Critical Evaluation of the Scientific Literature Concerning Bone Graft Alternatives in Spinal Surgery and Focus on Bioceramics.

To improve solid spinal fusion while avoiding the morbidity associated with autograft harvesting procedures, numerous alternatives have been investigated, including allograft, demineralized bone matrix (DBM), cell-based therapies and growth factors (i.e., bone morphogenetic proteins, platelet concentrates), and ceramic-based biomaterials. Even though all of these approaches have the potential to improve the outcome of spinal fusion procedures, most of them have not yet been validated by evidence-based clinical results, and thus they are not strongly advisable for clinical use, in addition to being particularly expensive. Here, we give an overview of the current clinical evidence for bone graft alternatives for spine surgery procedures. We will also evaluate the pros and cons of their use and briefly review the more relevant literature.

Calcified brain metastases may be more frequent than normally considered.

OBJECTIVES: To verify the incidence of calcified brain metastases (CBM), illustrating the different presentation patterns and histology of primary tumor. METHODS: A series of 1002 consecutive brain computed tomography (CT) scans of patients with known primary tumors was retrospectively assessed. CBM were defined by the presence of calcification within intra-axial-enhancing lesions; identification of CBM was based on visual examination and ROI analysis (> 85 Hounsfield units). Also, calcifications in the primary tumor of all patients with brain metastases were evaluated. In CBM patients, we investigated the type of calcifications (punctate, nodular, cluster, ring, coarse), the histology of primary tumor, and if a previous RT was performed. RESULTS: Among 190 (18.9%) patients with brain metastatic disease, 34 presented with CBM (17.9%). Sixteen patients were previously treated with RT, while 18 presented calcifications ab initio (9.5% of all brain metastases). The majority of patients with CBM had a primitive lung adenocarcinoma (56%), followed by breast ductal invasive carcinoma (20%) and small cell lung carcinoma (11.8%). CBM were single in 44.1% of patients and multiple in 55.9%. With regard to the type of calcifications, the majority of CBM were punctate, without specific correlations between calcification type and histology of primary tumor. No patients with ab initio CBM had calcifications in primary tumor. CONCLUSION: In conclusion, our data show that CBM are more common than usually thought, showing an incidence of 9.5% ab initio in patients with brain metastases. This study underlines that neuroradiologists should not overlook intraparenchymal brain calcifications, especially in oncologic patients. KEY POINTS: • Among the differential diagnosis of brain intraparenchymal calcifications, metastases are considered uncommon and found predominantly in patients treated with radiotherapy (RT). • Our data show that CBM are more common than usually thought, showing an incidence of 9.5% ab initio in patients with brain metastases. • A proportion of intraparenchymal brain calcifications, especially in oncologic patients, might represent evolving lesions and neuroradiologists should not overlook them to avoid a delay in diagnosis and treatment.

Acute neurologic decline in a patient with spinal stenosis: blame it on the epidural fat.

Spinal epidural lipomatosis [SEL] is defined as an excessive accumulation of extradural normal adipose tissue. This condition may be idiopathic or acquired. Surgical decompression is considered the gold standard treatment in patients presenting with progressive neurologic deficit. We report a case of a 69-year-old male patient presented with neurogenic claudication and lower left limb radiculopathy. The magnetic resonance imaging (MRI) revealed a L5-S1 epidural compression sustained by a large epidural plaque whose signal was consistent with adipose tissue. A conservative approach, including weight loss attempt, revealed unsuccessful and the patient presented some months after the diagnosis at the emergency department with acute onset bilateral drop foot, more severe on the right side and urinary disturbances. Microsurgical decompression via L5 laminectomy and partial L4 laminectomy and fatty plaque debulking was performed. The post operative course was uneventful and at the two months post operative follow up the patient reported a significative improvement of the pre operative neurological signs and symptoms and of pain control. SEL deserves attention as an identifiable cause of radiculopathies, typically attributed to spinal stenosis, with a higher incidence than previously reported. Moreover cases of acute onset of cauda equina like syndrome were reported in patent affected by SEL, probably related to a local venous engorgement with stasis and edema. Therefore it should be considered as a possible diagnosis not only in patients complaining of stenosis-type symptoms but also in cases of acute neurological decline with cauda equina like syndrome, especially when provided with a "benign" imaging reading.

Giant tuberculoma of the corpus callosum, the unforeseen diagnosis.

OBJECTIVE: Isolated intracranial tuberculomas are rare, especially in adults and it is not uncommon that they are easily confused with other diseases. To address this issue, we reported a case of a tuberculoma of the corpus callosum focusing on clinical characteristics, diagnostic clues, and outcome. CONCLUSIONS: Intracranial masses are frequently targeted as neoplastic pathology with surgical treatment in most cases. It is important to distinguish between neuro tuberculoma and brain tumors because of their different management and prognosis. Therefore even in absence of a known history of primary TB and in immunocompetent patients, tuberculoma must be in the differential diagnosis of solitary intracranial lesions also in countries where TB is not endemic.

Brain positron emission tomography in idiopathic normal-pressure hydrocephalus: new 18 F-fluorodeoxyglucose pattern in a long-known syndrome.

AIM: Patients with idiopathic normal-pressure hydrocephalus (iNPH) can show a global reduction in cerebral glucose metabolism at [ 18 F]Fluorodeoxyglucose (FDG) PET. The presence of caudate hypometabolism has been identified as a potential biomarker in iNPH, yet there is limited evidence of hypermetabolic findings in patients with iNPH so far. METHODS: We retrieved retrospectively patients with iNPH and normal cognitive assessment, evaluated before surgery undergoing brain [ 18 F]FDG-PET. The 18 F-FDG-PET brain scans were compared to those of a control group of healthy subjects, matched for age and sex, by statistical parametric mapping (SPM) to identify areas of relative hypo- and hypermetabolism. Furthermore, the existence of a correlation between areas of hypo- and hypermetabolism in the patient group was tested. RESULTS: Seven iNPH patients (mean age 74 ±â€…6 years) were found in the hospital database. SPM group analysis revealed clusters of significant hypometabolism ( P  = 0.001) in the iNPH group in the dorsal striatum, involving caudate and putamen bilaterally. Clusters of significant hypermetabolism ( P  = 0.001) were revealed in the bilateral superior and precentral frontal gyrus (BA 4, 6). A significant inverse correlation between striatal hypometabolism and bilateral superior and precentral frontal gyrus hypermetabolism was revealed ( P  < 0.001 corrected for multiple comparisons). CONCLUSION: In this cohort, patients with iNPH showed subcortical hypometabolism, including bilateral dorsal striatum. To the best of our knowledge, this is the first report demonstrating a hypermetabolic pattern in the primary motor and premotor areas, and showing an inverse correlation between the striatum and motor cortex in patients with iNPH.

Gamma knife radiosurgery for cerebral arteriovenous malformations in children/adolescents and adults. Part I: Differences in epidemiologic, morphologic, and clinical characteristics, permanent complications, and bleeding in the latency period.

PURPOSE: To compare the epidemiologic, morphologic, and clinical characteristics of 92 children/adolescents (Group A) and 362 adults (Group B) with cerebral arteriovenous malformations (cAVMs) considered suitable for radiosurgery; to correlate radiosurgery-related permanent complication and post-radiosurgery bleeding rates in the 75 children/adolescents and 297 adults available for follow-up. METHODS AND MATERIALS: Radiosurgery was performed with a model C 201-source Co60 Leksell Gamma Unit (Elekta Instruments, Stockholm, Sweden). Fisher exact two-tailed, Wilcoxon rank-sum, and two-sample binomial exact tests were used for statistical analysis. RESULTS: There were significant differences between the two populations in sex (p = 0.015), clinical presentation (p = 0.001), and location (p = 0.008). The permanent complication rate was lower in younger (1.3%) than in older patients (5.4%), although the difference was not significant (p = 0.213). The postradiosurgery bleeding rate was lower in Group A (1.3%) than in Group B (2.7%) (p = 0.694), with global actuarial bleeding rates of 0.56% per year and 1.15% per year, respectively. CONCLUSIONS: The different characteristics of child/adolescent and adult cAVMs suggest that they should be considered two distinct vascular disorders. The similar rates of radiosurgery-related complications and latency period bleeding in the two populations show that gamma knife radiosurgery does not expose young patients to a higher risk of sequelae than that for older patients.

Gamma Knife radiosurgery for cerebral arteriovenous malformations in children/adolescents and adults. Part II: Differences in obliteration rates, treatment-obliteration intervals, and prognostic factors.

PURPOSE: To evaluate and compare obliteration rates (OBRs) and treatment-obliteration intervals (TOIs) for cerebral arteriovenous malformations (cAVMs) treated with Gamma Knife radiosurgery in children/adolescents and adults; and to determine factors predicting the OBR and TOI in these two populations. METHODS AND MATERIALS: This study concerned 62 children/adolescents and 193 adults observed for > or = 3 years. Fisher exact two-tailed and Wilcoxon rank-sum tests, multiple logistics, and Cox proportional hazard models were used for statistical analysis. RESULTS: The overall OBR was 85.5% in children/adolescents and 87.6% in adults (p = 0.671), but children/adolescents showed higher 36-month actuarial OBRs (69.35%) and shorter median TOIs (25.7 months) than adults (66.84% and 28.2 months; p = 0.006 and p = 0.017, respectively). In children/adolescents, lower Spetzler-Martin grades (p = 0.043) and younger age (p = 0.019) correlated significantly with OBRs, and lower Spetzler-Martin grades (p = 0.024) and noneloquent cAVM locations (p = 0.046) with TOIs. In adults, low flow through the cAVM and < 6.2-cm3 volume were associated with both OBR and TOI (p = 0.012 and p = 0.002, respectively). CONCLUSIONS: The differences in OBRs within 3 years and TOIs, although slight, seem to show that pediatric cAVMs behave differently from those in adults after Gamma Knife radiosurgery.

Significant prevalence of antibodies reacting with simian virus 40 mimotopes in sera from patients affected by glioblastoma multiforme.

BACKGROUND: Glioblastoma multiforme (GBM) is a rare tumor, which affects 1/100 000 individuals, but it represents 30% of central nervous system malignancies. GBM is a severe tumor responsible for 2% of all cancer-related deaths. Although characterized by genotypic and phenotypic heterogeneities, GBM invariably resists conventional chemo- and radiotherapies. Several chromosome alterations and gene mutations were detected in GBM. Simian virus 40 (SV40), a small DNA tumor virus, has been found in GBM specimens by some studies, while other investigations have not confirmed the association. METHODS: An indirect enzyme-linked immunosorbent assay with 2 synthetic peptides mimicking SV40 antigens of viral capsid proteins 1-3 was employed to detect specific antibodies against SV40 in serum samples from GBM-affected patients, together with controls represented by patients affected by breast cancer and normal subjects of the same median age. RESULTS: Our data indicate that in serum samples from GBM-affected patients (n = 44), the prevalence of antibodies against SV40 viral capsid protein antigens is statistically significantly higher (34%, P = .016 and P = .03) than in the control groups (15%), represented by healthy subjects (n = 101) and patients affected by breast cancer (n = 78), respectively. CONCLUSION: Our data indicate that SV40, or a closely related yet undiscovered human polyomavirus, is associated with a subset of GBM and circulates in humans. Our study can be transferred to the clinical oncology application to discriminate different types of heterogeneous GBM, which in turn may address an innovative therapeutic approach to this fatal cancer.

Long-term tumor control of benign intracranial meningiomas after radiosurgery in a series of 4565 patients.

BACKGROUND: Radiosurgery is the main alternative to microsurgical resection for benign meningiomas. OBJECTIVE: To assess the long-term efficacy and safety of radiosurgery for meningiomas with respect to tumor growth and prevention of associated neurological deterioration. Medium- to long-term outcomes have been widely reported, but no large multicenter series with long-term follow-up have been published. METHODS: From 15 participating centers, we performed a retrospective observational analysis of 4565 consecutive patients harboring 5300 benign meningiomas. All were treated with Gamma Knife radiosurgery at least 5 years before assessment for this study. Clinical and imaging data were retrieved from each center and uniformly entered into a database by 1 author (A.S.). RESULTS: Median tumor volume was 4.8 cm³, and median dose to tumor margin was 14 Gy. All tumors with imaging follow-up < 24 months were excluded. Detailed results from 3768 meningiomas (71%) were analyzed. Median imaging follow-up was 63 months. The volume of treated tumors decreased in 2187 lesions (58%), remained unchanged in 1300 lesions (34.5%), and increased in 281 lesions (7.5%), giving a control rate of 92.5%. Only 84 (2.2%) enlarging tumors required further treatment. Five- and 10-year progression-free survival rates were 95.2% and 88.6%, respectively. Tumor control was higher for imaging defined tumors vs grade I meningiomas (P < .001), for female vs male patients (P < .001), for sporadic vs multiple meningiomas (P < .001), and for skull base vs convexity tumors (P < .001). Permanent morbidity rate was 6.6% at the last follow-up. CONCLUSION: Radiosurgery is a safe and effective method for treating benign meningiomas even in the medium to long term.

Leksell gamma knife radiosurgery for cerebral arteriovenous malformations in pediatric patients.

OBJECTS: The authors report their experience of gamma knife radiosurgery (GKR) in a large series of pediatric cerebral arteriovenous malformations (cAVMs). The advantages, risks and failures of this approach are presented and discussed. METHODS: Gamma knife radiosurgery was performed on 63 children aged < or =16 years. Haemorrhage was the clinical onset in 50 out of 63 cases. The mean pre-GK cAVM volume was 3.8 cm(3). Fifty-eight out of 63 cAVMs were Spetzler-Martin grades I-III. Most lesions (47 out of 63) were in eloquent or deep-seated brain regions. CONCLUSION: Gamma knife radiosurgery-related complications occurred in 2 out of 47 cases with an available follow-up (1 had transient and 1 permanent morbidity). No bleeding occurred during the latency period. In 39 children with >36-month follow-up, complete cAVM occlusion was angiographically documented in 31, with a 3- and 4-year actuarial obliteration rate of 72 and 77% respectively. High rates of complete obliteration and very low frequency of permanent morbidity with no bleeding during the latency period encourage widespread application of GKR in the treatment of pediatric cAVMs.