Konstantinos S. Polyzoidis

Cauda equina paraganglioma: a review

Although rare, cauda equina paraganglioma (CEP) is definitely established in the table of cauda equina tumours. There are no particular investigations to document its preoperative diagnosis, unless a vasomotor amine syndrome is present to guide the differential diagnostic spectrum. Magnetic resonance imaging is the examination of choice for the presurgical assessment, but there are still overlapping findings, mainly among CEP, ependymoma, schwannoma, and hemangioblastoma. It is also the only means for postoperative follow-up. Computed tomography may fail to reveal all intrathecal lesions. Total excision is the gold standard for lesions with such a benign or at least protracted clinical course, as observed with the CEP. In contrast to well-known oncologic principles in micro, ultrastructural, and immunohistochemical prediction analysis, these tumours behave in an independent fashion. Promising efforts are being conducted in immunohistochemistry and DNA search, but the mainstay of our knowledge regarding its natural history still stems from our sporadic observation of its clinical behaviour.

Evaluation of meningioma aggressiveness by 99mTc-Tetrofosmin SPECT

OBJECTIVES Although meningiomas usually have a benign clinical course, atypical and malignant types of this brain tumor are associated with high recurrence rates and poor outcome; thus, DNA ploidy and S-phase -- as determined by DNA flow cytometry -- are useful indicators of their biological behavior. Brain single-photon emission computed tomography (SPECT) has been suggested as a potentially useful modality for the metabolic assessment of various brain tumors. This study evaluated whether (99m)Tc-Tetrofosmin ((99m)Tc-TF) uptake correlates with meningioma proliferative activity, as assessed by flow cytometry analysis. PATIENTS AND METHODS Ten consecutive patients (3 males, 7 females, mean age 64.6 years) with a diagnosis of a symptomatic intracranial meningioma, planned to undergo surgery, were studied. Brain SPECT by (99m)Tc-TF was performed within a week prior to surgical excision and flow cytometric analysis was performed in the excised tissue. Tumoral radiotracer accumulation was first assessed visually. Semiquantitative image analysis was also performed, by calculating the lesion-to-normal (L/N) uptake ratio. RESULTS Benign meningiomas were diagnosed in 8/10 cases, the remaining 2/10 patients had anaplastic lesions. DNA aneuploidy was found in 2 lesions, the remaining tumors were diploid. There was a significant correlation between tracer uptake and the percentage of the cell fraction on S-phase (r=0.733, P=0.05). There was also a positive correlation between tracer uptake and the level of aneuploidy and tumor grade. CONCLUSION These results imply that (99m)Tc-TF brain SPECT may have the ability to discriminate benign meningiomas from malignant meningiomas pre-operatively, the tracer uptake being a likely indicator of their proliferative activity.

Evaluation of glioma proliferation by 99mTc-Tetrofosmin

The proliferation potential of gliomas is an indicator of their aggressiveness with significant implications in patient management and prognosis, but its assessment requires tissue sampling.1 We evaluated the relationship between glioma proliferation (as expressed by the Ki-67 index) and the uptake of the tumor-seeking radiotracer technetium-99m Tetrofosmin (99mTc-TF). Fourteen patients with a space-occupying lesion suspicious for glioma on structural brain imaging were prospectively enrolled. Scintitomographic (SPECT) imaging was performed and within a week the lesion was removed surgically; Ki-67 was assessed in the excised specimens by MIB-1 immunostaining. Three patients were excluded from the study because their lesions were proven metastatic. In the 11 patients eligible for analysis (7 males, 4 females; mean age 49.5 ± 7.5 years), the diagnosis was glioblastoma multiforme (6 cases), anaplastic astrocytoma (1), anaplastic oligodendroglioma (2), low-grade oligodendroglioma (1), and low-grade astrocytoma (1). We found a significant positive linear correlation between 99mTc-TF uptake and Ki-67 expression (r = 0.95, p = 0.001 [Spearman rank analysis]; Fig. 1 – 3). No significant correlation was observed between tracer uptake and tumor grade (r = 0.27, p = 0.420). The preliminary results of this pilot study, although deriving from a limited patient sample, propose that this tracer may hold a potential role as a noninvasive marker of glioma proliferative activity. Figure 1 T1-weighted, gadolinium-enchanced MRI (A) in a low-grade oligodendroglioma of the left frontal lobe. Faint 99mTc-Tetrofosmin uptake (B, arrow) correlated with Ki-67 approx. 2% (C; MIB-1 ×100). Figure 3 Correlation between 99mTc-Tetrofosmin uptake (expressed as lesion-to-normal [L/N] uptake ratio) and cellular proliferation rate (MIB-1) in the studied gliomas.

Frequent abnormalities of the immune system in gliomas and correlation with the WHO grading system of malignancy

AIM To investigate the cellular and humoral immunity status of gliomas, and their association with the WHO grading system. MATERIAL AND METHODS We have conducted a case-control study of 49 patients with gliomas and 30 healthy controls. We used ELISA assays, radial immunodiffusion, indirect immunofluorescence, latex test and flow cytometry assays to estimate preoperative in serum the immunological profile. RESULTS Patients with glioma had significantly reduced amounts of IL2 (p=0.000), TNF-a (p=0.033), IgG (p=0.011), IgA (p=0.027),C4 (p=0.026) ,CD3+ (p=0.001), CD4+ (p=0.000), CD8+ (p=0.002), ratio CD4/CD8 (p=0.000), CD19+ (p=0.04) and elevated IL10 (p=0.05) compared with healthy controls. No statistically significant differences were observed concerning viral agents, total NK cells, IgM, IgE, IL16, granzyme-b, RF, ANA, ENA, anti-dsDNA and anti-cardiolipin antibodies. A higher WHO grade, after controlling for age and gender, was associated with decreased number of CD3+ (p=0.011), CD4+ (p=0.015), CD8+ (p=0.048) and ratio CD4/CD8 (p=0.027), as well as with decreased IL2 (p=0.018), C4 (p=0.02), and IgG (p=0.05). IL2 and CD4+ counts were significant predictors of grade. CONCLUSIONS A shift from Th1 to Th2, a CD3+ and CD19+ lymphocytopenia, a diminished fraction CD4/CD8 and a reduced amount of immunoglobulins and complement were observed in the patients with gliomas. A higher WHO grade of the tumor was associated with greater impairments of immunity. Since defects of both humoral and cellular immunity were equally observed and significant predictors of grade were assessed, a preoperative evaluation of the immune system of patients with gliomas is being proposed.

Descriptive Epidemiology of Cerebral Gliomas in Northwest Greece and Study of Potential Predisposing Factors, 2005–2007

Background: To investigate the epidemiologic and clinical characteristics (age, sex, tumor location, socioeconomic status) and potential predisposing factors (alcohol, tobacco, mobile phone use, severe head trauma) of cerebral gliomas in a defined area of Northwest Greece. Methods: The prospective study was conducted in patients with gliomas referred to all 7 hospitals of a study area with a population of 488,435 inhabitants, from June 1, 2005, to May 31, 2007. Incidence rates (IR) were calculated as new cases diagnosed among residents of the study area during the study period per 100,000 inhabitants. A case-control study was carried out in order to study the possible association of the risk of glioma with smoking, alcohol, use of mobile phone, and severe cranial trauma. Results: A total of 56 glioma incident cases were identified with IRs of glioma and glioblastoma (GBM) at 5.73/105/year and 3.69/105/year, respectively. A male to female ratio of 1.25 was obtained in the GBM group. IRs of glioma and GBM for both males and females were higher in the age group 60–79. The most frequent anatomic location was the frontal lobe. 46.5% of the patients originated from the low, 25% from the middle and 28.5% from the high socioeconomic class. There was no significant association between glioma and alcohol consumption, smoking and mobile phone use. A trend for a positive association between the risk of glioma and a history of severe cranial trauma was observed, but this association was not statistically significant. Conclusion: The estimated IR of glioma and GBM in this study was higher compared with data from other studies carried out on European, Asian and US populations. Further studies may be needed to assess the possible association of genetic, environmental and lifestyle factors with the high occurrence of gliomas observed in this study.

Multifocal glioblastoma with remote cutaneous metastasis: a case report and review of the literature.

BACKGROUND Remote extracranial mestastases of glioblastoma multiforme (GBM) are uncommon, while cutaneous seeding at a distance from the operative site appears to be even more unusual. CASE REPORT A 63-year-old man presented with focal seizures and mental impairment. Computed tomography (CT) scan revealed a left frontoparietal mass. He underwent a gross total removal of the tumor. The tissue diagnosis was that of a GBM. Seven months later, the patient developed a left scapular subcutaneous mass. Fine-needle aspiration cytology (FNAC) was performed and the cytological findings disclosed again a GBM. One month later, after clinical deterioration, a repeat magnetic resonance imaging (MRI) scan was carried out which demonstrated two new distinct lesions in the opposite hemisphere, as in a multifocal GBM. Both lesions were biopsed under stereotactic guidance and the recurrence of GBM was confirmed. The patient died ten months after the primary diagnosis of the intracranial GBM. CONCLUSION Improved diagnostic modalities and prolonged survival have increased the likelihood of detection of extracranial mestastases from GBM. This potential may be greater in multifocal GBM. FNA is a valuable method for the definite diagnosis of metastatic GBMs. Although several theories have been postulated, the route of remote cutaneous dissemination and the mechanism of multifocal recurrence remain to be elucidated.

Superficial siderosis of the CNS: Report of three cases and review of the literature

Superficial siderosis (SS) is a rare entity. A chronic subarachnoid hemorrhage (SAH) leads to the deposition of ferric pigments and ions in the surface of the central nervous system (CNS). The cause of this hemorrhage is identified in half of the cases. The disease progresses slowly and the damage is often irreversible by the time diagnosis is established. The management focuses on the identification and ablation of the bleeding source. Knowledge about this entity is based on sporadic reports. We describe three cases of superficial siderosis and briefly review the literature.

Tc-99m Tetrofosmin SPECT for the differentiation of a cerebellar hemorrhage mimicking a brain metastasis from a renal cell carcinoma

Dear Editor, Distinguishing neoplastic from non-neoplastic intracerebral hemorrhage is a difficult task. We evaluated the usefulness of Tc-99m Tetrofosmin brain SPECT in a patient suspected of having a neoplastic intracerebral hematoma. A 55-year old man was admitted to the hospital for a severe frontal headache of sudden onset. An emergency CT scan was performed and a hemorrhagic lesion was revealed in the left cerebellar hemisphere. The patient was hospitalized for further evaluation and treatment. Two years earlier he had undergone nephrectomy. The histological diagnosis was clear cell carcinoma. MRI brain scan was performed and showed that the lesion was hyperintense on T1 (Figure 1) and T2 weighted images, compressing the fourth ventricle and pons, and surrounded by edema. A ring enhancement was also noted after contrast administration (Figure 2). A metastatic lesion was suspected. For further investigation a brain SPECT was performed using Tc-99m Tetrofosmin. The uptake of Tc-99m Tetrofosmin was assessed visually but no area of abnormal uptake appeared in the region of interest (Figure 3). Due to the patient’s previews renal cell carcinoma the lesion was resected. Histopathologically it was proven to be hemorrhage. In average 1–3 years after nephrectomy, 3, 9–24% of patients with renal cell carcinoma experience brain metastasis [1]. Especially clear cell renal cell carcinoma has the propensity for distant metastasis from the early stage of the disease to several years [2,3]. Furthermore, metastatic brain tumors have the highest incidence of tumoral bleeding [4]. MRI cannot always distinguish between neoplastic and non-neoplastic hemorrhage due to considerable overlap between their imaging findings [5]. Tc-99m Tetrofosmin is a lipophilic diphosphine routinely used for myocardial perfusion imaging. Its whole uptake mechanism is not understood although bearing similarities to Tc-99m MIBI and depending

Randomized Trials of Neurosurgical Interventions: A Systematic Appraisal

OBJECTIVE:To systematically appraise the study design and quality of reporting of randomized controlled trials (RCTs) on neurosurgical procedures and to identify potential defects and biases. METHODS:Randomized controlled trials with at least five patients comparing any neurosurgical procedure against another procedure, nonsurgical treatment, or no treatment were retrieved from MEDLINE, EMBASE, and the Cochrane Library. We analyzed study design, quality of reporting, and trial results. RESULTS:The median sample size in the 108 eligible reports was 68 patients. Ninety-nine trials (91.7%) reported inclusion and exclusion criteria, 55 (50.9%) mentioned the randomization mode, and 87 (80.6%) adequately described withdrawals, but only 31 (28.7%) described allocation concealment, only 23 (21.3%) gave power calculations, and only 20 (18.5%) were adequately powered. Significant efficacy or trend for efficacy was claimed in 46 reports (42.6%), and no difference between the compared procedures was found in 60 trials (55.6%). Trials with a larger sample size were more likely to report withdrawals (P = 0.02) and power calculations (P = 0.006). Only 14 trials (13.6%) were double-blind, and this was less frequent in longer trials (P = 0.02). Among quality criteria, only the reporting of randomization mode improved significantly over time (P = 0.015). CONCLUSION:Several aspects of the design and reporting of randomized controlled trials on neurosurgical procedures can be improved. Larger, adequately powered, and accurately reported trials are needed.

Subependymal giant cell astrocytoma with intratumoral hemorrhage in the absence of tuberous sclerosis

Subependymal giant cell astrocytoma (SEGA) is an uncommon tumor that usually occurs in the setting of tuberous sclerosis (TS) syndrome. We report a rare case of an intratumoral and a small intraventricular hemorrhage complicating a SEGA in an adult patient without any signs of TS. Although pre-operative CT and MRI findings for the tumor were typical of SEGA, SEGA was not considered in the differential diagnosis because the patient was lacking any symptoms of TS. This is the second report of intraventricular and intratumoral hemorrhage complicating a SEGA and the first case in which these complications occurred in an adult patient in whom there was no previous suspicion of systemic disease.