Neurosurgical FOCUS

Published by American Association of Neurological Surgeons
Adjuvant nitrosourea chemotherapy fails to prolong patient survival significantly as many tumors demonstrate resistance to these drugs. It has been documented in cell lines that O ⁶ -methylguanine-DNA methyltransferase (MGMT) plays an important role in chloroethylnitrosourea (CENU) drug resistance. The authors evaluated MGMT expression in 22 glioma specimens by using an immunofluorescence assay and compared the results with clinical response of the patients to CENU-based chemotherapy. The patients were treated with CENU after evidence of progressive disease following surgery and radiotherapy. Eight tumor samples had no detectable MGMT, whereas other samples had from 9989 to 982,401 molecules/nucleus. In one group (12 patients), the tumor decreased in size or was stable (effective group), whereas in the other group (10 patients), the tumor demonstrated continuous growth during chemotherapy (progressive group). The median time to progression (TTP) was 6.7 months with a median survival of 13 months. The Mer ⁻ patients (MGMT < 60,000 molecules/nucleus) appeared to have more chance of stable disease or response to CENU therapy than the Mer ⁺ patients (MGMT > 60,000 molecules/nucleus) (chi-square = 4.791, p = 0.0286). In patients with glioblastomas multiforme (GBMs), the TTP of Mer ⁺ patients was shorter than that of Mer ⁻ patients (t = 2.04, p = 0.049). As a corollary, the MGMT levels were significantly higher in GBM tumors from the progressive group than those from the effective group (t = -2.26, p = 0.029). The TTP and survival time in the effective GBM group were also longer than those in the progressive GBM group. However, there was no significant correlation between MGMT levels and either the survival time (r = 0.04, p = 0.8595) or TTP (r = 0.107, p = 0.6444). Results from this study suggested that MGMT positivity is indicative of more aggressive disease that progresses more rapidly when exposed to CENU therapy. However, MGMT-negative tumors are not always sensitive to CENU agents, suggesting that other factors may also be important.
Object: The objective of this study was to report the authors' experience with the long-term administration of temozolomide (TMZ; > 6 cycles, up to 101) in patients with newly diagnosed glioblastoma and to analyze its feasibility and safety as well as its impact on survival. The authors also compared data obtained from the group of patients undergoing long-term TMZ treatment with data from patients treated with a standard TMZ protocol. Methods: A retrospective analysis was conducted of 37 patients who underwent operations for glioblastoma between 2004 and 2012. Volumetric analysis of postoperative Gd-enhanced MR images, obtained within 48 hours, confirmed tumor gross-total resection (GTR) in all but 2 patients. All patients received the first cycle of TMZ at a dosage of 150 mg/m(2) starting on the second or third postsurgical day. Afterward, patients received concomitant radiochemotherapy according to the Stupp protocol. With regard to adjuvant TMZ therapy, the 19 patients in Group A, aged 30-72 years (mean 56.1 years), received 150 mg/m(2) for 5 days every 28 days for more than 6 cycles (range 7-101 cycles). The 18 patients in Group B, aged 46-82 years (mean 64.8 years), received the same dose, but for no more than 6 cycles. O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was analyzed for both groups and correlated with overall survival (OS) and progression-free survival (PFS). The impact of age, sex, Karnofsky Performance Scale score, and Ki 67 staining were also considered. Results: All patients but 1 in Group A survived at least 18 months (range 18-101 months), and patients in Group B survived no more than 17 months (range 2-17 months). The long-term survivors (Group A), defined as patients who survived at least 12 months after diagnosis, were 51.3% of the total (19/37). Kaplan-Meier curve analysis showed that patients treated with more than 6 TMZ cycles had OS and PFS that was significantly longer than patients receiving standard treatment (median OS 28 months vs 8 months, respectively; p = 0.0001; median PFS 20 months vs 4 months, respectively; p = 0.0002). By univariate and multivariate Cox proportional hazard regression analysis, MGMT methylation status and number of TMZ cycles appeared to be survival prognostic factors in patients with glioblastoma. After controlling for MGMT status, highly significant differences related to OS and PFS between patients with standard and long-term TMZ treatment were still detected. Furthermore, in Group A and B, the statistical correlation of MGMT status to the number of TMZ cycles showed a significant difference only in Group A patients, suggesting that MGMT promoter methylation was predictive of response for long-term TMZ treatment. Prolonged therapy did not confer hematological toxicity or opportunistic infections in either patient group. Conclusions: This study describes the longest experience so far reported with TMZ in patients with newly diagnosed glioblastomas, with as many as 101 cycles, who were treated using GTR. Statistically significant data confirm that median survival correlates with MGMT promoter methylation status as well as with the number of TMZ cycles administered. Long-term TMZ therapy appears feasible and safe.
Object: There has been a tremendous increase in the incidence of deformational plagiocephaly in children throughout the world. Therapeutic options include observation, active counterpositioning, external orthotics, and surgery. The current treatment in the US is highly debated, but it typically includes external orthotic helmets in patients with moderate to severe plagiocephaly presenting between 4 and 10 months of age or in children with significant comorbidities limiting passive (no-pressure) therapy. The present study was designed to evaluate 3 key issues: 1) the accuracy of the Argenta classification in defining a progressive degree of severity, 2) identification of an upper age limit when treatment is no longer effective, and 3) the effectiveness of an off-the-shelf prefabricated helmet in correcting deformational plagiocephaly. Methods: An institutional review board-approved retrospective study was conducted of all patients at the authors' clinic in whom deformational plagiocephaly was assessed using the Argenta classification system over a 6-year period; the patients underwent helmet therapy, and a minimum of 3 clinic visits were recorded. Inclusion criteria consisted of an Argenta Type II-V plagiocephalic deformity. Patients' conditions were categorized both by severity of the deformity and by patients' age at presentation. Statistical analysis was conducted using survival analysis. Results: There were 1050 patients included in the study. Patients with Type III, IV, and V plagiocephaly required progressively longer for deformity correction to be achieved than patients with Type II plagiocephaly (53%, 75%, and 81% longer, respectively [p < 0.0001]). This finding verified that the Argenta stratification indicated a progressive severity of deformity. No statistically significant difference in the time to correction was noted among the different age categories, which suggests that the previously held upper time limit for correction may be inaccurate. An overall correction rate to Type I plagiocephaly of 81.6% was achieved irrespective of severity and degree of the original deformity. This suggests that an inexpensive off-the-shelf molding helmet is highly effective and that expensive custom-fitted orthoses may not be necessary. The patients in the older age group (> 12 months) did not have a statistically significant longer interval to correction than the patients in the youngest age group (< 3 months). The mean length of follow-up was 6.3 months. Conclusions: Patients treated with passive helmet therapy in the older age group (> 12 months) had an improvement in skull shape within the same treatment interval as the patients in the younger age group (< 3 months). This study supports the use of passive helmet therapy for improvement in deformational plagiocephaly in infants from birth to 18 months of age and verifies the stratification of degree of deformity used in the Argenta classification system.
This study was designed to determine the surgical technique and surgery-related outcome, fusion rate, and complication of anterior decompression and fusion (with various graft materials) performed in patients with ossification of the posterior longitudinal ligament (OPLL) of the cervical spine. Between 1980 and 1998, 107 patients with radiologically proven OPLL underwent surgery via the anterior approach for direct removal of the ossified mass. Graft materials included iliac crest in 45 cases, vertebral body (VB) in 37 cases; and interbody fusion cages in 25 cases. In four patients with three-level VB grafts and one with a two-level VB graft, anterior plates were placed. Surgery-related outcome was excellent or good in 89% and fair in 11%. This clinical improvement correlated well with the severity of preoperative myelopathy. Only one patient with severe myelopathy due to extensive mixed-type OPLL developed a segmental weakness of the bilateral upper extremities. The overall fusion rate was 97%. Three patients with obvious spinal instability due to pseudarthrosis required reoperation. Of the graft materials used in this series, VB grafts were the most fragile. The anterior approach is an effective route for decompressing the cervical cord with OPLL. Slight asymptomatic kyphotic deformity may be encountered. Of the graft materials used in our series, VB graft was considered most fragile, and thus least optimal.
This study aimed to calculate the incidence and prevalence of ossification of the posterior longitudinal ligament (OPLL) in the cervical spine with its comorbid disability. Using an 11-year nationwide database in Taiwan (National Health Insurance Research Database), this retrospective study cohort analyzed the incidences of cervical OPLL causing hospitalization. All patients admitted for the diagnosis of OPLL, regardless of surgery, were identified. Age- and sex-specific incidences, Poisson regression, and multivariate logistic regression analysis were conducted. Between 1997 and 2007 covering 241,800,725.8 person-years, 1651 patients were admitted for OPLL. The overall incidence of OPLL-related admission was 6.1 per 1 million person-years. Specifically, male sex and older age were associated with higher OPLL incidences (both p < 0.001). Among the 1651 OPLL patients, 542 (32.8%) received conservative management, 612 (37.1%) had anterior only surgery, 353 (21.4%) had posterior only surgery, and 144 (8.7%) had anterior and posterior surgery. Eighty-five patients were moderately to severely disabled (5.2% cumulative incidence rate). The incidences of disability varied by age, in a decreasing trend, except for the 60- to 69-year-old age group (p = 0.05). Patients who received posterior-only surgery were more likely to have disability. In a large cohort of the Chinese population, the incidence of cervical OPLL-related admission is 6.1 per 1 million person-years, and the prevalence rate is 7.7 per 100,000 person-years. Higher incidences are observed in elderly and male patients, which implies the disease's degenerative nature. After adjustments for demographics, the incidences and trends of OPLL-related comorbid disability are associated with age and surgical approaches.
Case 50. Axial (left) and coronal (right) T1-weighted and Gd-diethylenetriaminepentaacetic acid-enhanced MR images obtained in a 33-year-old woman with an intracranial abscess who underwent repeated aspiration via a single bur hole. A and B: Preoperative images showing a well-defined homogeneous hypointense lesion with ring enhancement (4.9 cm in diameter) and perifocal edema in the right temporoparietal area. C and D: Images obtained 24 hours after the last aspiration, showing a decrease in the abscess size (1.9 cm in diameter) and near-complete resolution of the perilesional brain edema. E and F: Images obtained 5 months after the last aspiration showing resolution of the abscess.
Case 35. Images obtained in an 18-year-old man with a postneurosurgical intracranial abscess who underwent complete excision of abscess with craniotomy as the primary surgical therapy. A and B: Preoperative axial MR images showing a brain abscess in the right parietal area. C and D: CT scans obtained 24 hours later, showing that the abscess was completely excised. E and F: Axial MR images obtained 3 months after the operation, showing complete disappearance of the abscess. 
In this study the authors' goal was to present the clinical and imaging results of the combined surgical and medical treatment of intracranial abscesses. The authors retrospectively analyzed the data in 51 patients with intracranial abscesses who underwent surgery between January 1997 and November 2007. Patients were treated with aspiration through a single bur hole, total resection with open craniotomy, or image-guided stereotactic aspiration. Computed tomography or magnetic resonance imaging was performed approximately 24 hours after surgery to evaluate the size of the abscess and almost weekly during follow-up until the abscess and/or cerebral edema was reduced. Clinical results were analyzed using modified Rankin Scale (mRS) scores. There were 36 male and 15 female patients, and their ages ranged from 14 months to 58 years (mean 29 years). Adjacent localized cranial infection was the most common predisposing factor in 31 patients (61%). Thirty-two patients were treated by repeated aspiration via a single bur hole. Streptococcus and Staphylococcus species were isolated most frequently. No statistically significant difference between causative organisms and clinical outcome was identified (p > 0.05). Assessment of overall 1-year clinical outcomes was favorable (mRS Scores 0-2) in 76.5% of patients (39 of 51 patients). The initial neurological condition was strongly correlated with the clinical outcome (p < 0.001). A combination of surgical aspiration or removal of all abscesses > 2.5 cm in diameter, a 6-week or longer course of intravenous antibiotics, and weekly neuroimaging should yield cure rates of > 90% in patients with intracranial abscesses.
Baclofen pump infusion systems are used for the treatment of patients with severe spasticity. When symptoms do not respond to infusion rate increases, the cause may be pump malfunction or catheter obstruction. The purpose of this investigation was to review the authors' experience with indium-111 diethylene-triamine-pentaacetic acid (In-111 DTPA) scintigraphy for evaluation of baclofen infusion system function and patency and to correlate scintigraphic findings with patient treatment and outcome to determine optimal methodology and diagnostic criteria. Ten scintigraphic studies acquired in eight patients (five adults, three adolescents) were retrospectively reviewed. Imaging was routinely performed at 4, 24, 48, and 72 hours after injection of In-111 DTPA into the pump reservoir. The results of the studies were interpreted by two nuclear medicine physicians who had no knowledge of the patients' clinical history or outcome. The scintigraphic findings (for example, radiotracer detected in the basal cisterns, cervical or thoracolumbar regions, infusion catheter, and pump) were recorded and correlated with neuroimaging findings, patient history, treatment, and clinical response to therapy. In cases in which the basal cistern could be visualized at any time and those in which radiotracer was visualized in the thoracolumbar intrathecal region within 48 hours, the pump systems were functional and symptoms responded to an increase in infusion rate. One patient in whom activity was visualized in the thoracolumbar intrathecal region by 72 hours also experienced clinical improvement with a flow rate increase. Visualization of the pump alone or only the pump and the subcutaneous catheter was consistent with catheter obstruction or pump malfunction. The use of In-111 DTPA scintigraphy of intrathecal baclofen infusion systems can play an important role in determining the functional status of these systems and guiding subsequent patient care.
The purpose of this prospective study was to determine if there was a difference in the self-perceived quality of life (QOL) before and after surgery among patients with Chiari I malformations with or without syringomyelia. Most patients with Chiari I malformations report improvement in their QOL after decompression surgery; however, specific outcome data have not been empirically studied in this patient population. One hundred seventy-two consecutive patients who underwent posterior fossa decompression based on neuroimaging evidence of a Chiari I malformation with or without syringomyelia were prospectively offered participation in the study. The Sickness Impact Profile (SIP) was chosen as the instrument for data collection. Completed questionnaires were returned by 112 patients. A statistically significant improvement (p < 0.0001) in SIP scores (self-reported QOL) was noted in 84% of participants after decompression surgery. Patient age, amount of tonsillar herniation, and evidence of syringomyelia before surgery did not correlate with or adversely affect outcomes. Among 16 participants who reported worsening in their QOL, anecdotal information revealed extraneous factors unrelated to the Chiari I malformation that they perceived as negatively influencing their outcome. Among the extraneous variables noted by the participants were general health status, unrelated injury, other illnesses, and significant stress. The majority of participants who underwent posterior fossa surgery for a Chiari I malformation reported significant improvement in their QOL after surgery.
Cerebral vasospasm is a major complication of subarachnoid hemorrhage (SAH) after the rupture of an intracranial aneurysm. Although the cause of cerebral vasospasm has not been fully established, several lines of evidence suggest that the vasoconstrictor peptide endothelin (ET) may play a crucial role. In the present study the potential of TBC 11251 (TBC), a newly developed ET A receptor antagonist, to prevent and/or reverse cerebral vasospasm was examined in a well-established rabbit model of SAH. Sixty-five New Zealand White rabbits were assigned to one of six groups. Experimental SAH was induced in rabbits comprising five of the groups by injecting autologous arterial blood into the cisterna magna. The treatment groups were as follows: 1) control (no SAH); 2) SAH only; 3) SAH + placebo at 24 and 36 hours (24/36); 4) SAH + TBC (24/36); 5) SAH + placebo twice daily (BID); and 6) SAH + TBC BID. All drug-treated animals received an intravenous dosage of 5 mg/kg TBC. After 48 hours, the animals were killed by intracardiac perfusion with fixative. The brainstems were removed and the basilar arteries (BAs) were prepared for histological examination. The cross-sectional area of each BA was measured using computer-assisted videomicroscopy by an investigator blind to the group from which it came. A one-way analysis of variance and paired group mean comparisons with the post-hoc Fisher least significant difference test were used for analysis of BA diameters and physiological parameters. The model provided reliable vasospasm, with the mean BA cross-sectional area constricting from 0.388 mm ² in the control group to 0.106 mm ² (27.4% of control) in the SAH only group. Treatment with TBC (24/36) after SAH (reversal protocol) produced a mean BA area of 0.175 mm ² (44.2% of control) which, although larger than the placebo group value of 0.135 mm ² (39.9% of control), was not statistically significant. However, treatment with TBC BID (prevention protocol) produced a mean BA area of 0.303 mm ² (78.1% of control) compared with the placebo BID value of 0.134 mm ² (34.6% of control); this effect was statistically significant (p < 0.01). There were no side effects noted and no differences in the mean arterial pressures between drug and placebo groups. These findings demonstrate that systemic administration of the ET A receptor antagonist TBC significantly attenuates cerebral vasospasm after SAH when given as a preventative therapy, and they provide additional support for the role of ET in the establishment of vasospasm.
Literature review of frequency of IDH1 and IDH2 mutations in CNS and non-CNS human cancers Tumor Categories IDH1 Mutations IDH2 Mutations 
Object: The authors' goal was to review the current understanding of the underlying molecular and genetic mechanisms involved in low-grade glioma development and how these mechanisms can be targets for detection and treatment of the disease and its recurrence. Methods: On October 4, 2012, the authors convened a meeting of researchers and clinicians across a variety of pertinent medical specialties to review the state of current knowledge on molecular genetic mechanisms of low-grade gliomas and to identify areas for further research and drug development. Results: The meeting consisted of 3 scientific sessions ranging from neuropathology of IDH1 mutations; CIC, ATRX, and FUBP1 mutations in oligodendrogliomas and astrocytomas; and IDH1 mutations as therapeutic targets. Sessions consisted of a total of 10 talks by international leaders in low-grade glioma research, mutant IDH1 biology and its application in glioma research, and treatment. Conclusions: The recent discovery of recurrent gene mutations in low-grade glioma has increased the understanding of the molecular mechanisms involved in a host of biological activities related to low-grade gliomas. Understanding the role these genetic alterations play in brain cancer initiation and progression will help lead to the development of novel treatment modalities than can be personalized to each patient, thereby helping transform this now often-fatal malignancy into a chronic or even curable disease.
Object: Quality and safety are basic concerns in any medical practice. Especially in daily surgical practice, with increasing turnover and shortened procedure times, attention to these topics needs to be assured. Starting in 2007, the authors used a perioperative checklist in all elective procedures and extended the checklist in January 2011 according to the so-called team time-out principles, with additional assessment of patient identity and the planned surgical procedure performed immediately before skin incision, including the emergency cases. Methods: The advanced perioperative checklist includes parts for patient identification, preoperative assessments, team time-out, postoperative treatment, and imaging controls. All parts are signed by the responsible physician except for the team time-out, which is performed and signed by the theater nurse on behalf of the surgeon immediately before skin incision. Results: Between January 2007 and December 2010, 1 wrong-sided bur hole in an emergency case and 1 wrong-sided lumbar approach in an elective case (of 8795 surgical procedures) occurred in the authors' department. Using the advanced perioperative checklist including the team time-out principles, no error occurred in 3595 surgical procedures (January 2011-June 2012). In the authors' department all team members appreciate the chance to focus on the patient, the surgical procedure, and expected difficulties. The number of incomplete checklists and of patients not being transferred into the operating room was lowered significantly (p = 0.002) after implementing the advanced perioperative checklist. Conclusions: In the authors' daily experience, the advanced perioperative checklist developed according to the team time-out principles improves preoperative workup and the focus of the entire team. The focus is drawn to the procedure, expected difficulties of the surgery, and special needs in the treatment of the particular patient. Especially in emergency situations, the team time-out synchronizes the involved team members and helps to improve patient safety.
Outcome of decompression and/or fusion* 
Rotational occlusion of the vertebral artery (VA), or bow hunter’s syndrome, is a rare yet surgically treatable cause of vertebrobasilar insufficiency. The underlying pathology is dynamic stenosis of the VA by osteophytes, fibrous bands, or lateral disc herniation with neck rotation or extension. The authors present 2 previously unreported cases of bow hunter’s syndrome and summarize 124 cases identified in a literature review. Both patients in the new cases were treated by VA decompression and fusion of the subaxial spine. Each had > 50% occlusion of the left VA at the point of entry into the transverse foramen with a contralateral VA that ended in the posterior inferior cerebellar artery. Analyzing data from 126 cases (the 2 new cases in addition to the previously published 124), the authors report that stenosis was noted within V 1 in 4% of cases, in V 2 in 58%, in V 3 in 36%, and distal to C-1 in 2%. Patients presented in the 5th to 7th decade of life and were more often male than female. The stenotic area was decompressed in 85 (73%) of the 116 patients for whom the type of treatment was reported (V 1 , 4 [80%] of 5; V 2 , 52 [83%] of 63; V 3 /V 4 , 29 [60%] of 48). Less commonly, fusion or combined decompression and fusion was used (V 2 , 7 [11%] of 63; V 3 /V 4 , 14 [29%] of 48). Most patients reported complete resolution of symptoms. The authors conclude that patients with bow hunter’s syndrome classically have an impaired collateral blood flow to the brainstem. This condition carries an excellent prognosis with decompression, fusion, or combined surgery, and individual patient characteristics should guide the choice of therapy.
Whole-brain radiotherapy (WBRT) after resection of a single brain metastasis can cause long-term radiation toxicity. The authors evaluated the efficacy of resection and placement of 125I seeds (without concomitant WBRT) for newly diagnosed single brain metastases. In a retrospective review from two institutions (1997-2003), 15 women and 11 men (mean age 55 years) with single brain metastasis underwent gross-total resection and placement of permanent low-activity 125I seeds. Primary systemic cancer sites varied. Patients were monitored clinically and radiographically. With neuroimaging evidence of local recurrence or new distant metastasis, further treatment was administered at the physician's discretion. By the median follow-up evaluation (12 months), the local tumor control rate was 96%. Distant metastases occurred in three patients within 3 months, suggesting synchronous metastasis, and in six patients more than 3 months after treatment, indicating metachronous metastasis. Treatment in these cases included radiosurgery in seven patients, WBRT in two, and resection together with 125I seed placement in one. Two patients who suffered radiation necrosis required operative intervention (lesion diameter > 3 cm, total activity > 40 mCi). All 26 patients who had been treated using resection and placement of 125I seeds had a stable or an improved Karnofsky Performance Scale score. At the last review, nine of 16 living patients showed no evidence of treatment failure. The median actuarial survival rate was 17.8 months (Kaplan-Meier method). Permanent 125I brachytherapy applied at the initial operation without WBRT provided excellent local tumor control. Local control and patient survival rates were at least as good as those reported for resection combined with WBRT. Although the authors noted a higher incidence of distant metastases compared with that reported in other studies of initial WBRT, these metastases were generally well controlled with a combination of surgery, stereotactic radiosurgery, and, less often, WBRT. Twenty-four patients (92%) never required WBRT, thus avoiding potential long-term radiation-induced neurotoxicity.
The need for interbody fusion or stabilization after anterior cervical microdiscectomy is still debated. The objectives of this prospective randomized study were 1) to examine whether combined interbody fusion and stabilization is more beneficial than microdiscectomy only (MDO) and 2) if fusion is found to be more beneficial than MDO, to determine which is the best method of fusion by comparing the results achieved using autologous bone graft (ABG), polymethylmethacrylate (PMMA) interposition, and threaded titanium cage (TTC). A total of 125 patients with a single-level cervical disc disease were included in this prospective study. All patients were randomized and assigned to one of the four following groups: Group 1 (33 patients), MDO; Group 2 (30 patients), microdiscectomy followed by ABG; Group 3 (26 patients), microdiscectomy followed by injection of PMMA; and Group 4 (36 patients), microdiscectomy followed by placement of a TTC. Clinical outcome according to Odom criteria was summarized as 1) excellent and good or 2) satisfactory and poor. One-year follow-up examination was performed in 123 patients. Patients in the TTC group experienced a significantly better outcome 6 months after surgery (92% excellent and good results) compared with those in the MDO and ABG groups (72.7 and 66.6% excellent and good results, respectively). Twelve months after surgery there was still a significant difference in outcomes between the TTC group (94.4% excellent and good results) and the MDO group (75.5% excellent and good results). Outcome in patients treated with PMMA was comparable with that in those treated with TCC after 6 (91.6%) and 12 months (87.5%), but no segmental fusion was achieved. Differences compared with MDO and ABG were, however, not significant, which may be related to the smaller number of patients in the PMMA group. Interbody cage-assisted fusion yields a significantly better short- and intermediate-term outcome than MDO in terms of return to work, radicular pain, Odom criteria, and earlier fusion. In addition, the advantages of interbody cages over ABG fusion included better results in terms of return to work, Odom criteria, and earlier fusion after 6 months. These results suggest that interbody cage-assisted fusion is a promising therapeutic option in patients with single-level disc disease. Polymethylmethacrylate seems to be a good alternative to interbody cage fusion but is hindered by the absence of immediate fusion.
The long-term outcome of lumbar dynamic stabilization is uncertain. This study aimed to investigate the incidence, risk factors, and outcomes associated with screw loosening in a dynamic stabilization system. The authors conducted a retrospective review of medical records, radiological studies, and clinical evaluations obtained in consecutive patients who underwent 1- or 2-level lumbar dynamic stabilization and were followed up for more than 24 months. Loosening of screws was determined on radiography and CT scanning. Radiographic and standardized clinical outcomes, including the visual analog scale (VAS) and Oswestry Disability Index (ODI) scores, were analyzed with a focus on cases in which screw loosening occurred. The authors analyzed 658 screws in 126 patients, including 54 women (42.9%) and 72 men (57.1%) (mean age 60.4 ± 11.8 years). During the mean clinical follow-up period of 37.0 ± 7.1 months, 31 screws (4.7%) in 25 patients (19.8%) were shown to have loosened. The mean age of patients with screw loosening was significantly higher than those without loosening (64.8 ± 8.8 vs 59.3 ± 12.2, respectively; p = 0.036). Patients with diabetes mellitus had a significantly higher rate of screw loosening compared with those without diabetes (36.0% vs 15.8%, respectively; p = 0.024). Diabetic patients with well-controlled serum glucose (HbA1c ≤ 8.0%) had a significantly lower chance of screw loosening than those without well-controlled serum glucose (28.6% vs 71.4%, respectively; p = 0.021). Of the 25 patients with screw loosening, 22 cases (88%) were identified within 6.6 months of surgery; 18 patients (72%) had the loosened screws in the inferior portion of the spinal construct, whereas 7 (28%) had screw loosening in the superior portion of the construct. The overall clinical outcomes at 3, 12, and 24 months, measured by VAS for back pain, VAS for leg pain, and ODI scores, were significantly improved after surgery compared with before surgery (all p < 0.05). There were no significant differences between the patients with and without screw loosening at all evaluation time points (all p > 0.05). All 25 patients with screw loosening were asymptomatic, and in 6 (24%) osseous integration was demonstrated on later follow-up. Also, there were 3 broken screws (2.38% in 126 patients or 0.46% in 658 screws). To date, none of these loosened or broken screws have required revision surgery. Screw loosening in dynamic stabilization systems is not uncommon (4.7% screws in 19.8% patients). Patients of older age or those with diabetes have higher rates of screw loosening. Screw loosening can be asymptomatic and presents opportunity for osseous integration on later follow-up. Although adverse effects on clinical outcomes are rare, longer-term follow-up is required in cases in which screws become loose.
Clinical and demographic characteristics in 13 patients who underwent TNE resection of parasellar meningiomas*
Transnasal endoscopic (TNE) approaches have been proposed for the resection of anterior cranial base meningiomas. The purpose of this article was to evaluate the results of endoscopic resection of anterior cranial fossa meningiomas by reviewing available published data in addition to the authors' experience with 13 cases. The literature was searched via OVID to identify all available disaggregate data pertaining to anterior fossa meningiomas treated primarily by TNE. In addition, the authors reviewed the records of a personal series of 13 patients who underwent TNE removal of parasellar meningiomas through a pure TNE approach. Meta-analysis from studies included a total of 69 patients with adequate disaggregated data to summarize. Mean age (± SD) at surgery was 53.3 ± 13.0 years (range 27-80 years); 78% of the patients were women. Tumor size was skewed toward smaller lesions, with a mean volume of 24.4 ± 2.9 cm(3). Intraoperative impressions were of gross-total resection in 76% of cases. The most common complication reported was CSF leakage, occurring in 32% of the cases (22 of 69). The rate of CSF leakage was not affected by size (p = 0.52), location of tumor (p = 0.9), or age (p = 0.56). There was 1 death overall. The mean duration of follow-up was 21 ± 18 months. Transnasal endoscopic resection of anterior cranial base meningiomas is feasible in selected cases. Reported resection rates are adequate, although the follow-up in the reported series is too short (mean 21 months) to make definitive conclusions regarding the long-term effectiveness. Cerebrospinal fluid leakage is a common complication, although it appears not to be associated with additional morbidity except for the need for reoperation. Long-term results are necessary before considering TNE resection as a valid alternative, in selected cases, to the more established transcranial techniques.
Schematic model of IL-4R subunits. Type I IL-4R (left) consists of IL-4R and IL-2R chains (c) and is expressed in T cells and natural killer (NK) cells. Tumor cells (renal cell carcinoma [RCC], colon carcinoma [colon ca], and brain tumors) express Type II IL-4R (right), which consists of IL-4R and IL-13R1 chains. Both types of IL-4R complexes have been confirmed by reconstitution studies. 
Targeting cell surface receptors with cytotoxins or immunotoxins provides a unique opportunity for brain tumor therapy. The authors have discovered that receptors for two cytokines, interleukin (IL)-4 and IL-13, are overexpressed on tumor biopsy samples and on cell lines derived from a variety of human tumors, including brain tumors. These investigators have demonstrated that the structure of these cytokine receptors on tumor cells is different from that found on normal immune cells. In human solid tumor cells, IL-4 binds to two chains (IL-4Ra and IL-13Ra1), whereas IL- 13 binds to three chains in many solid tumor cells, including glioma cells (to IL-4Ra, IL-13Ra1, and IL-13Ra2). To target IL-4Rs and IL-13Rs, the authors generated two recombinant fusion cytotoxins composed of IL-4 or IL-13 and a mutated form of pseudomonas exotoxin (PE), which for simplicity are called IL4-PE and IL13-PE in this paper. These chimeric cytotoxins are highly toxic in vitro to human tumor cell lines and primary cell cultures, including glioma cells, and in vivo to animal models of human tumors, including gliomas. In contrast, normal cells, including immune, endothelial, and brain cells, are spared from their cytotoxic effects. Based on numerous preclinical studies, IL13-PE (also known as IL13-PE38QQR or cintredekin besudotox) has been tested in four Phase I/II clinical trials. The agent IL13-PE was administered intracranially by using convection-enhanced delivery (CED). The drug was delivered through catheters placed either directly into the tumor bed or in the peritumoral region after resection of the lesion. The CED of IL13-PE was fairly well tolerated, with a reasonable benefit/risk profile for treatment of patients with glioma. Based on Phase I/II clinical trials, the Phase III Randomized Evaluation of CED of IL13-PE Compared to Gliadel Wafer with Survival Endpoint Trial (also known as the PRECISE Trial) in patients with initial recurrence of glioblastoma multiforme has recently been completed. Patients are being monitored for safety of the agents, duration of overall survival, and quality of life.
Application of minimally invasive techniques to lumbar disc surgery has led to the development of the Microscopic Endoscopic Tubular Retractor System (METRx-MD). A prospective evaluation of results and complications was undertaken. One hundred thirty-five patients underwent surgery in which the METRx-MD system was used; most procedures were performed on an outpatient basis, and general anesthesia was induced in all cases. All patients were followed prospectively. Outcomes were measured using a visual analog scale (VAS), the Oswestry Disability Index (ODI), and the Short Form-36 (SF-36) questionnaires. Follow-up data were collected by an outside company, which also tabulated the data. Data were collected in 129 of 135 patients. Improvement was seen on the VAS (Scores 7-2), ODI (Scores 57-16), and SF-36 scales (bodily pain Scores 20-60). Patient satisfaction with results was 94% and with office services 88%. Thirty-six percent of patients returned to work at 0 to 2 weeks, 38% at 3 to 5 weeks, and 25% at 5 to 26 weeks. Hospital charges decreased by $2395 (18%). The mean operative time was 66 minutes, and the mean blood loss was 22 ml. Complications included one superficial wound infection, one discitis, three durotomies, and three cases of excessive bleeding (> 100 ml). There were five reoperations: four for recurrent disc herniations, (two ipsilateral and two contralateral to the index site) and one for spinal stenosis contralateral to the index site. Minimally invasive surgery in which the METRx-MD system is used is clinically effective and cost effective. Patient satisfaction was high. A mean per case cost savings of $2395 was realized. Complications rates were comparable with those associated with traditional microdiscectomy procedures.
Posterior petrous meningiomas (commonly termed posterior pyramid meningiomas and/or meningiomas of the posterior surface of the petrous pyramid) are the most common meningiomas of the posterior cranial fossa. They are located along the posterior surface of the temporal bone in the region of the cerebellopontine angle. They often mimic vestibular schwannomas, both clinically and on neuroimaging studies. Common clinical symptoms include hearing loss, cerebellar ataxia, and trigeminal neuropathy. The site of dural origin determines the direction of cranial nerve displacement. Total resection can be achieved in most cases with a low morbidity rate and an excellent prognosis. The authors review the surgical management of posterior petrous meningiomas.
Summary of data on early surgical procedures for CPs, 1891-1938*
Summary of data on early surgical procedures for CPs, 1891-1938* (continued)
Bivariate relationships between epidemiological, topographical, surgical, and patient outcome categories analyzed for operations for CPs, 1891-1938*
Fundamental pioneering developments during the early period of surgical treatment of CPs, 1891-1938
Object: The development of surgical procedures for the removal of craniopharyngiomas (CPs) was greatly influenced by the enormous topographical and morphological heterogeneity displayed by these lesions. In this study the authors reviewed the intracranial approaches designed to treat CPs during the early historical period (1891-1938) with the aim of finding the CP topographical and pathological features that influence patient outcomes. Methods: The authors conducted a systematic retrospective review of well-described cases of surgically treated CPs in publications from the period 1891-1938. Valuable information regarding the diagnosis of the lesion, type of craniotomy performed, CP topography, and outcome was selected from 418 reports included in medical publications from this period. The type of surgical procedure used, degree of tumor removal, CP position and histological variety, and clinical evidence of postoperative hypothalamic injury were the variables analyzed with the aim of defining their influence on the final patient outcome. Results: A collection of 160 cases was eligible for analysis. Craniopharyngioma topography was significantly related to the existence of postoperative hypothalamic damage and the degree of tumor removal achieved (p < 0.001). The infundibulo-tuberal, or not strictly intraventricular, topography was associated with the highest rate of hypothalamic injury (84%) and impossibility of tumor removal (51%). This topography also showed the worst prognosis (p = 0.001). Additional variables correlated with patient outcome were the presence of hypothalamic damage, type of surgical approach used, and degree of tumor removal. Patients having a poor outcome, suffering from permanent coma, or dying after surgery presented with symptoms of hypothalamic injury in 40% of cases (p < 0.001). The surgical approach associated with the best outcome was the transsphenoidal (58%), followed by the subfrontal (45%) and the transcallosal (45%). Subtotal resection of the lesion yielded the best postoperative results, with only 17% of patients dying or suffering from a poor outcome, in contrast to the 39% reported for gross-total removal of the lesion (p = 0.001). Conclusions: Two major variables influenced the results of early surgical experience with CPs for the period from 1891 to 1938: 1) the inaccuracy in defining CP topography with the diagnostic methods available at that time; and 2) the ignorance about the risks associated with the dissection of lesions showing tenacious adherence to the hypothalamus. The degree of functional and morphological disturbance of the hypothalamus caused by a CP remains a fundamental variable helping the surgeon to predict the risks associated with the radical excision of the tumor and patient outcome.
Humphrey Ridley, M.D. (1653–1708), is a relatively unknown historical figure, belonging to the postmedieval era of neuroanatomical discovery. He was born in the market town of Mansfield, 14 miles from the county of Nottinghamshire, England. After studying at Merton College, Oxford, he pursued medicine at Leiden University in the Netherlands. In 1688, he was incorporated as an M.D. at Cambridge. Ridley authored the first original treatise in English language on neuroanatomy, The Anatomy of the Brain Containing its Mechanisms and Physiology: Together with Some New Discoveries and Corrections of Ancient and Modern Authors upon that Subject . Ridley described the venous anatomy of the eponymous circular sinus in connection with the parasellar compartment. His methods were novel, unique, and effective. To appreciate the venous anatomy, he preferred to perform his anatomical dissections on recently executed criminals who had been hanged. These cadavers had considerable venous engorgement, which made the skull base venous anatomy clearer. To enhance the appearance of the cerebral vasculature further, he used tinged wax and quicksilver in the injections. He set up experimental models to answer questions definitively, in proving that the arachnoid mater is a separate meningeal layer. The first description of the subarachnoid cisterns, blood-brain barrier, and the fifth cranial nerve ganglion with its branches are also attributed to Ridley. This historical vignette revisits Ridley's life and academic work that influenced neuroscience and neurosurgical understanding in its infancy. It is unfortunate that most of his novel contributions have gone unnoticed and uncited. The authors hope that this article will inform the neurosurgical community of Ridley's contributions to the field of neurosurgery.
A: Lateral cervical plain x-ray film showing collapse of the C-4 VB and a marked kyphotic deformity in a patient with cervical osteomyelitis caused by methicillin-resistant S. aureus. B: Sagittal CT reconstruction obtained in the same patient, demonstrating significant prevertebral soft-tissue swelling extending from C2-6. The end plates of C-3, C-4, C-5, and C-6 are irregular and sclerotic, and collapse of the VBs compatible with osteomyelitis resulting in kyphosis is observed. Posterior to the VBs in the epidural space, soft tissue is seen from C3-6, which may represent phlegmon and/or abscess (arrow). In combination with the kyphosis, this results in spinal cord compression. 
Literature review of the microorganisms identified in cultures obtained in patients with cervical osteomyelitis Study, No. of Patients (%) 
Axial CT scan obtained through C5-6 during CT-guided biopsy sampling; a 20-gauge Chiba needle was used. Bloody fluid was aspirated that was positive in culture for Candida. 
Establishing the diagnosis of cervical osteomyelitis in a timely fashion is critical to prevent catastrophic neurological injury. In the modern imaging era, magnetic resonance imaging in particular has facilitated the diagnosis of cervical osteomyelitis, even before the onset of neurological signs or symptoms. Nevertheless, despite advancements in diagnosis, disagreement remains regarding appropriate surgical treatment. The role of instrumentation and type of graft material after cervical decompression remain controversial. The authors describe the epidemiological features, pathogenesis, and diagnostic evaluation, and the surgical and nonsurgical interventions that can be used to treat osteomyelitis of the cervical spine. They also review the current debate about the role of instrumentation in preventing spinal deformity after surgical decompression for cervical osteomyelitis. Based on this review, the authors conclude that nonsurgical therapy is appropriate if neurological signs or symptoms, instability, deformity, or spinal cord compression are absent. Surgical decompression, debridement, stabilization, and deformity correction are the goals once the decision to perform surgery has been made. The roles of autogenous graft, instrumentation, and allograft have not been clearly delineated with Class I data, but the authors believe that spinal stability and decompression override creating an environment that can be completely sterilized by antibiotic drugs.
The authors reviewed 175 low-grade hemispheric gliomas surgically treated by one surgeon (P.B.) between 1987 and 1996: 74 astrocytomas (42%), 35 oligodendrogliomas (20%), 52 mixed gliomas (30%), 12 gangliogliomas (7%), and two ependymomas (1%). Patient age ranged from 7.5 to 81.9 years (mean 39.2 years); 84 patients (48%) were males and 91 (52%) females. Postsurgical follow-up review ranged from 0.1 to 225.2 months (mean 36.2 months, median 24.9 months). Either T(2)-weighted or contrast-enhanced T(1)-weighted magnetic resonance (MR) images were used to evaluate the percentage of resection achieved and volume of residual disease postoperatively. The majority of patients (55%) had seizures as the presenting symptom, and 45% experienced preoperative symptoms for more than 12 months. Tumor enhancement was present in 21% of cases. In 66% of surgical procedures at least one of the following technical adjuncts was used: monitored local anesthesia, real-time MR imaging, stereotactic guidance with computerized tomography, three dimensional reconstruction, cortical mapping with cortical stimulation, somatosensory or visual evoked potential recording, corticography, or intraoperative ultrasound. Intraoperative MR imaging was used for 40 (22.9%) of the craniotomies and nine (5.14%) biopsies. There were no surgery-related deaths. Complications appeared in 6% of the patients. Progression to a higher-grade tumor occurred in 9.2% of patients within the 3-year follow-up period.
In this study the authors address the efficacy and safety of frameless stereotaxy in transsphenoidal surgery. One thousand transsphenoidal operations were performed at the authors' institution between June 2000 and July 2005. This series consists of a retrospective review of 176 patients entered in a prospectively obtained database who underwent frameless stereotactic transsphenoidal surgery in which magnetic resonance (MR) imaging, computerized tomography (CT) scanning, or fluoroscopic guidance was used. Of the 176 patients, 104 (59%) had suprasellar extension of their tumor, 70 (40%) had involvement of the visual apparatus, and 65 (37%) had cavernous sinus involvement. All patients underwent detailed pre- and postoperative neurological, endocrinological, radiographic, and ophthalmological follow-up evaluations. Records were reviewed retrospectively for intraoperative and postoperative complications related to the surgical approach. No instances of visual deterioration, carotid artery (CA) stenosis, or stroke were observed following transsphenoidal surgery. Only one patient sustained damage to the CA intraoperatively, and this was controlled in the operating room. Five patients (3%) required an intensive care unit stay postoperatively. Intraoperative cerebrospinal fluid leakage was encountered in 112 patients (64%) and was more frequently observed in tumors with suprasellar involvement. Frameless stereotaxy is a safe and effective modality for the treatment of recurrent or invasive sellar masses. All three frameless stereotaxy modalities provided accurate information regarding the anatomical midline and the trajectory to the sella turcica. The MR imaging, CT scanning, and fluoroscopic stereotaxy modalities all have unique advantages as well as specific limitations.
Cervical spinal cord compression managed via an anterior approach with an arthrodesis may be associated with a decreased range of motion and accelerated adjacent-segment degeneration. Artificial cervical disc replacement may address these problems. The author presents a series of 11 patients (seven men and four women, ages 31-55 years) with anterior cervical decompression and placement of a total of 15 artificial disc prostheses. Clinical and radiological follow-up review was performed at 24 hours, 6 weeks, 3 months, 6 months, and then yearly (mean follow-up period 18.4 months, range 10-32 months). There were no major complications. There was an improvement in the Nurick grade by 0.91 grades (p < 0.001) and in the Oswestry Neck Disability Index by 41.5 percentage points (p < 0.001). In one case fusion was attained at 17 months postoperatively and one patient had a transient worsening of preoperative symptoms postoperatively, with focal kyphosis. The spinal cord was decompressed on postoperative imaging in all cases. Cervical arthroplasty after anterior cervical decompression at one or more levels represents an exciting tool in the management of spinal cord compression caused by spondylotic disease or acute disc prolapse. Results obtained in this study add further weight to the potential role of cervical arthroplasty for cervical myelopathy and longer follow up is provided on a previously reported series. It is suggested that care must be taken in using this unconstrained prosthesis if there is a preexisting spinal deformity. Longer follow up will reveal any delayed problems with artificial disc implantation, but in the short to medium term, this technique offers an excellent outcome.
Progress in morphological imaging has facilitated the diagnosis of low-grade glioma (LGG) and plays a decisive role in therapeutic decisions. To date, the method of choice is contrast-enhanced MRI including T1-/T2-weighted and FLAIR sequences. However, tumor delineation and the differentiation between neoplastic and normal brain tissue can be difficult when using morphological MRI and may complicate the identification of anaplastic foci for biopsy and further treatment planning. Furthermore, therapy monitoring and the differentiation of tumor recurrence from unspecific post-therapeutic changes in the tissue are challenging. Additional information about tumor metabolism may be very helpful for the diagnostic assessment of LGG and can be provided by PET. In recent years, the PET amino acid tracer O-(2-[(18)F]-fluoroethyl)-L-tyrosine ((18)F-FET) has been clinically validated for brain tumor diagnosis. This tracer has logistical advantages over the widely used PET tracer (11)C-methyl-L-methionine due to the longer half-life of the (18)F-label (109 vs 20 minutes, respectively). Additionally, it has been demonstrated that both tracers provide comparable diagnostic information. The authors provide an overview of the recent literature regarding the value of various clinical applications of (18)F-FET PET in patients with LGG.
The prognosis for intraventricular neurocysticercosis (IVNCC) is poorer than that for parenchymal NCC, making prompt diagnosis and treatment especially important. Although active, viable intraventricular cysts produce no reaction in the host; they can cause noncommunicating hydrocephalus, the onset of which is frequently abrupt. With the death of the larva comes a local granulomatous ependymitis, generalized ventriculitis, and meningoencephalitis. The authors report on 18 patients with IVNCC (accrued from a larger case series of 62 patients with NCC treated over an 11-year period), detailing clinical presentation, neuroimaging findings, treatment, and outcome. All patients presented with hydrocephalus and/or meningitis. The most valuable diagnostic tests were magnetic resonance imaging of the brain and EITB of serum and/or cerebrospinal fluid. Treatment included albendazole and steroid therapy in all cases, and when necessary in cases requiring urgent or emergency ventriculostomy and/or surgical removal of the obstructing cyst (followed by shunt placement if indicated). An extensive review of the literature on IVNCC has been prepared, with the goal of providing the reader with the information necessary to diagnose and treat this complex and potentially fatal disease in a timely and effective manner.
Object: Various surgical approaches, including open, minimally invasive, and hybrid techniques, have gained momentum in the management of adult spinal deformity. However, few data exist on the radiographic outcomes of different surgical techniques. The objective of this study was to compare the radiographic and clinical outcomes of the surgical techniques used in the treatment of adult spinal deformity. Methods: The authors conducted a retrospective review of two adult spinal deformity patient databases, a prospective open surgery database and a retrospective minimally invasive surgery (MIS) and hybrid surgery database. The time frame of enrollment in this study was from 2007 to 2012. Spinal deformity patients were stratified into 3 surgery groups: MIS, hybrid surgery, and open surgery. The following pre- and postoperative radiographic parameters were assessed: lumbar major Cobb angle, lumbar lordosis, pelvic incidence minus lumbar lordosis (PI-LL), sagittal vertical axis, and pelvic tilt. Scores on the Oswestry Disability Index (ODI) and a visual analog scale (VAS) for both back and leg pain were also obtained from each patient. Results: Of the 234 patients with adult spinal deformity, 184 patients had pre- and postoperative radiographs and were thus included in the study (MIS, n = 42; hybrid, n = 33; open, n = 109). Patients were a mean of 61.7 years old and had a mean body mass index of 26.9 kg/m(2). Regarding radiographic outcomes, the MIS group maintained a significantly smaller mean lumbar Cobb angle (13.1°) after surgery compared with the open group (20.4°, p = 0.002), while the hybrid group had a significantly larger lumbar curve correction (26.6°) compared with the MIS group (18.8°, p = 0.045). The mean change in the PI-LL was larger for the hybrid group (20.6°) compared with the open (10.2°, p = 0.023) and MIS groups (5.5°, p = 0.003). The mean sagittal vertical axis correction was greater for the open group (25 mm) compared with the MIS group (≤ 1 mm, p = 0.008). Patients in the open group had a significantly larger postoperative thoracic kyphosis (41.45°) compared with the MIS patients (33.5°, p = 0.005). There were no significant differences between groups in terms of pre- and postoperative mean ODI and VAS scores at the 1-year follow-up. However, patients in the MIS group had much lower estimated blood loss and transfusion rates compared with patients in the hybrid or open groups (p < 0.001). Operating room time was significantly longer with the hybrid group compared with the MIS and open groups (p < 0.001). Major complications occurred in 14% of patients in the MIS group, 14% in the hybrid group, and 45% in the open group (p = 0.032). Conclusions: This study provides valuable baseline characteristics of radiographic parameters among 3 different surgical techniques used in the treatment of adult spinal deformity. Each technique has advantages, but much like any surgical technique, the positive and negative elements must be considered when tailoring a treatment to a patient. Minimally invasive surgical techniques can result in clinical outcomes at 1 year comparable to those obtained from hybrid and open surgical techniques.
A page from the book Affections Congénitales published by Dr. Lannelongue and Dr. Menard in 1891. 
In the 19th century, Dr. Odilon Marc Lannelongue was a pioneering French surgeon who introduced a surgical technique for the treatment of craniosynostosis. In 1890, Dr. Lannelongue performed correction of sagittal synostosis by strip craniectomy. From his procedure, multiple techniques have been developed and endorsed for this condition, ranging from simple suturectomies to extensive calvarial vault remodeling. In addition, even today, endoscopically aided strip craniectomy is performed as a surgical treatment of craniosynostosis. This article describes the life and works of the surgeon who revolutionized the management of craniosynostosis.
The artery of Adamkiewicz is an important radiculomedullary artery supplying the spinal cord, especially the lumbar enlargement. Anatomical knowledge of this artery is important for avoiding serious neurological complications during surgery performed in this region--for neurosurgeons and interventional radiologists treating intramedullary tumors and spinal arteriovenous malformations, traumatologists performing spinal fusions, thoracic surgeons treating aortic aneurysms, and urologists and pediatric surgeons conducting retroperitoneal dissections. However, the biography of the talented Polish pathologist Albert Adamkiewicz, after whom the landmark artery is named, has not been described adequately in the existing neurosurgical literature. The authors bring to light the historical perspective of the eponymic artery and provide a recapitulation of other significant contributions made by Adamkiewicz, mostly involving the nervous system. His research papers on the histology of neuronal tissues and neurodegenerative diseases had high scientific merit, but the discovery of the anticancer antitoxin "cancroin" and his postulation of a cancer-causing parasite he named "Coccidium sarcolytus" met with harsh criticism and eventually led to his ill fame. The biography is supplemented with a brief overview of the important surgical implications of the artery of Adamkiewicz.
The Portuguese neurologist Egas Moniz (1874–1955) is often regarded as the founder of psychosurgery. He performed the first prefrontal leukotomy in 1935—about 75 years ago—with the help of neurosurgeon Almeida Lima (1903–1985). In contrast to the psychosurgical interventions performed by the Swiss psychiatrist Gottlieb Burckhardt (1836–1907), Moniz's interventions on the white brain substance caught great attention worldwide. As a matter of fact, it was this repercussion that led to the award of the Nobel Prize for Medicine in 1949, an award that is still highly controversial today. The goal of the present article is to reconstruct the historical background of the first leukotomies, the tangible expert debate since 1935 on the indication and legitimacy of these interventions, and their contemporary and recent (ethical) evaluation. Special focus will be set on the original Portuguese literature, which has been given too little attention thus far in the English-language literature.
Cervical spondylotic myelopathy (CSM) is one of the most common spinal cord disorders in the elderly. It is usually diagnosed by MRI, but in a significant number of patients the clinical course of CSM does not correlate with the extent of the spinal cord compression. Recent studies have suggested that a distinct metabolic pattern of the cervical cord, as assessed by PET with 2-deoxy-[(18)F]fluoro-d-glucose ((18)F-FDG) may predict a patient's clinical outcome after decompressive surgery for cervical spine stenosis. The authors provide an overview of the recent literature regarding the value of PET with (18)F-FDG of the cervical cord in patients with CSM, paying attention to prognostic aspects and the potential role of inflammatory processes in the acute phase of the disease.
The supratentorial primitive neuroectodermal tumors (PNETs) are a group of highly malignant lesions primarily affecting young children. Although these tumors are histologically indistinguishable from infratentorial medulloblastoma, they often respond poorly to medulloblastoma-specific therapy. Indeed, existing molecular genetic studies indicate that supratentorial PNETs have transcriptional and cytogenetic profiles that are different from those of medulloblastomas, thus pointing to unique biological derivation for the supratentorial PNET. Due to the rarity of these tumors and disagreement about their histopathological diagnoses, very little is known about the molecular characteristics of the supratentorial PNET. Clearly, future concerted efforts to characterize the molecular features of these rare tumors will be necessary for development of more effective supratentorial PNET treatment protocols and appropriate disease models. In this article the authors review existing molecular genetic data derived from human and mouse studies, with the aim of providing some insight into the putative histogenesis of these rare tumors and the underlying transforming pathways that drive their development. Studies of the related but distinct pineoblastoma PNET are also reviewed.
In 1915, faced with 2 patients with large skull defects, W. Wayne Babcock, an obstetrician-gynecologist-turned-general surgeon, operating in a modest North Philadelphia hospital, did something extraordinary: he went to the hospital kitchen to look for a cranial graft. Based heavily on archival and other primary sources, the authors tell the remarkable tale of the "soup bone" cranioplasties of the Samaritan Hospital and place these operations within the context of the early modern American hospital.
Deep brain stimulation (DBS) is the most rapidly expanding field in neurosurgery. Movement disorders are well-established indications for DBS, and a number of other neurological and psychiatric indications are currently being investigated. Numerous contemporary opinions, reviews, and viewpoints on DBS fail to provide a comprehensive account of how this method came into being. Misconceptions in the narrative history of DBS conveyed by the wealth of literature published over the last 2 decades can be summarized as follows: Deep brain stimulation was invented in 1987. The utility of high-frequency stimulation was also discovered in 1987. Lesional surgery preceded DBS. Deep brain stimulation was first used in the treatment of movement disorders and was subsequently used in the treatment of psychiatric and behavioral disorders. Reports of nonmotor effects of subthalamic nucleus DBS prompted its use in psychiatric illness. Early surgical interventions for psychiatric illness failed to adopt a multidisciplinary approach; neurosurgeons often worked “in isolation” from other medical specialists. The involvement of neuro-ethicists and multidisciplinary teams are novel standards introduced in the modern practice of DBS for mental illness that are essential in avoiding the unethical behavior of bygone eras. In this paper, the authors examined each of these messages in the light of literature published since 1947 and formed the following conclusions. Chronic stimulation of subcortical structures was first used in the early 1950s, very soon after the introduction of human stereotaxy. Studies and debate on the stimulation frequency most likely to achieve desirable results and avoid side effects date back to the early days of DBS; several authors advocated the use of “high” frequency, although the exact frequency was not always specified. Ablative surgery and electrical stimulation developed in parallel, practically since the introduction of human stereotactic surgery. The first applications of both ablative surgery and chronic subcortical stimulation were in psychiatry, not in movement disorders. The renaissance of DBS in surgical treatment of psychiatric illness in 1999 had little to do with nonmotor effects of subthalamic nucleus DBS but involved high-frequency stimulation of the very same brain targets previously used in ablative surgery. Pioneers in functional neurosurgery mostly worked in multidisciplinary groups, including when treating psychiatric illness; those “acting in isolation” were not neurosurgeons. Ethical concerns have indeed been addressed in the past, by neurosurgeons and others. Some of the questionable behavior in surgery for psychiatric illness, including the bygone era of DBS, was at the hands of nonneurosurgeons. These practices have been deemed as “dubious and precarious by yesterday's standards.”
The benefit of the current strategy for diagnosis (magnetic resonance, [MR] imaging) and treatment (surgery, chemotherapy, radiotherapy) of gliomas, in contrast to the standard treatment in use before MR imaging and the microsurgical era, has not yet been determined. A retrospective statistical analysis was performed for all patients with glioma who underwent surgery at a single institution between 1965 and 1974 (Group I, 88 patients) or 1986 and 1995 (Group II, 249 patients). There were no major differences in symptomatology, tumor localization, and number of surgical procedures. The mean time until tumor diagnosis was significantly shorter in Group II (Group I, 48 weeks; Group II, 19.5 weeks). Also, the mean time from initial symptoms to surgery was significantly shorter for high-grade gliomas in Group II (Group I, 16.3 weeks; Group II, 11.7 weeks). For high- as well as low-grade gliomas, there was a clear reduction of the perioperative morbidity and mortality rates in Group II. Nevertheless, for the postoperative duration of survival, no significant differences were demonstrated for high- or low-grade gliomas. Based on the results of this study, the perioperative morbidity and mortality rate as well as the time from diagnosis to treatment have been remarkably reduced within the last 30 years. Nevertheless, the overall prognosis for patients with gliomas has not changed from the 1970s until today. Thus, the introduction of modern diagnostic modalities and surgical procedures has not improved the outcome in patients with glioma. Further research to improve the treatment of this disease is urgently needed.
An increasing incidence of brain cancer has been reported for the last three decades. In this study of brain cancer incidence and patient survival in the US, the authors attempt to update information on trends by examining data provided by the Surveillance, Epidemiology, and End Results (SEER) Program. Population-based data from the SEER Program were used to calculate the incidence of and survival rates for people with brain cancer. The approximate Poisson method was used to calculate relative risks for brain cancer and to determine a 95% confidence interval. Annual age-standardized incidence rates were calculated, and time-trend analysis was conducted using joinpoint regression analysis. The relative risks of brain cancer were 1.48 for men compared with women, 3.18 for elderly persons compared with young adults, 1.86 for Caucasian patients compared with African-American patients, and 1.35 for those in metropolitan counties compared with those in nonmetropolitan counties. The incidence of brain cancer increased until 1987, when the annual percentage of change reversed direction, decreasing from 1.68 to 20.44%. The elderly experienced an increase until 1985, but their rates were stable thereafter. Rising trends were noticed for glioblastoma multiforme (GBM), oligodendroglioma, anaplastic astrocytoma, medulloblastoma, and mixed glioma, and falling trends were observed for astrocytoma not otherwise specified and malignant glioma. The survival rate for patients with GBM has not shown improvement in the last two decades. Increased risk of brain cancer is associated with being male, Caucasian, elderly, and residing in a metropolitan county. The incidence rate of brain cancer in the US is gradually declining, but the rising trend of GBM combined with its poor survival rate is disconcerting and needs further exploration.
Summary of the number of cases and patient outcomes after TSS for Cushing's disease from 1993 to 2002 in the US Parameter Value 
Multivariate analysis: effect of patient and hospital characteristics on LOS following TSS for Cushing's disease Variable Odds of Prolonged LOS (OR) 95% CI 
Information about complications, patient outcomes, and mortality rate after transsphenoidal surgery (TSS) for Cushing's disease has been derived largely from single-institution series. In this study the authors report on inpatient death, morbidity, and outcomes following TSS for Cushing's disease on a national level. All patients in the Nationwide Inpatient Sample (NIS) database who had undergone transsphenoidal resection of a pituitary tumor for Cushing's disease between 1993 and 2002 were included in the study. The number of cases per year, length of stay (LOS), and rates of inpatient complications, death, and adverse outcomes (death or discharge to institution other than home) were abstracted. Univariate and multivariate analyses were performed to determine the effects of patient and hospital characteristics on outcome measures. According to the NIS, there were an estimated 3525 cases of TSS for Cushing's disease in the US between 1993 and 2002. During this period, there was a trend toward a small increase in the number of TSSs for Cushing's disease. The in-hospital mortality rate was 0.7%, and the complication rate was 42.1%. Diabetes insipidus (15%), fluid and electrolyte abnormalities (12.5%), and neurological deficits (5.6%) were the most common complications reported. Multivariate analysis showed that complications were more likely in patients with pre-operative comorbidities. Patients older than 64 years were much more likely to have an adverse outcome (odds ratio [OR] 20.8) and a prolonged hospital stay (OR 2.2). Women were less likely than men to have an adverse outcome (OR 0.3). A single postoperative complication increased the mean LOS by 3 days, more than tripled the odds of an adverse outcome, and increased the hospital charges by more than US $7000. The authors provided a national perspective on trends, inpatient complications, and outcomes after TSS for Cushing's disease in the US. Postoperative complications had a significantly negative effect on LOS, adverse outcome, and resource utilization. Advanced age and multiple preoperative comorbidities were identified as important risk factors, and their effects on patient outcomes were quantified.
Hemostatic options available to the surgeon in the late 19th and early 20th centuries were limited. The surgical ligature was limited in value to the neurological surgeon because of the unique structural composition of brain tissue as well as the approaches and operating angles used in this type of surgery. In this manuscript the authors review the options available and the evolution of surgical hemostatic techniques and electrosurgery in the late 19th and early 20th centuries and the impact of these methods on the surgical management of tumors of the brain and its coverings.
During the first half of the 19th century, warfare did not provide a background for a systematic analysis of spinal cord injury (SCI). Medical officers participating in the Peninsular and Crimean Wars emphasized the dismal prognosis of this injury, although authors of sketchy civil reports persuaded a few surgeons to operate on closed fractures. The American Medical and Surgical History of the War of the Rebellion was the first text to provide summary of results in 642 cases of gunshot wounds of the spine. The low incidence of this injury (0.26%) and the high mortality rate (55%) discouraged the use of surgery in these cases. Improvements in diagnoses and the introduction of x-ray studies in the latter half of the century enabled Sir G. H. Makins, during the Boer War, to recommend delayed intervention to remove bone or bullet fragments in incomplete injuries. The civil experiences of Elsberg and Frazier in the early 20th century promoted a meticulous approach to treatments, whereas efficient transport of injured soldiers during World War I increased the numbers of survivors. Open large wounds or cerebrospinal fluid leakage, signs of cord compression in recovering patients, delayed clinical deterioration, or intractable pain required surgical exploration. Wartime recommendations for urological and skin care prevented sepsis, and burgeoning pension systems provided specialized longterm rehabilitation. By the Armistice, the effective surgical treatment and postoperative care that had developed through decades of interaction between civil and military medicine helped reduce incidences of morbidity and dispel the hopelessness surrounding the combatant with an SCI.
The purpose of this study was to localize pathological magnetic brain activities and to analyze metabolic alterations in functionally abnormal lesions by using magnetoencephalography (MEG) and (1)H magnetic resonance (MR) spectroscopy in patients with brain tumors. The authors studied 10 healthy volunteers and seven patients who harbored common brain tumors, namely astrocytic tumors and meningioma. In spontaneous MEG the pathological brain activities (slow waves, fast waves, and spikes) were localized using a single equivalent dipole model. After the results of MEG and (1)H MR spectroscopy were superimposed onto the corresponding MR images, the signal intensities of spectroscopically visible metabolites were analyzed in the regions in which the dipoles of the pathological activities were concentrated. Increased slow-wave activity was observed in four cases, and fast-wave or spike activity was significantly increased in one case each, respectively. These pathological activities were localized at almost the same cortical areas adjacent to the bulk of tumors, where mild reduction of N-acetyl aspartate (NAA) and slight accumulation of lactate consistently existed. Preserved and metabolically active cortical areas, which are indicated by residual NAA, might be able to generate pathological magnetic activities under lactic acidosis. Such an area could be understood as a border zone between normal brain tissue and brain tissue that has been seriously damaged by tumors or associated edema, which should be intensively treated. This combination of imaging techniques gives insight into functional as well as metabolic aspects of pathological brain conditions.
The authors conducted a study of 22 skull base chordomas. A series of 22 skull base chordomas was analyzed with G banding. Subsequently, metaphase cells obtained from three tumors were reexamined using multicolor spectral karyotyping. Clonal chromosome aberrations were identified in 11 cases, all of which were recurrent tumors. Three tumors showed a remarkable similarity in cytogenetic features, and these features appear to characterize a recurring combination of nonrandom chromosome aberrations, including isochromosome 1q, gain of chromosome 7, and monosomy for chromosomes 3, 4, 10,13, and 18. Isochromosome 1q was identified as the sole recurring structural chromosome rearrangement in these tumors. The pattern of chromosome loss reported in the progression of lumbosacral chordoma also appears to be true of skull base chordomas with the additional findings of isochromosome 1q, gain of chromosome 7, and loss of chromosome 18. Skull base chordomas characterized by isochromosome 1q and monosomy 13 provide support for the concept of the loss of putative tumor suppressor loci on 1p and 13q and aggressive tumor behavior.
More refereed publications on sports-related concussion have appeared since 2000 than in all previous years combined. Three international consensus statements, documents from the National Athletic Trainers' Association (NATA) and the American College of Sports Medicine (ACSM), and entire issues of the Clinical Journal of Sport Medicine and the Journal of Athletic Training have been devoted to this subject. The object of this article is to critique the consensus statements and NATA and ACSM documents, pointing out areas of controversy.
Top-cited authors
William Couldwell
  • University of Utah
James K Liu
  • Rutgers New Jersey Medical School
Amin Kassam
  • Northwest Community Healthcare
Ricardo L Carrau
  • The Ohio State University
Carl Snyderman