Towards a common language in neurosurgical outcome evaluation: the NEON (NEurosurgical Outcome Network) proposal.

BACKGROUND: The aim of this study was to achieve a consensus on the minimum set of outcome measures and predictors to be used in the neurosurgical practice and on the timing of outcome assessment. METHODS: A consensus building approach was employed. All neurosurgical departments in Lombardy (Italy) were invited to participate by the Carlo Besta Neurologic Institute IRCCS Foundation. Three workshops were organized during which a multidisciplinary group called Neurosurgical Outcome Network (NEON) was created and the methodology to select outcome measures, predictors, and timing of outcome assessment was established. Eight working groups were created for the different neurosurgical diseases (neuro-oncological, skull base, vascular, traumatic, spinal, peripheral nervous system, malformation, functional) and 8 workshops were organized to identify the outcome measures and predictors specific for each of the neurosurgical diseases based on the experts' clinical practice and the existing literature. RESULTS: A total of 20 neurosurgical departments participated in this study. Specific outcome measures, predictors and the timing of outcome assessment were identified for each of the 8 neurosurgical diseases. Moreover, a list of variables common to all pathologies were identified by the NEON group as further data to be collected. CONCLUSIONS: A consensus on the minimum set of outcome measures and predictors and the timing of outcome assessments for 8 neurosurgical diseases was achieved by a group of neurosurgeons of the Lombardy region, called NEON. These sets could be used in future studies for a more homogeneous data collection and as a starting point to reach further agreement also at national and international level.

Relationship between lumbar lordosis, pelvic parameters, PI-LL mismatch and outcome after short fusion surgery for lumbar degenerative disease. Literature review, rational and presentation of public study protocol: RELApSE study (registry for evaluation of lumbar artrodesis sagittal alignEment).

Background: Vertebral arthrodesis for degenerative pathology of the lumbar spine still remains burdened by clinical problems with significant negative results. The introduction of the sagittal balance assessment with the evaluation of the meaning of pelvic parameters and spinopelvic (PI-LL) mismatch offered new evaluation criteria for this widespread pathology, but there is a lack of consistent evidence on long-term outcome. Methods: The authors performed an extensive systematic review of literature, with the aim to identify all potentially relevant studies about the role and usefulness of the restoration or the assessment of Sagittal balance in lumbar degenerative disease. They present the study protocol RELApSE (NCT05448092 ID) and discuss the rationale through a comprehensive literature review. Results: From the 237 papers on this topic, a total of 176 articles were selected in this review. The analysis of these literature data shows sparse and variable evidence. There are no observations or guidelines about the value of lordosis restoration or PI-LL mismatch. Most of the works in the literature are retrospective, monocentric, based on small populations, and often address the topic evaluation partially. Conclusions: The RELApSE study is based on the possibility of comparing a heterogeneous population by pathology and different surgical technical options on some homogeneous clinical and anatomic-radiological measures aiming to understanding the value that global lumbar and segmental lordosis, distribution of lordosis, pelvic tilt, and PI-LL mismatch may have on clinical outcome in lumbar degenerative pathology and on the occurrence of adjacent segment disease.

Assessment of prognostic factors in patients with metastatic epidural spinal cord compression (MESCC) from solid tumor after surgery plus radiotherapy: a single institution experience.

PURPOSE: To identify potential prognostic factors predicting functional outcome and survival after surgery followed by radiotherapy for metastatic spinal cord compression due to solid tumors. METHODS: 531 consecutive patients with metastatic epidural spinal cord compression (MESCC) were treated at our institution. Surgery followed by radiation therapy was performed in 151 patients (30%) with various histological diagnoses. Three different surgical procedures were performed: minimal resection with or without instrumented fixation, curettage, and total tumorectomy. Within 1 month after surgery, RT was performed, delivering a total dose of 30-36 Gy (3 Gy per fraction). Ten potential prognostic factors were investigated for relationship with functional outcome and survival. RESULTS: Clinical remission of pain was obtained in 91% of patients and 94 (62.5%) had recovery of neurological deficit. Recurrence in the same site of treatment occurred in nine (6%) patients. Median survival was 14 months (range 0-52 months); OS at 1, 2, and 3 years was 43.6, 37, and 21.5%, respectively. Survival was significantly associated with the histology of primary tumor (P < 0.001) and visceral metastases (P < 0.001) in the whole group; for histology, the prognostic factors statistically significant were other bone metastases in breast cancer, control of primary tumor, and the absence of visceral metastases in NSCLC and kind of surgery in the other. CONCLUSIONS: The key element for successful treatment of MESCC is multidisciplinary care of the patient, which includes all of those prognostic factors that have been, until now, analyzed and compared. In our set of patients treated for vertebral metastases, PS, time to development of symptoms, and the presence of visceral metastases affected functional outcome and survival.

Early surgical experience with minimally invasive percutaneous approach for patients with metastatic epidural spinal cord compression (MESCC) to poor prognoses.

PURPOSE: This study was designed to assess the impact of minimally invasive surgery (MIS) for the treatment of patients with metastatic epidural spinal cord compression (MESCC) and vertebral body fracture, in terms of feasibility, clinical improvement, and morbidity. METHODS: Twenty-five consecutive patients with diagnosis of MESCC from solid primary tumors were treated between January 2008 and June 2010 at our institution. All patients, after multidisciplinary assessment, were considered with poor prognosis because of their disease's extension and/or other clinical conditions. Mini-invasive percutaneous surgery was performed in all patients followed by radiotherapy within 2 weeks postoperatively. Clinical outcome was evaluated by modified visual analog scale for pain, Frankel Scale for neurologic deficit, and magnetic resonance imaging or computed tomography scan. RESULTS: Clinical remission of pain was obtained in the vast majority of patients (96%). Improvement of neurological deficit was observed in 22 patients (88%). No major morbidity or perioperative mortality occurred. The average hospital stay was 6 days. Local recurrence occurred in two patients (8%). Median survival was 10 (range, 6-24) months. Overall survival at 1 year was 43%. CONCLUSIONS: For patients with MESCC and body fracture, with limited life expectancy, minimally invasive spinal surgery followed by radiotherapy, is feasible and provides clinical benefit in most of patients, with low morbidity. We believe that a minimally invasive approach can be an alternative surgical method compared with more aggressive or demanding procedures, which in selected patients with metastatic spinal cord compression with poor prognosis could represent overtreatment.

Vertebral metastases reirradiation with volumetric-modulated arc radiotherapy.

PURPOSE: To assess the feasibility, acute toxicity, clinical improvement, local control and survival for spinal metastatic patients re-irradiated using volumetric-modulated-arc-radiotherapy (VMAT). METHODS AND MATERIALS: Between February 2009 and November 2010, 31 patients were treated. Surgery was performed in six before re-irradiation. The clinical target volume (CTV) was defined as the whole vertebrae with recurrence excluding the central section of spinal canal. Planning target volume was defined as CTV+0-5mm in the three directions. Dose was prescribed in order to have biological equivalent dose to the spinal cord from the two courses lower than 120 Gy(2) to 1 cc of the volume. Clinical improvement, toxicity and recurrence were evaluated. All patients had back pain before treatment and 15 (48%) neurological deficit. RESULTS: Clinical remission of pain was obtained in 29 patients (93%). Neurological improvement was observed in 73% of patients. No acute or late toxicities were recorded. No recurrence occurred. Median survival was 10 months (range 6-24). At the last follow-up 19 patients (61%) were alive and 12 (39%) dead from systemic disease progression. The 1 and 2 year survival were 55% and 35%, respectively. CONCLUSION: In patients with spinal metastases recurrence re-irradiation with VMAT is feasible and provides clinical benefit in most patients.

Percutaneous vertebral augmentation in metastatic disease: state of the art.

Improvements in diagnosis and treatment have prolonged cancer survival, with a consequent increase in the incidence of spinal metastases and vertebral compression fractures with associated axial pain, progressive radiculomyelopathy, and mechanical instability. Pain relief in malignant vertebral compression fractures is key to achieving a better quality of life in patients under palliative care. The gold standard for pain relief is nonsteroidal anti-inflammatory drugs and opioids. Nonresponsive cases are then treated with radiotherapy, which may require 2-4 weeks to take effect and in most cases does not provide complete pain relief. Percutaneous vertebroplasty and percutaneous kyphoplasty can in particular give relief in patients with vertebral body compression fractures that do not cause neurological deficits but severely compromise quality of life because of intractable pain.

Surgery followed by radiotherapy for the treatment of metastatic epidural spinal cord compression from breast cancer.

STUDY DESIGN: Retrospective analysis of breast cancer patients with metastatic epidural spinal cord compression (MESCC) undergoing surgery and radiation therapy. OBJECTIVE: To assess feasibility and clinical outcome of multidisciplinary approach in breast cancer patients with MESCC. SUMMARY OF BACKGROUND DATA: Studies so far published in the setting of surgery and/or radiotherapy in the management of MESCC usually included many malignancies, without considering the different primary histology. However, when looking at prognostic variables of this therapy, histological type comes out as a major determinant of outcome. METHODS: Twenty-three patients with symptomatic MESCC from breast cancer treated between January 2004 and April 2009 were included in this analysis. Twenty-six surgical procedures followed by radiotherapy were performed. Clinical outcome and local recurrence was evaluated by modified visual analog scale for pain, Frankel scale for neurologic deficit, and magnetic resonance imaging or computed tomography scans. Twenty-three cases (88.4%) had back pain before treatment with a visual analog scale score 6 or greater; neurologic deficit (FS A-D) was present in 19 cases (65.5%). RESULTS: Complete remission of pain, lasting until death or progression of disease in another skeletal site, was obtained in 25/26 cases (96.1%). All patients had complete recovery of neurologic deficit. No major morbidity occurred. No patients had recurrence in the site of treatment. Median survival was 36 months (range, 3-60) and overall survival at one, three, and five years was 70%, 42%, and 34%, respectively. CONCLUSION: We provided evidence of surgery and radiotherapy to be feasible with limited morbidity. Clinical outcome has been highly satisfactory in terms of pain and local disease control. The discussion of each case within a multidisciplinary team is of central importance in defining the most appropriate therapeutic approach.

Multimodal approach to the management of metastatic epidural spinal cord compression (MESCC) due to solid tumors.

PURPOSE: To assess the impact of a multidisciplinary approach for treatment of patients with metastatic epidural spinal cord compression in terms of feasibility, local control, and survival. METHODS AND MATERIALS: Eighty-nine consecutive patients treated between January 2004 and December 2007 were included. The most common primary cancers were lung, breast, and kidney cancers. Ninety-eight surgical procedures were performed. Radiotherapy was performed within the first month postoperatively. Clinical outcome was evaluated by modified visual analog scale for pain, Frankel scale for neurologic deficit, and magnetic resonance imaging or computed tomography scan. Nearly all patients (93%) had back pain before treatment, whereas major or minor preoperative neurologic deficit was present in 62 cases (63%). RESULTS: Clinical remission of pain was obtained in the vast majority of patients (91%). Improvement of neurologic deficit was observed in 45 cases (72.5%). Local relapse occurred in 10%. Median survival was 11 months (range, 0-46 months). Overall survival at 1 year was 43.6%. Type of primary tumor significantly affected survival. CONCLUSIONS: In patients with metastatic epidural spinal cord compression, the combination of surgery plus radiotherapy is feasible and provides clinical benefit in most patients. The discussion of each single case within a multidisciplinary team has been of pivotal importance in implementing the most appropriate therapeutic approach.

Vertebroplasty for pain relief and spinal stabilization in multiple myeloma.

Mechanical stabilization of oncological vertebral fractures with cement augmentation is the first mechanism of pain relief, with or without restoration of vertebral body height. The aim of this study was to assess the safety and efficacy of vertebroplasty for painful vertebral body fractures in patients with multiple myeloma, in each phase of the disease. The authors reviewed a consecutive group of patients with multiple myeloma who underwent vertebroplasty at our Institute between November 2003 and December 2005. Twenty-eight levels were performed on 11 patients during 14 treatment sessions. All patients suffered from intractable back pain, and presented various lesion types (with and without fractures of posterior wall, and with and without epidural disease). The preoperative median visual analog scale (VAS) score was 7. The median duration of symptoms was 1.1 months. Eight patients were ambulating with orthopaedic devices (57%) in the pre-treatment period. Improvement or complete pain relief was observed in all patients (immediately in 8 cases, and after 2 days in 6 cases). The median VAS pain score decreased to 2. There was no symptomatic procedure-related complication. There were three cases (21%) of PMMA leakage: in the disc space in one case (7%), and in the anterior spinal canal in two cases (14%). Complete removal of orthopaedic devices was obtained in five patients (36%). No new deformation or collapse of the treated vertebrae was observed during the follow-up (range 1 day-25 months). In conclusion, vertebroplasty is a safe and efficient procedure in the treatment of painful vertebral body fractures in patients with multiple myeloma, without potential contraindications, such as fractures of the posterior wall or epidural disease. We also treated three and more levels in 28% of cases in a single session without complications. Due to the early pain relief and the low complication rate, it is possible to expand the indication to vertebroplasty for the prophylactic augmentation of those vertebral bodies at risk of fracture in which significant neoplastic substitution of the body is present.

High incidence of hypocalcemia and serum creatinine increase in patients with bone metastases treated with zoledronic acid.

BACKGROUND: Zoledronic acid belongs to the new generation of bisphosphonates with demonstrated clinical benefit for the treatment of bone metastases from different kinds of neoplasms. Hypocalcemia and serum creatinine elevation are expected adverse events during this therapy. The monitoring of serum calcium and creatinine is therefore recommended. The primary aim of this study was to establish the actual incidence of hypocalcemia and serum creatinine elevation during treatment with zoledronic acid. Skeletal-related events and side effects were also assessed. METHODS: Serum creatinine and calcium levels were evaluated in 240 consecutive patients (83 males, 157 females; mean age, 62 years) with metastatic bone lesions from different solid tumors treated with zoledronic acid. RESULTS: Overall, 93 of 240 patients (38.8%) developed hypocalcemia, which was grade (G)1 in 45 patients (48.4%), G2 in 37 patients (39.8%), G3 in 10 patients (10.8%), and G4 in one patient (1.1%). The median time to occurrence of hypocalcemia (any grade) was 2.3 months after the beginning of the treatment (range, 0-34.9 months). Increased serum creatinine was observed in 33 of 240 patients (13.7%), of whom 19 had G1 (57.6%), 11 had G2 (33.3%), and three had G3 (9.1%). The median time to serum creatinine increase (for any grade) was 4.7 months (range, 0-29.2 months). CONCLUSIONS: Our analysis shows a high incidence of hypocalcemia and increased serum creatinine level during treatment with zoledronic acid. These results strongly support the need for accurate monitoring of plasma calcium and creatinine levels.

Adipose-derived stem cell therapy for intervertebral disc regeneration: an in vitro reconstructed tissue in alginate capsules.

The degenerative pathologies of the intervertebral disc have a remarkable social impact in the industrialized countries and can provide serious disabilities in the population. The current treatment consists of conservative treatments (such as symptomatic pharmacological therapies and physiokinetic therapy) and surgical treatments (intervertebral fusion, total disc replacement, nucleus pulposus (NP) replacement, or surgical exeresis). Recent advances in cell therapy foresee the possibility of regenerating the damaged disc; the autologous disc tissue can be withdrawn, in vitro regenerated, and re-implanted. The aim of this work was to verify whether autologous adipose-derived adult stem cells can improve the quality of an in vitro reconstructed nucleus pulposus tissue. A three-dimensional (3D) co-culture of NP cells and adipose tissue non-adipocyte fraction cells (nAFs) was assessed in a previously developed alginate 3D culture system following the good manufacturing practice guidelines to ensure patient safety for clinical studies. Morphological investigation of cultured and co-cultured cells was performed using transmission electron microscopy and immunofluorescence for collagen type I, aggrecan, CD90, CD34, and vimentin. Results indicate that co-culture of NP and nAFs improves the quality of the in vitro reconstructed tissue in term of extracellular matrix production and 3D cell organization. Technological resources are available for NP cell encapsulation intended for regenerating the intervertebral disc.

The neuroanatomical plates of Guido da Vigevano.

Guido da Vigevano was an Italian physician and engineer who lived in the 13th and 14th centuries. He was the first scientist who used pictures to illustrate his anatomical descriptions, developing for the first time a close relationship between anatomical studies and artistic drawings. This was further developed in the Renaissance. In his textbook Anathomia are displayed six plates showing for the first time neuroanatomical structures and techniques: dissection of the head by means of trephination, and depictions of the meninges, cerebrum, and spinal cord. On the surface of the brain painting it is possible to recognize a vague patterning of cortical convolutions. Ventricles are also described and shown. This book constituted the first attempt in the history of neuroscience to illustrate an anatomical description with schematic pictures to achieve a better understanding of such complex structures.

Fractal dimension as a quantitator of the microvasculature of normal and adenomatous pituitary tissue.

It is well known that angiogenesis is a complex process that accompanies neoplastic growth, but pituitary tumours are less vascularized than normal pituitary glands. Several analytical methods aimed at quantifying the vascular system in two-dimensional histological sections have been proposed, with very discordant results. In this study we investigated the non-Euclidean geometrical complexity of the two-dimensional microvasculature of normal pituitary glands and pituitary adenomas by quantifying the surface fractal dimension that measures its space-filling property. We found a statistical significant difference between the mean vascular surface fractal dimension estimated in normal versus adenomatous tissues (P = 0.01), normal versus secreting adenomatous tissues (P = 0.0003), and normal versus non-secreting adenomatous tissues (P = 0.047), whereas the difference between the secreting and non-secreting adenomatous tissues was not statistically significant. This study provides the first demonstration that fractal dimension is an objective and valid quantitator of the two-dimensional geometrical complexity of the pituitary gland microvascular network in physiological and pathological states. Further studies are needed to compare the vascular surface fractal dimension estimates in different subtypes of pituitary tumours and correlate them with clinical parameters in order to evaluate whether the distribution pattern of vascular growth is related to a particular state of the pituitary gland.

Spinal decompression and vertebroplasty in Paget's disease of the spine.

Paget's disease is an osteometabolic disorder affecting in particular long bones. The spine is the second most commonly involved site in Paget's disease. This pathology can cause low back pain, spinal stenosis, myeloradiculopathy, and vertebral collapse. Medical therapy is the first choice for the treatment of Paget's disease of the spine; in case of failure, surgery remains a valid option. In the present article, we report a case of a patient with leg disability due to myelopathy caused by spinal Paget's disease treated with spinal decompression and vertebroplasty. To our knowledge, this is the first case report in which these procedures have been performed together in the same operation to treat spinal pathologies due to Paget's disease.

Functional disability after instrumented stabilization in lumbar degenerative spondylolisthesis: a follow-up study.

Low back pain (LBP) is a widespread health problem and a major contributor to increasing health costs and lost work days. Different pathologies cause LBP and one of these is lumbar degenerative spondylolisthesis (SPL). There are no generally accepted and standardized methods for assessing the outcome of patients treated for degenerative lumbar SPL. This study aims to assess quality of life after surgery for lumbar degenerative SPL through the adoption of outcome measures. We studied 76 patients treated, for degenerative lumbar SPL, with spinal stabilization, decompression and bilateral dorsolateral fusion, followed up for at least two years. We used the Roland-Morris (RM) scale and the Oswestry Disability Index (ODI) to assess the quality of life of the patients before surgery and at follow up. Each patient was pre-operatively studied through standard and dynamic x-rays, CT scan and MRI of lumbar column. Relationships between clinical, radiological and disability scores, grouped by categories, were tested. The sample comprised 25 males and 51 females. Mean age was 59.6 years (SD 12.2). The mean duration of symptoms (from clinical onset to surgery) was 23.42 months (median 13, range 4-100 months). In about half of the cases, duration of symptoms before surgery was >12 months. At follow up, the fusion rate was 85.5%, and the ODI score was significantly reduced: an improvement of <20 points in 35.7% of patients, and of >20 points in 55.7%. On the RM scale, 59.4% of patients had a reduction >5 points, 13.1% a reduction of 2-4 points, and 27.5% an unchanged or worse score. There was no significant reduction in RM scale and ODI scores in patients with fusion versus pseudoarthrosis. Instrumental pedicle screw fixation and arthorodesis seem to be very effective in improving quality of life, as shown by the reduced disability scores at follow up.

Calvarial metastases as clinical presentation of renal cell carcinoma: report of two cases and review of the literature.

Calvarium is a frequent target site of involvement for common neoplasms. Some cases of calvarial metastases have been reported in literature as secondary lesions from renal cell carcinoma (RCC), but only five cases have been described concerning calvarial mass as the first clinical presentation of this kind of tumor. In this report, we discuss the clinical aspects of two further cases we observed, in which the renal cell carcinoma was found thanks to the histological examination of a calvarial mass after surgery. We also briefly review the literature.

Surgery for herniated lumbar disc disease: factors influencing outcome measures. An analysis of 403 cases.

The records of 403 patients treated for herniated lumbar disc disease were analysed in a retrospective observational study in order to verify how three outcome measures, i.e., satisfaction with the outcome of surgery, the degree of return to activities of daily living including work (ADL), and duration of interruption of ADL, may be influenced by clinical variables. Age, type of disc herniation, radiological evidence of recurrence (radiological recurrence), and need for a second surgical operation for disc herniation (surgical recurrence) were found to be significantly related to the patient's satisfaction with the outcome of surgery at follow up. Satisfaction with the outcome of surgery was not found to depend on the interval between clinical onset and radiological diagnosis, or on the timing of surgery. The degree of return to ADL was found to be significantly related to age, surgical recurrence, type of disc herniation, and timing of surgery. The results of the present study suggest that age and type of disc herniation are among the most important factors to consider when deciding whether or not to operate on a patient for herniated lumbar disc and that return to ADL after surgery is closely correlated with disc disease recurrence.

Diagnostic potential of autofluorescence for an assisted intraoperative delineation of glioblastoma resection margins.

The intrinsic autofluorescence properties of biological tissues can be affected by the occurrence of histological and biochemical alterations induced by pathological processes. In this study the potential of autofluorescence to distinguish tumor from normal tissues was investigated with the view of a real-time diagnostic application in neurosurgery to delineate glioblastoma resection margins. The autofluorescence properties of nonneoplastic and neoplastic tissues were analyzed on tissue sections and homogenates by means of a microspectrofluorometer, and directly on patients affected by glioblastoma multiforme, during surgery, with a fiber-optic probe. Scan-microspectrofluorometric analysis on tissue sections evidenced a reduction of emission intensity and a broadening of the main emission band, along with a redshift of the peak position, from peritumoral nonneoplastic to neoplastic tissues. Differences in both spectral shape and signal amplitude were found in patients when the glioblastoma lesion autofluorescence was compared with those of cortex and white matter taken as healthy tissues. Both biochemical composition and histological organization contribute to modify the autofluorescence emission of neoplastic, with respect to nonneoplastic, brain tissues. The differences found in the in vivo analysis confirm the prospects for improving the efficacy of tumor resection margin delineation in neurosurgery.