Teresa Pujol

Prognostic Significance of O6-Methylguanine-DNA Methyltransferase Determined by Promoter Hypermethylation and Immunohistochemical Expression in Anaplastic Gliomas

Purpose: Anaplastic gliomas constitute a heterogeneous group of tumors with different therapeutic responses to adjuvant chemotherapy with alkylating agents. O6-Methylguanine-DNA methyltransferase (MGMT), a DNA repair protein, is one of the implicated factors in glioma chemoresistance.The prognostic value of MGMT remains controversial due in part to the fact that previous published studies included heterogeneous groups of patients with different tumor grades. The aim of this study was to evaluate the prognostic significance of MGMT in patients with anaplastic glioma. Experimental Design: Ninety-three patients with anaplastic glioma were analyzed for MGMT protein expression by immunohistochemistry. In addition, for those patients from whom a good yield of DNA was obtained (n = 40), MGMT promoter methylation profile was analyzed by methylation-specific PCR. MGMT prognostic significance was evaluated together with other well-known prognostic factors. Results: Fifty-one tumors (54.8%) showed nuclear staining of MGMT. There was a trend towards longer overall survival for those patients with negative MGMT immunostaining (hazard ratio, 1.66; P = 0.066). In a secondary analysis including those patients who actually received chemotherapy (n = 72), the absence of MGMT expression was independently associated with better survival (hazard ratio, 2.12; P = 0.027). MGMT promoter methylation was observed in 50% of the analyzed tumors. No statistical correlation between MGMT expression and MGMT promoter hypermethylation was observed. Conclusions: Unlike previous studies, we did not find a correlation between MGMT promoter methylation and survival. However, we observed a correlation between MGMT protein expression and survival in those patients who received chemotherapy thus suggesting that the absence of MGMT expression is a positive predictive marker in patients with anaplastic glioma.

Neurocisticercosis: ¿una enfermedad importada?

Fundamento La neurocisticercosis es una afeccion del sistema nervioso central causada por la larva del helminto Taenia solium, y representa la parasitacion cerebral mas frecuente. Es una zoonosis cosmopolita, endemica en paises de bajo nivel socioeconomico. En el presente trabajo se analizan el origen geografico y las caracteristicas clinicas de los pacientes, y se revisan las modalidades diagnosticas y el tratamiento de esta enfermedad. Pacientes y metodo Revision de las historias clinicas de los pacientes diagnosticados de neurocisticercosis desde enero de 1990 a marzo de 2000. Resultados Se incluyeron 10 pacientes, 9 de los cuales eran inmigrantes o habian viajado a paises de America Central y Sudamerica (7 pacientes), Africa (1) y sudeste asiatico (1), y tan solo un caso se origino en Espana. Nueve pacientes presentaron crisis convulsivas, en 7 de ellos en forma de crisis tonico-clonicas generalizadas, y tres casos sufrieron cefalea. En tres pacientes se obtuvo el diagnostico por biopsia cerebral o de nodulos subcutaneos, y en el resto por tomografia computarizada y/o resonancia magnetica cerebral, y serologia. La positividad de la serologia mediante ELISA fue del 60%. Ocho pacientes fueron tratados unicamente con prazicuantel o albendazol, con buena evolucion. Conclusion La neurocisticercosis es una infeccion prevalente entre la poblacion inmigrante, y en Espana la infeccion importada suele proceder de America Latina. El diagnostico se realiza por metodos de imagen cerebral y tecnicas serologicas (EITB). El tratamiento con prazicuantel o albendazol mejora la evolucion y el control de las crisis convulsivas.

Generalised dystonia with an abnormal magnetic resonance imaging signal in the basal ganglia: A case of adult-onset GM1 gangliosidosis†

We describe a 46‐year‐old woman with adult‐onset generalised dystonia and a severe speech disorder with an abnormal magnetic resonance imaging signal in the basal ganglia. A storage disease study demonstrated the presence of a GM1 gangliosidosis. This rare condition should be investigated in cases of generalised dystonia, especially in those cases with other features suggesting symptomatic dystonia.

Fiabilidad del navegador en la colocación de tornillos pediculares toracolumbares

Summary Introduction. Computer image guidance is one of the most signiicant technologic advancements in the spine surgery, because preoperative or intraoperative images can be used for multiplanar, three-dimensional intrao- perative navigation. Material and methods. We performed a prospective clinical study to assess the accuracy of pedicle screw insertion using an optoelectronic navigation system (SurgiGATE Spine 2.1 Medivision). The study popula- tion included 29 patients with diverse disorders of the thoraco- lumbar spine (degenerative 54%, spondylolis- thesis 21%, fractures 14%, scoliosis 7% and spondylo- discitis 4%). One patient was excluded from the study because problems with the speciic instruments or the computer system. Pre and post-operative axial compu- ted tomography images were obtained for each patient and analyzed by two independent radiologists to place- ment accuracy. The correct location was deined accord to Heary scale in 5 grades. Results. 163 image-guided thoraco-lumbar pedicle screws were placed 29 in the thoracolumbar spine and 134 in the lumbosacral spine. We achieved a completely intraosseous placement (Grade I) in 99.4% of lumbo- sacral spine screws and 100% of thoracolumbar spine screws. Only one misplaced screw (Grade III) in the pedicle of L III in the concavity of a scoliosis was repor- ted. No implant related complications were noted. Conclusions. The low rate of misplaced screws in this prospective study compares favorably with previo- usly published results. Our initial results indicate that Image-guided spinal surgery is a safe technique which improves surgical performance during posterior trans- pedicle stabilization.

T2 hypointense rims and ring-enhancing lesions in MS

Background: Hypointense rims peripherally on T2-weighted MRI (rim lesions) have been associated with gadolinium ring-enhancing lesions in multiple sclerosis (MS) in pathological studies. However, little is known about their frequency, we analyzed clinical significance in a cohort of MS sufferers according to routine clinical practice. Methods: We retrospectively reviewed all available MRI scans performed on our MS patients between 2000 and 2009. A total of 580 MRI scans from 257 patients were analyzed. The presence of rim lesions and ring enhancement was assessed and counted blind. Furthermore, the correlation between both patterns, and with clinical characteristics, was evaluated. Results: Thirty-five rim lesions were identified and 9% (24/257) of the patients showed at least one of these lesions. Forty ring-enhancing lesions were counted and 12% (29/245) of the patients who had undergone gadolinium MRI presented at least one such lesion. Thirteen lesions co-localized both patterns (40% of the rim lesions and 33% of the ring-enhancing lesions). Rim lesions and ring-enhancing lesions were observed in patients with clinically isolated syndrome (7%, 7%), relapsing—remitting (11%, 15%) and secondary progressive (13%, 9%) but none with primary progressive MS. Presence of ring-enhancing lesions was significantly associated with a shorter time to reach EDSS (Expanded Disability Status Scale) 4.0 and 6.0 (hazard ratio 7.6, 95% confidence interval 2.3—24.6). Conclusions: Rim lesions and ring-enhancing lesions are present in close to 10% of patients with MS, and frequently both lesions appear independently one to the other. The association of ring enhancement with worst prognosis needs to be confirmed in prospective studies.

Secondary orbital metastases from cutaneous melanoma.

Secondary orbital melanomas comprise a heterogeneous group of malignant pigmented tumours. They may present as extrascleral extensions of uveal melanomas, as orbital extensions of conjunctival and eyelid melanomas, as local recurrences after surgical or conservative treatment of ocular melanomas, or as orbital metastases from distant cutaneous melanomas. The differential diagnosis of an orbital sign such as an intraconal mass or enlargement of one or more extraocular muscles includes myositis, Graves’ disease, pseudotumour, trichinosis, Cryptococcus, arteriovenous malformation, carotid cavernous fistula, acromegaly, amyloidosis, lymphomas and other primary neoplasms [2,3].

Does gender matter in glioblastoma

BackgroundThe clinical outcome of glioblastoma (GBM) patients who receive radiotherapy alone or with chemotherapy is well established. However, little is known about how many patients do not receive this treatment. We consider it is important to investigate why a proportion of operated patients do not receive further treatment after surgery.MethodsWe reviewed all consecutive GBM patients operated on in our hospital between January 2000 and December 2008.ResultsA total of 216 patients with GBM were identified. Fifty-five (25%) did not receive any treatment after surgery. Univariate analysis showed that factors associated with no further treatment after surgery were older than 60 years (p=0.002), of female gender (p=0.03), had a KPS<70 (p<0.001) and had had a biopsy (p<0.001). Multivariate analysis indicated that age ≥60 years and KPS <70 were independent predictors of no further treatment after surgery. Gender was not an independent variable. However, women in the whole series were older than 60 years (p=0.01), and they had a worse KPS (p=0.02) and more biopsies (p=0.04) than men. In the whole group, median survival time was 10.4 months for men (n=125) vs. 7.2 months for women (n=91), log rank p<0.04. This difference was not observed in the group that was treated after surgery.ConclusionsOne out of four patients could not be treated after surgery. Independent predictors were older age and low KPS. These poor risk variables were more frequent in women and their survival was therefore lower than men in our series.

Pseudoprogression as an adverse event of glioblastoma therapy

We explored predictive factors of pseudoprogression (PsP) and its impact on prognosis in a retrospective series of uniformly treated glioblastoma patients. Patients were classified as having PsP, early progression (eP) or neither (nP). We examined potential associations with clinical, molecular, and basal imaging characteristics and compared overall survival (OS), progression‐free survival (PFS), post‐progression survival (PPS) as well as the relationship between PFS and PPS in the three groups. Of the 256 patients studied, 56 (21.9%) were classified as PsP, 70 (27.3%) as eP, and 130 (50.8%) as nP. Only MGMT methylation status was associated to PsP. MGMT methylated patients had a 3.5‐fold greater possibility of having PsP than eP (OR: 3.48; 95% CI: 1.606–7.564; P = 0.002). OS was longer for PsP than eP patients (18.9 vs. 12.3 months; P = 0.0001) but was similar for PsP and nP patients (P = 0.91). OS was shorter–though not significantly so—for PsP than nP patients (OS: 19.5 vs. 27.9 months; P = 0.63) in methylated patients. PPS was similar for patients having PsP, eP or nP (PPS: 7.2 vs. 5.4 vs. 6.7; P = 0.43). Neurological deterioration occurred in 64.3% of cases at the time they were classified as PsP and in 72.8% of cases of eP (P = 0.14). PsP confounds the evaluation of disease and does not confer a survival advantage in glioblastoma.

Increased signal intensity in FLAIR sequences in the resection cavity can predict progression and progression-free survival in gliomas

OBJECTIVE To determine if hyperintense fluid in the postsurgical cavity on follow-up fluid-attenuated inversion recovery (FLAIR) sequences can predict progression in gliomas. MATERIAL AND METHODS Observational study of magnetic resonance imaging signal of fluid within the post-surgical cavity in patients with glioma (grade II-IV), with surgery and follow-up between 2007 and 2012. Qualitative comparison between the signal of fluid in the cavity and of the ventricular cerebrospinal fluid (CSF) was performed on FLAIR sequences. Fluid in the cavity was classified as isointense or hyperintense compared to CSF. Double-blind reading was performed. The signal intensity was correlated with tumour progression, assessed using Response Assessment in Neuro-Oncology criteria. RESULTS A total of 107 patients were included, of whom 90 had high-grade gliomas. Inter-rater agreement was excellent, and intra-rater complete (k=0.94 and 1, p<.001). Hyperintense fluid in the resection cavity occurred more commonly (58.9% versus 29.4%, p=.025) and earlier (mean 4.5 versus 9.9 months, p<.001) in high-grade than in low-grade gliomas. Hyperintense fluid was associated with progression in high-grade gliomas, with a sensitivity of 65.7% (95%CI, 54.3-75.6%) and a specificity of 70.6% (95%CI, 46.6-87%), and in low-grade gliomas with a sensitivity of 50% (95%CI, 18.7-81.2%), and a specificity of 81.8% (95%CI, 51.1-96%). The positive predictive value of this sign was 90.6% (95%CI, 79.3-96.3%) for high-grade gliomas, and was higher for grade IV (93.2%, 95%CI, 87.3-99.1%) and lower for grade III (77.8%, 95%CI, 59.6-96%), and low-grade gliomas (60%, 95%CI, 22.9-88.4%). False-positives were identified in 7 patients, due to bleeding or infection. Hyperintense fluid in high-grade gliomas preceded progression in 22 patients (30.1%), with a mean of 4.1 months (SD 2.1, 95% CI, 3.2-5), and associated with poorer progression-free survival (mean 6.8 versus 11.7 months, p=.004). CONCLUSIONS Hyperintense fluid in the resection cavity on follow-up FLAIR sequences occurs more frequently and earlier in high-grade gliomas, and is associated with poorer progression-free survival. Hyperintense fluid is associated with disease progression, and can predict the progression of resected gliomas. False-positives due to bleeding and infection can be observed, and are easily recognizable.

Left hemibody myoclonus due to anomalous right vertebral artery

A 43‐year‐old man presented with sporadic, sudden, brief, and involuntary jerks of his left limbs and trunk muscles. The electromyographic recordings showed short‐lasting highly synchronized bursts, compatible with myoclonus limited to the left hemibody. Blink reflex, masseter silent period, cortical and spinal magnetic stimulation, somatosensory cortical evoked potentials, and electroencephalogram (EEG) were normal; the EEG back‐averaging showed no spikes preceding the myoclonus. Magnetic resonance imaging and magnetic resonance angiography showed the presence of an anomalous nonectasic right vertebral artery compressing the right side of ventral medulla oblongata. We hypothesize that the aberrant right vertebral artery induced abnormal activation of descending motor tracts responsible for the myoclonus.