Johannes van Loon

Intermediate follow-up after treatment of degenerative disc disease with the Bryan Cervical Disc Prosthesis: Single-level and bi-level

Study Design. Prospective, concurrently enrolled, multicenter trials of the Bryan Cervical Disc Prosthesis (Medtronic Sofamor Danek, Memphis, TN) were conducted for the treatment of patients with single-level and two-level (bi-level) degenerative disc disease of the cervical spine. Objectives. The studies were designed to determine whether new functional intervertebral cervical disc prosthesis can provide relief from objective neurologic symptoms and signs, improve the patient’s ability to perform activities of daily living, decrease pain, and maintain stability and segmental motion. Summary of Background Data. The concept of accelerated degeneration of adjacent disc levels as a consequence of increased stress caused by interbody fusion of the cervical spine has been widely postulated. Therefore, reconstruction of a failed intervertebral disc with functional disc prosthesis should offer the same benefits as fusion while simultaneously providing motion and thereby protecting the adjacent level discs from the abnormal stresses associated with fusion. Methods. Patients with symptomatic cervical radiculopathy and/or myelopathy underwent implantation with the Bryan prosthesis after a standard anterior cervical discectomy. At scheduled follow-up periods, the effectiveness of the device was characterized by evaluating each patient’s pain, neurologic function, and radiographically measured range of motion at the implanted level. Results. Clinical success for both studies exceeded the study acceptance criteria of 85%. At 1-year follow-up, the flexion-extension range of motion per level averaged 7.9 ± 5.3 degrees in the single-level study and 7.4 ± 5.1 degrees in the bilevel study. No devices have been explanted. Conclusions. Discectomy and implantation of the device alleviates neurologic symptoms and signs similar to anterior cervical discectomy and fusion. Radiographic evidence supports maintenance of motion. The procedure is safe and the patients recover quickly. At least 5 years of follow-up will be needed to assess the long-term functionality of the prosthesis and protective influence on adjacent levels.

Preliminary clinical experience with the Bryan Cervical Disc Prosthesis.

OBJECTIVE The concept of accelerated degeneration of adjacent disc levels as a consequence of increased stress caused by interbody fusion of the cervical spine has been widely postulated. Therefore, reconstruction of a failed intervertebral disc with a functional disc prosthesis should offer the same benefits as fusion while simultaneously providing motion and thereby protecting the adjacent level discs from the abnormal stresses associated with fusion. This study was designed to determine whether a new, functional intervertebral cervical disc prosthesis can provide relief from objective neurological symptoms and signs, improve the patient’s ability to perform activities of daily living, decrease pain, and provide stability and normal range of motion. METHODS We conducted a prospective, concurrently enrolled, multicenter trial of the Bryan Cervical Disc Prosthesis (Spinal Dynamics Corp., Mercer Island, WA) for the treatment of patients with single-level degenerative disc disease of the cervical spine. Patients with symptomatic cervical radiculopathy and/or myelopathy underwent implantation with the Bryan prosthesis after a standard anterior cervical discectomy. At scheduled follow-up periods, the effectiveness of the device was characterized by evaluating each patient’s pain, neurological function, and range of motion at the implanted level. RESULTS Analysis included data regarding 60 patients at 6 months with 30 of those patients at 1 year. Clinical success at 6 months and 1 year after implantation was 86 and 90%, respectively, exceeding the study’s acceptance criteria of 85%. These results compare favorably with the short-term clinical outcomes associated with anterior cervical discectomy and fusion reported in the literature. At 1 year, there was no measurable subsidence of the devices (based on a measurement detection threshold of 2 mm). Evidence of anterior and/or posterior device migration was detected in one patient and suspected in a second patient. There was no evidence of spondylotic bridging at the implanted disc space. The measured range of motion in flexion-extension, as determined by an independent radiologist, ranged from 1 to 21 degrees (mean range of motion, 9 ± 5 degrees). No devices have been explanted or surgically revised. CONCLUSION Discectomy and implantation of the device alleviates neurological symptoms and signs similar to anterior cervical discectomy and fusion. Radiographic evidence supports normal range of motion. The procedure is safe and the patients recover quickly. Restrictive postoperative management is not necessary. However, only after long-term follow-up of at least 5 years will it become clear whether the device remains functional, thus confirming these early favorable results. In addition, the influence on adjacent motion segments can be assessed after at least 5 years of follow-up.

Postoperative Adjuvant Dendritic Cell–Based Immunotherapy in Patients with Relapsed Glioblastoma Multiforme

Purpose: To investigate the therapeutic role of adjuvant vaccination with autologous mature dendritic cells (DC) loaded with tumor lysates derived from autologous, resected glioblastoma multiforme (GBM) at time of relapse. Experimental Design: Fifty-six patients with relapsed GBM (WHO grade IV) were treated with at least three vaccinations. Children and adults were treated similarly in three consecutive cohorts, with progressively shorter vaccination intervals per cohort. Feasibility and toxicity were assessed as well as effect of age, extent of resection, Karnofsky Performance Score, and treatment cohort on the progression-free (PFS) and overall survival (OS) using univariable and multivariable analysis. Results: Since the prevaccine reoperation, the median PFS and OS of the total group was 3 and 9.6 months, respectively, with a 2-year OS of 14.8%. Total resection was a predictor for better PFS both in univariable analysis and after correction for the other covariates. For OS, younger age and total resection were predictors of a better outcome in univariable analysis but not in multivariable analysis. A trend to improved PFS was observed in favor of the faster DC vaccination schedule with tumor lysate boosting. Vaccine-related edema in one patient with gross residual disease before vaccination was the only serious adverse event. Conclusion: Adjuvant DC-based immunotherapy for patients with relapsed GBM is safe and can induce long-term survival. A trend to PFS improvement was shown in the faster vaccination schedule. The importance of age and a minimal residual disease status at the start of the vaccination is underscored.

Anatomy of the Anterior Temporal Lobe and the Frontotemporal Region Demonstrated by Fiber Dissection

OBJECTIVE: The white matter structure of the anterior temporal lobe and the frontotemporal region is complex and not well appreciated from the available neurosurgical literature. The fiber dissection method is an excellent means of attaining a thorough knowledge of the three-dimensional structure of the white matter tracts. This study was performed to demonstrate the usefulness of the dissection technique in understanding the white matter anatomy and the effects of current surgical approaches on the subcortical structure of the region. METHODS: Seventeen brain specimens obtained at routine autopsy were dissected by use of Klinglers fiber dissection technique after preparation by fixation and freezing. The dissections were performed with an operating microscope and followed a stepwise pattern of progressive white matter dissection. RESULTS: The dissection is described in an orderly fashion showing the white matter tracts of the anterior temporal lobe and the frontotemporal region. An insight is gained into the three-dimensional course of the anterior loop of the optic radiation, the temporal stem, the anterior commissure, and the ansa peduncularis. CONCLUSION: The anterior temporal lobe and the frontotemporal region contain several important white matter tracts that can be uniquely understood by performing a white matter dissection of the region. Surgical procedures on the anterior temporal lobe differ substantially as to their repercussions on the subcortical white matter tract anatomy, as shown by the findings in this study.

Early endovascular treatment of ruptured cerebral aneurysms in patients in very poor neurological condition.

OBJECTIVE In patients in very poor neurological condition (World Federation of Neurosurgical Societies Grade V) with aneurysmal subarachnoid hemorrhage, early surgery to prevent rebleeding and to allow appropriate treatment of complications is often difficult. The aim of the present study was to evaluate whether early endovascular treatment followed by aggressive proactive treatment of complications (prophylactic hypervolemic hemodilution, hypertensive treatment in the event of systemic hypotension, and appropriate treatment of intracranial hypertension) is an acceptable management strategy for these patients. METHODS We prospectively studied 11 consecutive patients who presented with acutely ruptured aneurysms and were in very poor neurological condition after resuscitation (World Federation of Neurosurgical Societies Grade V) but did not have a significant intracerebral hemorrhage. These patients received endovascular treatment with Guglielmi detachable coils (Boston Scientific/Target, Fremont, CA). Follow-up consisted of a clinical evaluation based on the Glasgow Outcome Scale. A control angiogram was obtained after 6 months in patients with favorable outcomes to evaluate the occlusion of the aneurysm. RESULTS There were no deaths or complications directly related to the procedure. Two patients died as a consequence of increased intracranial pressure. The mean follow-up of the surviving patients was 12 months. Two patients had early rebleeding after the coiling and required further treatment. Four patients had good outcomes, two patients were moderately disabled, and three patients were severely disabled. CONCLUSION This study demonstrates that early endovascular treatment of acutely ruptured cerebral aneurysms in patients evaluated as World Federation of Neurosurgical Societies Grade V allows for aggressive treatment of intracranial hypertension and vasospasm. More than half of the patients had favorable outcomes. Therefore, early endovascular treatment seems to be a valuable alternative to early surgery in patients who present with a very poor clinical grade after subarachnoid hemorrhage. The results of this study are promising but must be interpreted with caution, because a small number of patients were studied.

Selectivity for three-dimensional contours and surfaces in the anterior intraparietal area

The macaque anterior intraparietal area (AIP) is crucial for visually guided grasping. AIP neurons respond during the visual presentation of real-world objects and encode the depth profile of disparity-defined curved surfaces. We investigated the neural representation of curved surfaces in AIP using a stimulus-reduction approach. The stimuli consisted of three-dimensional (3-D) shapes curved along the horizontal axis, the vertical axis, or both the horizontal and the vertical axes of the shape. The depth profile was defined solely by binocular disparity that varied along either the boundary or the surface of the shape or along both the boundary and the surface of the shape. The majority of AIP neurons were selective for curved boundaries along the horizontal or the vertical axis, and neural selectivity emerged at short latencies. Stimuli in which disparity varied only along the surface of the shape (with zero disparity on the boundaries) evoked selectivity in a smaller proportion of AIP neurons and at considerably longer latencies. AIP neurons were not selective for 3-D surfaces composed of anticorrelated disparities. Thus the neural selectivity for object depth profile in AIP is present when only the boundary is curved in depth, but not for disparity in anticorrelated stereograms.

Selectivity for Three-Dimensional Shape and Grasping-Related Activity in the Macaque Ventral Premotor Cortex

Anatomical studies indicate that area F5 in the macaque ventral premotor cortex consists of three different sectors. One of these is F5a in the posterior bank of the inferior arcuate sulcus, but no functional characterization of F5a at the single-cell level exists. We investigated the neuronal selectivity for three-dimensional (3D) shape and grasping activity in F5a. In contrast to neighboring regions F5p and 45B, the great majority of F5a neurons showed selectivity for disparity-defined curved surfaces, and most neurons preserved this selectivity across positions in depth, indicating higher-order disparity selectivity. Thus, as predicted by monkey fMRI data, F5a neurons showed robust 3D-shape selectivity in the absence of a motor response. To investigate the relationship between disparity selectivity and grasping activity, we recorded from 3D-shape-selective F5a neurons during a visually guided grasping task and during grasping in the dark. F5a neurons encoding the depth profile of curved surfaces frequently responded during grasping of real-world objects in the light, but not in the dark, whereas nearby neurons were also active in the dark. The presence of 3D-shape-selective and “visual-dominant” neurons demonstrates that the F5a sector is distinct from neighboring regions of ventral premotor cortex, in line with recent anatomical connectivity studies.

Meox2/Tcf15 Heterodimers Program the Heart Capillary Endothelium for Cardiac Fatty Acid Uptake

Background— Microvascular endothelium in different organs is specialized to fulfill the particular needs of parenchymal cells. However, specific information about heart capillary endothelial cells (ECs) is lacking. Methods and Results— Using microarray profiling on freshly isolated ECs from heart, brain, and liver, we revealed a genetic signature for microvascular heart ECs and identified Meox2/Tcf15 heterodimers as novel transcriptional determinants. This signature was largely shared with skeletal muscle and adipose tissue endothelium and was enriched in genes encoding fatty acid (FA) transport–related proteins. Using gain- and loss-of-function approaches, we showed that Meox2/Tcf15 mediate FA uptake in heart ECs, in part, by driving endothelial CD36 and lipoprotein lipase expression and facilitate FA transport across heart ECs. Combined Meox2 and Tcf15 haplodeficiency impaired FA uptake in heart ECs and reduced FA transfer to cardiomyocytes. In the long term, this combined haplodeficiency resulted in impaired cardiac contractility. Conclusions— Our findings highlight a regulatory role for ECs in FA transfer to the heart parenchyma and unveil 2 of its intrinsic regulators. Our insights could be used to develop new strategies based on endothelial Meox2/Tcf15 targeting to modulate FA transfer to the heart and remedy cardiac dysfunction resulting from altered energy substrate usage.

Three-dimensional shape coding in grasping circuits: A comparison between the anterior intraparietal area and ventral premotor area f5a

Depth information is necessary for adjusting the hand to the three-dimensional (3-D) shape of an object to grasp it. The transformation of visual information into appropriate distal motor commands is critically dependent on the anterior intraparietal area (AIP) and the ventral premotor cortex (area F5), particularly the F5p sector. Recent studies have demonstrated that both AIP and the F5a sector of the ventral premotor cortex contain neurons that respond selectively to disparity-defined 3-D shape. To investigate the neural coding of 3-D shape and the behavioral role of 3-D shape-selective neurons in these two areas, we recorded single-cell activity in AIP and F5a during passive fixation of curved surfaces and during grasping of real-world objects. Similar to those in AIP, F5a neurons were either first- or second-order disparity selective, frequently showed selectivity for discrete approximations of smoothly curved surfaces that contained disparity discontinuities, and exhibited mostly monotonic tuning for the degree of disparity variation. Furthermore, in both areas, 3-D shape-selective neurons were colocalized with neurons that were active during grasping of real-world objects. Thus, area AIP and F5a contain highly similar representations of 3-D shape, which is consistent with the proposed transfer of object information from AIP to the motor system through the ventral premotor cortex.

What the neurosurgeon should know about hemangioblastoma, both sporadic and in Von Hippel‑Lindau disease: A literature review

Background: Hemangioblastomas are associated with Von Hippel-Lindau disease (VHLD) in 10-40% of cases. Based upon a literature review we state the core features the neurosurgeon should be aware of. Methods: We performed a selective literature (Cochrane and Medline) search for hemangioblastoma, both sporadic and VHL associated. We reviewed general characteristics (epidemiology, symptomatology, diagnosis, and management) and focused on follow-up as well as screening modalities for sporadic and VHL associated lesions. Results: Based upon our literature search, we established guidelines for screening and follow-up in both sporadic and VHL associated hemangioblastoma patients. Conclusions: Screening for retinal angiomas, abdominal masses, and pheochromocytomas as well as genetic analysis is recommended for every patient with a newly diagnosed hemangioblastoma. Follow-up is by magnetic resonance imaging (MRI) of the clinical neuronal region at 6 and at 12-24 months postoperatively. For VHL-associated hemangioblastomas yearly investigation for craniospinal hemangioblastoma by MRI and yearly screening and follow-up for retinal angiomas is recommended. Annual abdominal ultrasound with triennial computed tomography (CT) imaging for abdominal masses is postulated. Annual audiometry is to be performed for possible endolymphatic sac tumor, detailed radiographic imaging of the skull base should be performed upon abnormality in auditory testing. Investigations for cystadenomas of the epidydimis and broad ligament only are mandatory on indication. Annual investigation for pheochromocytoma is recommended.