Nicolas R. Smoll

Variations of the piriformis and sciatic nerve with clinical consequence: a review.

The deep gluteal region is often encountered when performing injections, when performing surgery such as total hip replacements, or diagnosing problems of this region or lower limbs using clinical or imaging techniques. Previously, the prevalence figures of piriformis and sciatic nerve anomalies have ranged from 1.5 to 35.8% in dissected specimens. This study systematically reviews and meta‐analyses the prevalence of piriformis and sciatic nerve anomalies in humans using previously published literature. A further review is conducted regarding the anatomical abnormalities present in surgical case series of procedures for patients suffering from piriformis syndrome. After pooling the results of 18 studies and 6,062 cadavers, the prevalence of the anomaly in cadavers was 16.9%; 95% confidence interval (CI) 16.0–17.9%. The prevalence of the piriformis and sciatic nerve anomaly in the surgical case series was 16.2%, 95% CI: 10.7–23.5%. The difference between the two groups was not found to be significant 0.74%; 95% CI: −5.66 to 7.13; P = 0.824. Because of the high likelihood of an anomaly being present in a patient, clinicians and surgeons should be aware of the potential complications this anomaly may have on medical or surgical interventions. Furthermore, because the prevalence of the anomaly in piriformis syndrome patients is not significantly different from what is thought to be a normal population, it indicates that this anomaly may not be as important in the pathogenesis of piriformis syndrome as previously thought. Clin. Anat. 23:8–17, 2010.

The incidence of medulloblastomas and primitive neurectodermal tumours in adults and children

Medulloblastomas (MB) and primitive neurectodermal tumours (PNET) are known to affect children more than adults. To estimate the magnitude of the differences between the incidence of adults and children, the incidence rates, ratios and time trends of MB and PNET in children and adults are measured using data from the Surveillance, Epidemiology and End-Results (SEER) database. Between 1973 and 2007 in the SEER 9 registries, 1372 people were diagnosed with a MB and 530 with a PNET. The overall incidence rate of MB and PNET is approximately 1.5 and 0.62 per million population in the USA. Children (1-9 years of age) with MB had an incidence rate of 6.0, compared to 0.6 in adults, and therefore children are 10 times more likely to be affected by an MB than adults. Children are 4.6 times as likely to be afflicted by a PNET than adults. The difference in incidence rates based on sex existed only in children. Our study confirmed that the incidence rates of MB has not changed over time.

Relative survival of childhood and adult medulloblastomas and primitive neuroectodermal tumors (PNETs)

Medulloblastomas are 1 of the most common brain tumors in children but can affect individuals of all ages. For this report, the author investigated the impact of medulloblastomas/primitive neuroectodermal tumors (PNETs) on the US population with a focus on age differences.

Long-term survival of patients with glioblastoma multiforme (GBM)

Long-term survival is an often used, yet poorly defined, concept in the study of glioblastoma multiforme (GBM). This study suggests a method to define a time-point for long-term survival in patients with GBM. Data for this study were obtained from the Surveillance, Epidemiology and End-Results database, which was limited to the most recent data using the period approach. Relative survival measures were used and modelled using piecewise constant hazards to describe the survival profile of long-term survivors of GBM. For patients with GBM, the first quarter of the second year (5th quarter) post-diagnosis is considered to be the peak incidence of mortality with an excess hazard ratio of 7.58 (95% confidence interval=6.54, 8.78) and the risk of death due to GBM decreases to half of its rate at 2.5 years post-diagnosis. The 2.5-year cumulative relative survival (CRS) for all patients is approximately 8%, with a CRS of approximately 2% at 10 years. Using the definition of long-term survival suggested here, the results indicate that long-term survivors are patients who survive at least 2.5 years post-diagnosis. The most likely time period for patients with GBM to die is the 5th quarter post-diagnosis.

Relative survival of patients with supratentorial low-grade gliomas

We sought to assess the population-based estimates of age-standardized survival among patients with low-grade gliomas (LGG) and to determine the impact of age and time on relative survival (RS). Data from the Surveillance, Epidemiology, and End Results (SEER) program of NCI from 1973 through 2006 were analyzed to assess survival among 5037 patients. Relationships were modeled using Dickmans piecewise constant hazards RS model. The 3- and 10-year age-standardized RS were 67% and 37%, respectively. When analyzed by age group, the 10-year overall survival (OS) and RS for children (age, <16 years), young adults (age, 16-39 years), adults (age, 40-64 years), and older patients (age, ≥65 years) were 86% and 86%, 61% and 62%, 40% and 43%, and 10% and 14%, respectively. The observed difference between OS and RS was larger among older patients (4%) and smallest among children (<1%). Older patients were 30.5 times (excess hazard ratio [eHR]; 95% confidence interval [CI], 20.3-50.0) as likely as young adults to die during the first year and 18.2 times as likely to die during the second year. Adults were 5.3 (eHR; 95% CI, 3.5-8.1) times as likely to die during their first year as young adults. In the remaining years, the observed survival differences were substantially decreased, and the presence of an age-by-follow-up interaction was observed. Survival among older patients with LGG was substantially different from the one computed for young adults and children. Despite the hazards across age groups not being proportional, RS does not provide additional information, compared with OS, in patients with LGG.

The need for an objective outcome measurement in spine surgery—the timed-up-and-go test

The primary goal of spine surgery is to alleviate pain, improve function, and maximize health-related quality of life. Thus, the accurate measurement of pain, function, and health-related quality of life in a clinical setting is of paramount importance. Currently, there are valid, reliable, and useful subjective measures of pain and function, notably the visual analogue scale and Oswestry or RolandMorris scale. These are questionnaires typically given to a patient for self-dependent rating. Despite extensive validation and testing as well as frequent application of these scales in clinical practice today, they carry weaknesses inherent to their subjective nature. One of the major limitations of subjective outcome measurement tools is a restricted comparability. Patients rate their subjective pain or functional disability differently; reasons for this include educational, cultural, and motivational varieties. In addition, each outcome scale can be misinterpreted, thus leading to interrater and intrarater reliability issues. The clear benefits of these scales are that they measure the patient’s own (subjective) perception of his/her current disability related to pain and functional restraint. Although Deyo et al. [1] recommended the introduction of uniform standards for measuring patientreported outcomes more than 15 years ago, there is still no international consensus regarding outcome assessment in spine surgery. Existing objective outcome measures in spine surgery include measurement of range of movement (eg, with a goniometer), measurement of muscle strength (eg, with a newton metre), or measurement of walking speed and walking distance, besides radiographic findings. More recently, complex objective outcome measures have been tested using advanced tracking technology based on Global Positioning Systems [2]. Despite considerable efforts, none of these objective measurements has been generally implemented into daily clinical routine. In daily clinical practice, the decision to operate is generally drawn from a review of the patient’s history, neurologic examination, and functional status. To establish a standardized, comprehensive, and complete outcome assessment in spine surgery, objective measures of function, for example, the ‘‘timed-up-and-go test’’ (TUG), should be validated and introduceddin addition to the already established subjective outcome measurements. The TUG test originated as an object measure of function in the elderly population to predict falls as walking speed has been identified as a predictor of falls and even overall survival [3]. The TUG test is quick to perform and requires equipment that can be found at the patient’s bedside (chair and 3 m of walking space). Overall, the TUG test reproduces simple but nonetheless important functions performed by virtually all ambulant humans on a daily basis: stand-up, walk, change direction, walk again, and sit down. These are functions that are essential for patients after spine surgery to maintain activities of daily living and quality of life. For the field of lumbar spine surgery, the TUG test seems to be a good candidate for an objective measurement of function because of several desirable qualities: It is quick (certainly much quicker than subjective outcome measures), has high interrater reliability/low interrater variability (seen in other studies), and is easily interpretable with no scoring required and well appreciated by patients.

Podocalyxin-Like Protein Is Expressed in Glioblastoma Multiforme Stem-Like Cells and Is Associated with Poor Outcome

Glioblastoma multiforme (GBM) is the most common primary malignant adult brain tumor and is associated with poor survival. Recently, stem-like cell populations have been identified in numerous malignancies including GBM. To identify genes whose expression is changed with differentiation, we compared transcript profiles from a GBM oncosphere line before and after differentiation. Bioinformatic analysis of the gene expression profiles identified podocalyxin-like protein (PODXL), a protein highly expressed in human embryonic stem cells, as a potential marker of undifferentiated GBM stem-like cells. The loss of PODXL expression upon differentiation of GBM stem-like cell lines was confirmed by quantitative real-time PCR and flow cytometry. Analytical flow cytometry of numerous GBM oncosphere lines demonstrated PODXL expression in all lines examined. Knockdown studies and flow cytometric cell sorting experiments demonstrated that PODXL is involved in GBM stem-like cell proliferation and oncosphere formation. Compared to PODXL-negative cells, PODXL-positive cells had increased expression of the progenitor/stem cell markers Musashi1, SOX2, and BMI1. Finally, PODXL expression directly correlated with increasing glioma grade and was a marker for poor outcome in patients with GBM. In summary, we have demonstrated that PODXL is expressed in GBM stem-like cells and is involved in cell proliferation and oncosphere formation. Moreover, high PODXL expression correlates with increasing glioma grade and decreased overall survival in patients with GBM.

Outcomes after combined use of intraoperative MRI and 5-aminolevulinic acid in high-grade glioma surgery

Background Previous studies have shown the individual benefits of 5-aminolevulinic acid (5-ALA) and intraoperative (i)MRI in enhancing survival for patients with high-grade glioma. In this retrospective study, we compare rates of progression-free and overall survival between patients who underwent surgical resection with the combination of 5-ALA and iMRI and a control group without iMRI. Methods In 200 consecutive patients with high-grade gliomas, we recorded age, sex, World Health Organization tumor grade, and pre- and postoperative Karnofsky performance status (good ≥80 and poor <80). A 0.15-Tesla magnet was used for iMRI; all patients operated on with iMRI received 5-ALA. Overall and progression-free survival rates were compared using multivariable regression analysis. Results Median overall survival was 13.8 months in the non-iMRI group and 17.9 months in the iMRI group (P = .043). However, on identifying confounding variables (ie, KPS and resection status) in this univariate analysis, we then adjusted for these confounders in multivariate analysis and eliminated this distinction in overall survival (hazard ratio: 1.23, P = .34, 95% CI: 0.81, 1.86). Although 5-ALA enhanced the achievement of gross total resection (odds ratio: 3.19, P = .01, 95% CI: 1.28, 7.93), it offered no effect on overall or progression-free survival when adjusted for resection status. Conclusions Gross total resection is the key surgical variable that influences progression and survival in patients with high-grade glioma and more likely when surgical adjuncts, such as iMRI in combination with 5-ALA, are used to enhance resection.

Sex differences in subjective and objective measures of pain, functional impairment, and health-related quality of life in patients with lumbar degenerative disc disease.

Abstract Sex differences in pain perception are known to exist; however, the exact pathomechanism remains unclear. This work aims to elucidate sex differences in subjective and objective measures of pain, functional impairment, and health-related quality of life (HRQoL) in patients with lumbar degenerative disc disease. In a prospective 2-center study, back and leg pain (visual analogue scale [VAS]), functional disability (Oswestry Disability Index and Roland–Morris Disability Index), and HRQoL (EuroQol-5D and Short Form [SF12]) were collected for consecutive patients undergoing lumbar spine surgery. Objective functional impairment (OFI) was estimated using age-adjusted and sex-adjusted cutoff values for the timed-up-and-go (TUG) test. A healthy cohort of n = 110 subjects served as the control group. Univariate and multivariate analyses were performed to test the association between sex and pain, subjective and OFIs, and HRQoL. The study comprised n = 305 patients (41.6% females). Female patients had more VAS back pain (P = 0.002) and leg pain (P = 0.014). They were more likely to report higher functional impairment in terms of Oswestry Disability Index (P = 0.005). Similarly, HRQoL measured with the EuroQol-5D index (P = 0.012) and SF12 physical composite score (P = 0.005) was lower in female patients. Female patients reported higher VAS back and leg pain, functional impairment, and reduced HRQoL than male patients. However, there were no sex differences with respect to the presence and degree of OFI measured by the TUG test using age-adjusted and sex-adjusted cutoff values. As such, the TUG may be a good test to overcome sex bias for the clinical assessment of patients with degenerative disc disease.

Clinically relevant complications related to posterior atlanto-axial fixation in atlanto-axial instability and their management

BACKGROUND The Magerl transarticular technique and the Harms-Goel C1 lateral mass-C2 isthmic screw technique are the two most commonly used surgical procedures to achieve fusion at C1-C2 level for atlanto-axial instability. Despite recent technological advances with an increased safety, several complications may still occur, including vascular lesions, neurological injuries, pain at the harvested bone graft site, infections, and metallic device failure. METHODS We retrospectively analyzed all patients (n=42 cases) undergoing a Harms-Goel C1-C2 fixation surgery with polyaxial C1 lateral mass screws and C2 isthmic screws at two different institutions between 2003 and 2012 and report clinical and radiological complications. One patient was lost to follow-up. The mean follow-up of the remaining 41 patients was 18.7 months (range 12-90). A clinically relevant complication was defined as a complication determining the onset of a new neurological deficit or requiring the need for a revision surgery. RESULTS A total of 14 complications occurred in 10 patients (24.4% of 41 patients). Greater occipital nerve neuralgia was evident in 4 patients (9.8%). All but one completely resolved at the end of the follow-up. Persistent neck pain was reported by 3 patients (7.3%), hypoesthesia by 1 patient (2.4%), and anesthesia in the C2 area on both sides in 1 patient (2.4%). Furthermore, a superficial, a deep, and a combined superficial and deep wound infection occurred in 1 patient each (2.4%). One patient (2.4%) had pain at the iliac bone graft donor site for several weeks with spontaneous resolution. A posterior progressive intestinal herniation through the iliac scar was seen in 1 case (2.4%), which required surgical repair. No vascular damages occurred. Altogether, 5/41 patients (12.2%) had a clinically relevant complication including 4 patients necessitating a revision surgery at the C1-C2 level (9.8%). CONCLUSIONS Atlanto-axial fixation surgery remains a challenging procedure because of the proximity of important neurovascular structures. Nevertheless, on the basis of our current experience, the C1 lateral mass-C2 isthmic screw technique appears to be safe with a low incidence of clinically relevant complications. Postoperative C2 neuralgia, as the most frequent problem, is due to surgical manipulation during preparation of the C1 screw entry point.