidence-based point of view, there is a striking discrepancy between the use of many available surgical techniques (especially for spinal fusion) and the lack of scientific support. Methods. The authors carefully reviewed all published metaanalysis on SDD therapies up to December 2003. Treatment recommendations were classified according to levels of evidence (strong, moderate, mild or lack of evidence) for both surgical and conservative measures. Results. Forty-four metaanalysis were selected (nine on lumbar surgery, three on cervical surgery and thirty-two on other therapies). Relating surgery, there is strong evidence favouring early laminectomy in cauda equina syndrome secondary to lumbar disc herniation; discectomy or microdiscectomy are superior to chemo-nucleolysis in lumbar prolapse and spondylosis; and fusion surgery (probably noninstrumented) in adult isthmic spondylolysthesis or degenerative spondylolysthesis with spinal stenosis. In cervical spondylosis and radiculomyelopathy, discectomy seems as efective as discectomy plus fusion, which does not seem to be better than untreated SDD beyond 24 months. Preoperative antibiotics seem to prevent infection in spinal surgery. No benefit of surgery is demonstrated in discogenic pain. None of conservative therapies are supported by strong evidence. Antidepressants improve pain perception but do not influence the functional status. Discussion. Although lumbar instrumented surgery has nearly doubled over two decades and the anual growth is about 20%, clinical results do not seem to have improved, not even global fusion rates. The increasing use of fusion surgery for cases other than spinal deformities, spondylolysthesis or spinal stenosis plus lysthesis may be related to multiple technical and clinical-epidemiological factors where huge financial and commercial interests must be considered. It is crucial to differenciate subsets of patients prone to beneft from surgery. It is discussed whether randomized trials incorporating sham operations are ethically justifiable, because of the lack of sould evidence for many spinal procedures. The efficacy of most conservative treatments is mild or moderate (mainly transient) and they should be probably used in combination. Conclusions. There is no strong evidence favouring most of surgical procedures for SDD from an evidence-based approach. It seems neccessary that scientific organizations studying SDD create clinical guidelines relating its multidisciplinary and integral management, recognizing that, up to now, few interventions positively modify in the long-term the natural history of the disease