bluuebunny/crossref_metadata_2025 huggingface dataset:
Current state of the art in the diagnosis and surgical treatment of Cushing disease: early experience with a purely endoscopic endonasal technique
Authors: Dehdashti Amir R. , Gentili Fred
Published: January 2008

Object

Transsphenoidal pituitary surgery is the primary therapy for Cushing disease because of its potential to produce lasting remission without the need for long-term drug or hormone replacement therapy. The authors evaluated the current role of pure endoscopic endonasal pituitary surgery in the treatment of Cushing disease.

Methods

Twenty-five patients underwent pure endoscopic surgery for confirmed Cushing disease. Thirteen patients had microadenomas and seven had macroadenomas; magnetic resonance images obtained in five patients were only suspicious or nondiagnostic, and thus they underwent inferior petrosal sinus sampling. Two patients had evidence of cavernous sinus involvement. Final histological results were consistent with adrenocorticotropin hormone (ACTH)–secreting adenoma in 20 patients.

Results

Twenty patients (80%) had clinical remission and laboratory confirmation of hypocortisolemia (serum cortisol < 100 nmol/L requiring substitution therapy), suppression to low-dose dexamethasone, and normal 24-hour urinary free cortisol. The median follow-up period was 17 months (range 3–32 months). There was no recurrence at the time of the last follow-up. Three patients presented with new anterior pituitary deficiency, but no one had permanent diabetes insipidus. In one patient a cerebrospinal fluid leak developed but later resolved following lumbar drainage. Treatment failure was attributable to involvement of the cavernous sinus in two patients, incomplete tumor removal in one, negative exploration in one, and nodular corticotroph hyperplasia of the pituitary gland in one.

Conclusions

Early results indicated that endoscopic endonasal surgery is a safe and effective treatment for ACTH-producing adenomas. The rate of remission in this study is comparable to those in previous series, and the rate of major postoperative complications is extremely low. Further studies with a larger number of patients and longer follow-ups are required to determine whether this more minimally invasive pure endoscopic approach should become the standard of care for the surgical treatment of Cushing disease.
Brain atrophy and cognitive deficits in Cushing's disease
Authors: Patil Chirag G. , Lad Shivanand P. , Katznelson Laurence , Laws Edward R.
Published: January 2008

✓ Cushing's disease is associated with brain atrophy and cognitive deficits. Excess glucocorticoids cause retraction and simplification of dendrites in the hippocampus, and this morphological change probably accounts for the hippocampal volume loss. Mechanisms by which glucocorticoids affect the brain include decreased neurogenesis and synthesis of neurotrophic factors, impaired glucose utilization, and increased actions of excitatory amino acids. In this review, the timing, pathology, and pathophysiology of the brain atrophy in Cushing's disease are discussed. The correlation of atrophy with cognitive deficits and its reversibility is also reviewed.
Nelson syndrome: comprehensive review of pathophysiology, diagnosis, and management
Authors: Banasiak Magdalena J. , Malek Ali R.
Published: January 2008

✓Nelson syndrome (NS) is a rare clinical manifestation of an enlarging pituitary adenoma that can occur following bilateral adrenal gland removal performed for the treatment of Cushing disease. It is characterized by excess adreno-corticotropin secretion and hyperpigmentation of the skin and mucus membranes. The authors present a comprehensive review of the pathophysiology, diagnosis, and management of NS. Corticotroph adenomas in NS remain challenging tumors that can lead to significant rates of morbidity and mortality. A better understanding of the natural history of NS, advances in neurophysiology and neuroimaging, and growing experience with surgical intervention and radiation have expanded the repertoire of treatments. Currently available treatments include surgical, radiation, and medical therapy. Although the primary treatment for each tumor type may vary, it is important to consider all of the available options and select tthe one that is most appropriate for the individual case, particularly in cases of lesions resistant to intervention.
Immediate and midterm follow-up results of using an electrodetachable, fully retrievable SOLO stent system in the endovascular coil occlusion of wide-necked cerebral aneurysms
Authors: Yavuz Kivilcim , Geyik Serdar , Pamuk Almila Gulsun , Koc Osman , Saatci Isil , Cekirge H. Saruhan
Published: January 2008

Object

Stent-assisted embolization is an alternative endovascular treatment method for wide-necked intracranial aneurysms. Currently available stents have the limitations of poor radial force, difficult delivery systems, and lack of full retrievability. The authors report on their preliminary experience with the use of a new, fully retrievable, self-expanding neurovascular stent, which has a high radial force and easy delivery system, combined with coil or Onyx embolization for the treatment of wide-necked aneurysms, including 6-month follow-up data.

Methods

Fifteen patients with 18 wide-necked intracranial aneurysms were treated using the SOLO stent system and detachable platinum coils. Aneurysms were located at the posterior communicating artery (seven lesions), midbasilar artery (one lesion), internal carotid artery (ICA) bifurcation (one lesion), ICA–ophthalmic artery segment (eight lesions), and posterior cerebral artery (one lesion). Eleven aneurysms were small, six were large, and one was giant. Only one of these aneurysms was in the acute stage of subarachnoid hemorrhage; balloon remodeling alone failed to keep the coils in the aneurysm sac.

Results

Only one stent required retrieving and repositioning after it had been fully deployed, and retrieval was easy and successful. No thromboembolic complication, dissection/rupture, or vasospasm occured during stent placement. Follow-up angiograms obtained at 6 months posttreatment in the 18 aneurysms demonstrated that all stents were patent with no evidence of intimal hyperplasia or stenosis. In all cases but one, 100% lesion occlusion was observed at the 6-month control angiography examination. Only one aneurysm had recanalized.

Conclusions

The fully retrievable self-expandible SOLO stent is a feasible, secure, and effective system with a high radial force and ease of delivery in treating wide-necked intracranial aneurysms in combination with coil embolization.
Thrombus organization and healing in the swine experimental aneurysm model. Part I. A histological and molecular analysis
Authors: Lee Daniel , Yuki Ichiro , Murayama Yuichi , Chiang Alexander , Nishimura Ichiro , Vinters Harry V. , Wang Chiachien J. , Nien Yih-Lin , Ishii Akira , WU Benjamin M. , Viñuela Fernando
Published: January 2008

Object

The authors describe the process of thrombus organization in the swine surgical aneurysm model.

Methods

Lateral carotid artery aneurysms with immediately induced thrombosis were created in 31 swine for a time-course study. Aneurysms were evaluated at 1, 3, 7, 14, 30, and 90 days after they were created. Histological analyses included quantitative immunohistochemical studies and evaluation of collagen deposition. Complementary DNA microarray analysis was performed for gene expression profiling. The lists of up- and downregulated genes were cross-matched with lists of genes known to be associated with cytokines or the extracellular matrix. The expression of selected genes was quantified using real-time polymerase chain reaction. Functional clustering was performed with the Expression Analysis Systematic Explorer (EASE) bioinformatics package.

Results

Histological analysis demonstrated leukocyte and macrophage infiltration in the thrombus at Day 3, myofibroblast infiltration at Days 7 to 14, and progressive collagen deposition and contraction thereafter. Tissue organization occurred in a centripetal fashion. A previously undescribed reticular network of connective tissue was observed at the periphery of the aneurysm at Day 3. Macrophages appeared critical to this thrombus organization. A total of 1109 genes were significantly changed from reference time zero during the time course: CXCL14, which produces a monocyte-specific chemokine, was upregulated over 100-fold throughout the time course; IGF1 was upregulated fourfold at Day 7, whereas IGFBP2 was downregulated approximately 50% at Days 7 and 14. Osteopontin (SPP1) upregulation increased from 30-fold at Day 30 to 45-fold at Day 14. The EASE analysis yielded eight functional classes of gene expression.

Conclusions

This investigation provides a detailed histological and molecular analysis of thrombus organization in the swine aneurysm model. The companion study will describe the effect of embolic bioabsorbable polymers on this process.
Efficacy of nonviral gene transfer in the canine brain
Authors: Oh Seunguk , Pluhar G. Elizabeth , McNeil Elizabeth A. , Kroeger Kurt M. , Liu Chunyan , Castro Maria G. , Lowenstein Pedro R. , Freese Andrew , Ohlfest John R.
Published: January 2008

Object

The purpose of this study was to evaluate the gene transfer capability and tolerability of plasmid DNA/poly-ethylenimine (PEI) complexes in comparison with adenovirus and naked plasmid DNA in the canine brain.

Methods

Plasmid or adenoviral vectors encoding firefly luciferase were injected directly into the cerebral parenchyma of five adult dogs at varying doses and volumes. Serial physical and neurological examinations, as well as blood and cerebrospinal fluid (CSF) analyses, were conducted before and after the surgery for 3 days. Three days after gene delivery, a luciferase activity assay and immunofluorescence analysis were used to test the brain tissue for gene expression.

Results

Injection into the brain parenchyma resulted in gene transfer throughout the cerebrum with every vector tested. Luciferase expression was highest when adenovirus vectors were used. Injection of plasmid DNA/PEI complexes and naked DNA resulted in similar levels of luciferase expression, which were on average 0.5 to 1.5% of the expression achieved with adenovirus vectors. Immunofluorescent microscopy analysis revealed that plasmid DNA/PEI complexes transduced mainly neurons, whereas adenovirus transduced mainly astrocytes. No significant acute side effects or neurological complications were observed in any of the dogs. Mononuclear cell counts significantly increased in the CSF after adenovirus injection and modestly increased after injection of plasmid DNA/PEI complexes, suggesting that a mild, acute inflammatory response occurred in the central nervous system (CNS).

Conclusions

Compared with rodent models that are limited by very small brains, the dog is an excellent preclinical model in which to assess the distribution and safety of emerging gene transfer technologies. In this study, short-term gene transfer was evaluated as a prelude to long-term expression and safety studies. The authors conclude that the viral and nonviral vectors tested were well tolerated and effective at mediating gene transfer throughout a large portion of the canine brain. The nonviral plasmid vectors were less effective than adenovirus, yet they still achieved appreciable gene expression levels. Due to reduced gene transfer efficiency relative to viral vectors, nonviral vectors may be most useful when the expressed protein is secreted or exerts a bystander effect. Nonviral vectors offer an alternative means to genetically modify cells within the CNS of large mammals.
Intracranial hypotension caused by leakage of cerebrospinal fluid from the thecal sac after lumboperitoneal shunt placement
Authors: Liao Yaping Joyce , Dillon William P. , Chin Cynthia T. , McDermott Michael W. , Horton Jonathan C.
Published: January 2008

✓The authors describe a newly recognized complication of lumboperitoneal (LP) shunt placement, namely, intracranial hypotension from leakage of cerebrospinal fluid (CSF) through a defect in the lumbar dura created by the shunt catheter. They report on a 47-year-old obese woman with idiopathic intracranial hypertension who underwent routine placement of an LP shunt. Following surgery, her headache became worse. Two radionuclide shunt studies showed no anterograde tracer flow, suggesting either obstruction or a leak. After shunt reservoir manometry indicated low pressure, spinal magnetic resonance (MR) imaging was performed. The MR images revealed a CSF leak from the lumbar thecal sac. A computed tomography (CT) myelogram, performed by injection into the shunt reservoir, confirmed the presence of a leak by showing extravasation of contrast agent into the epidural space. The patient was treated by application of a CT-guided blood patch at the leak site. Catheter-associated CSF leak is an unusual cause of intracranial hypotension that can occur following LP shunt placement. This case report outlines the clinical features of this condition, documents the neuroradiological findings, and demonstrates successful treatment with a blood patch.
Anaplastic astrocytoma and anaplastic oligodendroglioma occurring 6 years after subtotal resection of a central neurocytoma
Authors: Kanamori Masayuki , Kumabe Toshihiro , Watanabe Mika , Tominaga Teiji
Published: January 2008

✓The authors present the case of a 51-year-old man who presented with an anaplastic astrocytoma and anaplastic oligo-dendroglioma that developed 6 years after subtotal resection of a central neurocytoma in his right lateral ventricle. He had received neither radiation therapy nor chemotherapy after the original resection. On readmission, neuroimaging revealed a mass in the right parietal lobe and a diffuse lesion in the right temporal lobe, insula, and corona radiata. Because both lesions extended to the right lateral ventricle wall, they were regarded as recurrent rather than metachronous tumors. Histological examination revealed anaplastic oligodendroglioma in the parietal lobe and anaplastic astrocytoma in the insula. One year later, the anaplastic astrocytoma was found to have transformed into a glioblastoma multiforme. Fluorescence in situ hybridization analysis and immunohistochemical examinations detected deletions of the 1p36 and 19q13 loci, and nuclear accumulation of TP53 protein in the anaplastic oligodendroglioma but not in the glioblastoma multiforme. These findings suggest that central neurocytoma or progenitor cells have the potential for oligodendrocytic and astrocytic transformation with different genetic aberrations.
Intraoperative transaneurysmal coil-assisted clip occlusion of a complex anterior communicating artery aneurysm
Authors: Krayenbühl Niklaus , Krisht Ali F.
Published: January 2008

✓The combination of surgical and endovascular treatment for complex intracranial aneurysms has previously been used in a staged fashion. To perfect the clipping process of a complex anterior communicating artery aneurysm and to avoid a second staged procedure, the authors used a method of direct intraoperative transaneurysmal coil-assisted clip occlusion of the aneurysm.

To the authors' knowledge this is the first time direct intraoperative transaneurysmal coil-assisted clip occlusion has been reported. It should be kept in mind as one of the options to help in complete obliteration of complex intracranial aneurysms.
Intracerebral Hematoma Lysis
Authors: Rohde Veit , Samadani Uzma
Published: January 2008

Object

Currently no adequate surgical treatment exists for spontaneous intracerebral hemorrhage (ICH). Implantable polymers can be used effectively to deliver therapeutic agents to the local site of the pathological process, thus reducing adverse systemic effects. The authors report the use of stereotactically implanted polymers loaded with tissue plasminogen activator (tPA) to induce lysis of ICH in a rabbit model.

Methods

Ethylene vinyl acetate (EVAc) polymers were loaded with bovine serum albumin (BSA) only or with BSA plus tPA. In vitro pharmacokinetic (three polymers) and thrombolysis (12 polymers) studies were performed. For the in vivo study, 12 rabbits were fixed in a stereotactic frame, and 0.2 ml of clotted autologous blood was injected into the right frontal lobe parenchyma. After 20 minutes, control BSA polymers were stereotactically implanted at the hemorrhage site in six rabbits, and experimental BSA plus tPA polymers were implanted in six rabbits. Animals were killed at 3 days, and blood clot volume was assessed.

The pharmacokinetic study showed release of 146 ng of tPA over 3 days. The tPA activity correlated with in vitro thrombolysis. In the in vivo study, the six animals treated with tPA polymers had a mean (±standard error of the mean [SEM]) thrombus volume of 1.43 ±0.29 mm3 at 3 days, whereas the six animals treated with blank (BSA-only) polymers had a mean (±SEM) thrombus volume of 19.99 ±3.74 mm3 (p <0.001).

Conclusions

Ethylene vinyl acetate polymers release tPA over the course of 3 days. Stereotactic implantation of tPA-loaded EVAc polymers significantly reduced ICH volume. Polymers loaded with tPA may be useful clinically for lysis of ICH without the side effects of systemic administration of tPA.
Brachial plexus injuries: outcome following neurotization with intercostal nerve
Authors: Moiyadi Aliasgar Vajihuddin , Devi Bhagavatula Indira , Sivaraman Nair K. P.
Published: January 2008

Object

Brachial plexus root avulsion injuries, which are devastating, usually result from high-speed accidents. Nerve transfer provides hope for successful treatment of this difficult set of injuries. Nevertheless, the controversies regarding indications, techniques, and outcome of the various available surgical procedures continue.

Methods

A retrospective analysis was performed in 51 patients (43 male and eight female patients) with brachial plexus injuries who underwent neurotization at the authors' institute between 1997 and 2003. Clinical, electrophysiological, and imaging data were used to identify the type and pattern of involvement of the various elements of the plexus. The mean duration of denervation was 6.4 months (range 2–24 months). Outcome was computed in terms of the overall improvement in power of the target muscle as well as the functional usefulness of such recovery.

Results

There were 50 supraclavicular injuries (25 preganglionic, eight postganglionic, and 17 mixed). One patient had an infraclavicular (posterior spinal cord) injury. Pan–brachial plexus injury with a flail upper limb was the most common pattern. Overall, 55 nerves were neurotized—33 musculocutaneous, 18 axillary, and two each for ulnar and radial nerves (47 single and four double neurotizations—by using intercostal nerve donors in the majority of cases. Adequate follow-up data were available in 36 patients (38 nerves) and these were used for the analysis of outcome. Overall, 58.3% of patients had improvement, and of these 62% achieved useful recovery. This accounted for 36% of overall useful recovery. Multiple logistic regression analysis revealed that regardless of age, sex, mode and pattern of injury, and recipient nerve, the duration of denervation showed a trend toward significance that correlated with overall (but not useful) improvement. The critical duration of denervation was 5.5 months.

Conclusions

Neurotization for brachial plexus root avulsion injuries is a viable option. Early detection and intervention (within 5.5 months) leads to a better overall recovery.
Patient outcome after common peroneal nerve decompression
Authors: Humphreys Douglas B. , Novak Christine B. , Mackinnon Susan E.
Published: January 2008

Object

This study examines common peroneal nerve decompression and its effect on nerve function.

Methods

Fifty-one peroneal nerve decompressions were retrospectively reviewed. All patients were evaluated preoperatively and postoperatively for motor and sensory function of the peroneal nerve as well as for pain.

Results

Postoperatively, 40 (83%) of 48 patients who had preoperative motor weakness had improvement in motor function. Likewise, 23 (49%) of 47 patients who had sensory disturbances and 26 (84%) of 31 patients who had preoperative pain improved after surgical decompression of the peroneal nerve.

Conclusions

Common peroneal nerve decompression is a useful procedure to improve sensation and strength as well as to decrease pain.
Treatment of traumatic brain injury in rats with erythropoietin and carbamylated erythropoietin
Authors: Mahmood Asim , Lu Dunyue , Qu Changsheng , Goussev Anton , Zhang Zheng Gang , Lu Chang , Chopp Michael
Published: January 2008

Object

This study was designed to investigate the neuroprotective properties of recombinant erythropoietin (EPO) and carbamylated erythropoietin (CEPO) administered following traumatic brain injury (TBI) in rats.

Methods

Sixty adult male Wistar rats were injured with controlled cortical impact, and then EPO, CEPO, or a placebo (phosphate-buffered saline) was injected intraperitoneally. These injections were performed either 6 or 24 hours after TBI. To label newly regenerating cells, bromodeoxyuridine was injected intraperitoneally for 14 days after TBI. Blood samples were obtained on Days 1, 2, 3, 7, 14, and 35 to measure hematocrit. Spatial learning was tested using the Morris water maze. All rats were killed 35 days after TBI. Brain sections were immunostained as well as processed for the enzyme-linked immunosorbent assay to measure brain-derived neurotrophic factor (BDNF).

Results

A statistically significant improvement in spatial learning was seen in rats treated with either EPO or CEPO 6 or 24 hours after TBI (p < 0.05); there was no difference in the effects of EPO and CEPO. Also, these drugs were equally effective in increasing the number of newly proliferating cells within the dentate gyrus at both time points. A statistically significant increase in BDNF expression was seen in animals treated with both EPO derivatives at 6 or 24 hours after TBI. Systemic hematocrit was significantly increased at 48 hours and 1 and 2 weeks after treatment with EPO but not with CEPO.

Conclusions

These data demonstrate that at the doses used, EPO and CEPO are equally effective in enhancing spatial learning and promoting neural plasticity after TBI.
Endoscopic stent placement for treatment of secondary bilateral occlusion of the Monro foramina following endoscopic third ventriculostomy in a patient with aqueductal stenosis
Authors: Mori Hiroshi , Koike Toshiro , Fujimoto Tsuyoshi , Nishiyama Kenichi , Yoshimura Junichi , Tanaka Ryuichi
Published: January 2008

✓ Nontumoral bilateral occlusion of the Monro foramina is a rare clinical condition. Treatment includes shunt placement, endoscopic procedures, or both. The authors describe the case of a 22-year-old woman who had previously undergone placement of a ventriculoperitoneal shunt via a right frontal approach for management of triventricular dilation due to aqueductal stenosis. Six years postoperatively she presented with right-sided slit-ventricle syndrome and stenosis of the right Monro foramen, which was treated with an endoscopic third ventriculostomy and fenestration of the septum pellucidum. Two years later she presented with bilateral lateral ventricular dilation. Inspection of the right lateral ventricle with a fiberscope revealed occlusion of the septum pellucidum fenestration; on observation, the right Monro foramen was covered by thick, tough granulation tissue and the left was occluded by thin membranous tissue. Repeated fenestration of the septum pellucidum and left Monro foraminoplasty were therefore performed by perforating this thin tissue. A stent was then introduced into the third ventricle via the right lateral ventricle, the fenestration in the septum pellucidum, and the left Monro foramen.

The authors note that fiberscopes are in general more maneuverable than rigid endoscopes and conclude that they are particularly useful for the treatment of this type of hydrocephalus.
Endolymphatic sac tumor demonstrated by intralabyrinthine hemorrhage
Authors: Jagannathan Jay , Butman John A. , Lonser Russell R. , Vortmeyer Alexander O. , Zalewski Christopher K. , Brewer Carmen , Oldfield Edward H. , Kim H. Jeffrey
Published: January 2008

✓ Endolymphatic sac tumors (ELSTs) are locally invasive neoplasms that arise in the posterior petrous bone and are associated with von Hippel–Lindau (VHL) disease. These tumors cause symptoms even when microscopic in size (below the threshold for detectability on imaging studies) and can lead to symptoms such as hearing loss, tinnitus, vertigo, and facial nerve dysfunction. While the mechanisms of audiovestibular dysfunction in patients harboring ELSTs are incompletely understood, they have critical implications for management. The authors present the case of a 33-year-old man with VHL disease and a 10-year history of progressive tinnitus, vertigo, and left-sided hearing loss. Serial T1-weighted magnetic resonance (MR) imaging and computed tomography scans revealed no evidence of tumor, but fluid attenuated inversion recovery (FLAIR) MR imaging sequences obtained after hearing loss demonstrated evidence of left intralabyrinthine hemorrhage. On the basis of progressive disabling audiovestibular dysfunction (tinnitus and vertigo), FLAIR imaging findings, and VHL disease status, the patient underwent surgical exploration of the posterior petrous region, and a small (2-mm) ELST was identified and completely resected. Postoperatively, the patient had improvement of the tinnitus and vertigo. Intralabyrinthine hemorrhage may be an early and the only neuroimaging sign of an ELST in patients with VHL disease and audiovestibular dysfunction. These findings support tumor-associated hemorrhage as a mechanism underlying the audiovestibular dysfunction associated with ELSTs.
Extradural dermoid tumor of the petrous apex
Authors: Ammirati Mario , Delgado Mariel , Slone H. Wayne , Ray-Chaudhury Abhik
Published: January 2008

✓ Dermoid cysts are rare, benign, congenital tumors. Most case series thus far have featured intradural tumors. The authors report on a case of an extradural dermoid tumor of the middle cranial fossa with osseous invasion, successfully removed using a left subtemporal extradural approach. The clinical presentation, histological features, radiological findings, and management of this unique case are described.
Colocalized cellular schwannoma and plexiform neurofibroma in the absence of neurofibromatosis
Authors: Spinner Robert J. , Scheithauer Bernd W. , Perry Arie , Amrami Kimberly K. , Emnett Ryan , Gutmann David H.
Published: January 2008

✓ The authors report on a patient without neurofibromatosis Type 1 or 2 (NF1 or NF2) and without evidence of schwannomatosis, who was found to have an unusual combination of nerve sheath tumors—a large cellular schwannoma and multifascicular involvement of a plexiform neurofibroma arising from the same site within the radial nerve and posterior cord of the infraclavicular brachial plexus. This case broadens the spectrum of combined pathological features of nerve sheath tumors. Genetic studies revealed a combined loss of neurofibromin and merlin in both regions and chromosome arm 22q deletion within the neurofibroma component only. The latter finding supports the suggestion that these were two different clonal neoplasms, and is consistent with a collision tumor pattern.
Identifying vulnerable carotid plaques in vivo using high resolution magnetic resonance imaging–based finite element analysis
Authors: Trivedi Rikin A. , Li Zhi-Yong , U-King-Im Jean , Graves Martin J. , Kirkpatrick Peter J. , Gillard Jonathan H.
Published: January 2008

Object

Individuals with carotid atherosclerosis develop symptoms following rupture of vulnerable plaques. Biomechanical stresses within this plaque may increase vulnerability to rupture. In this report the authors describe the use of in vivo carotid plaque imaging and computational mechanics to document the magnitude and distribution of intrinsic plaque stresses.

Methods

Ten (five symptomatic and five asymptomatic) individuals underwent plaque characterization magnetic resonance (MR) imaging. Plaque geometry and composition were determined by multisequence review. Intrinsic plaque stress profiles were generated from 3D meshes by using finite element computational analysis. Differences in principal (shear) stress between normal and diseased sections of the carotid artery and between symptomatic and asymptomatic plaques were noted.

Results

There was a significant difference in peak principal stress between diseased and nondiseased segments of the artery (mean difference 537.65 kPa, p < 0.05). Symptomatic plaques had higher mean stresses than asymptomatic plaques (627.6 kPa compared with 370.2 kPa, p = 0.05), which were independent of luminal stenosis and plaque composition.

Conclusions

Significant differences in plaque stress exist between plaques from symptomatic individuals and those from asymptomatic individuals. The MR imaging–based computational analysis may therefore be a useful aid to identification of vulnerable plaques in vivo.
Characteristics and distribution of somatosensory evoked potentials in the subthalamic region
Authors: Kitagawa Mayumi , Murata Jun-Ichi , Uesugi Haruo , Hanajima Ritsuko , Ugawa Yoshikazu , Saito Hisatoshi
Published: January 2008

Object

The aim of the present study is to evaluate the topographical distribution of somatosensory evoked potentials (SSEPs) in the subthalamic area, including the zona incerta (ZI). Determination of this distribution may help in the correct placement of deep brain stimulation (DBS) leads.

Methods

Intraoperative SSEPs were recorded from contacts of DBS electrodes at 221 sites in 41 patients: three patients with essential tremor and 38 with Parkinson disease who underwent implantation of DBS electrodes for the relief of severe tremor or parkinsonism.

Results

Two distinct SSEPs were recorded in the subthalamic area. One was a monophasic positive wave with a mean latency of 15.8 ± 0.9 msec, which the authors designated subthalamic P16. Using both cephalic and noncephalic references, subthalamic P16 was only recorded in the ventral part of the ZI (mean 6.6 ± 1. 3 mm posterior to the midcommissure point, 4.8 ± 1.2 mm inferior to the anterior commissure–posterior commissure line, and 9.7 ± 0.6 mm lateral to the midline). When bipolar recordings were made, the traces showed a phase reversal at the caudal part of the ZI. The second potential is a positive–negative SSEP recorded throughout the entire subthalamic area. The mean latencies of the initial positive peak and the major negative peak were 13.6 ± 1.1 msec and 16.4 ± 1.1 msec, respectively. Several small notches were superimposed on the peaks, and their amplitudes were largest at the contact close to the medial lemniscus.

Conclusions

The results indicate that intraoperative SSEPs from DBS electrodes are helpful in refining stereotactic targets in the thalamus and subthalamic areas.
Real-time imaging of convection-enhanced delivery of viruses and virus-sized particles
Authors: Szerlip Nicholas J. , Walbridge Stuart , Yang Linda , Morrison Paul F. , Degen Jeffrey W. , Jarrell S. Taylor , Kouri Joshua , Kerr P. Benjamin , Kotin Robert , Oldfield Edward H. , Lonser Russell R.
Published: January 2008

Object

Despite recent evidence showing that convection-enhanced delivery (CED) of viruses and virus-sized particles to the central nervous system (CNS) is possible, little is known about the factors influencing distribution of these vectors with convection. To better define the delivery of viruses and virus-sized particles in the CNS, and to determine optimal parameters for infusion, the authors coinfused adeno-associated virus ([AAV], 24-nm diameter) and/or feru-moxtran-10 (24 nm) by using CED during real-time magnetic resonance (MR) imaging.

Methods

Sixteen rats underwent intrastriatal convective coinfusion with 4 μl of 35S-AAV capsids (0.5–1.0 × 1014 viral particles/ml) and increasing concentrations (0.1, 0.5, 1, and 5 mg/ml) of a similar sized iron oxide MR imaging agent (ferumoxtran-10). Five nonhuman primates underwent either convective coinfusion of 35S-AAV capsids and 1 mg/ml ferumoxtran-10 (striatum, one animal) or infusion of 1 mg/ml ferumoxtran-10 alone (striatum in two animals; frontal white matter in two). Clinical effects, MR imaging studies, quantitative autoradiography, and histological data were analyzed.

Results

Real-time, T2-weighted MR imaging of ferumoxtran-10 during infusion revealed a clearly defined hypo-intense region of perfusion. Quantitative autoradiography confirmed that MR imaging of ferumoxtran-10 at a concentration of 1 mg/ml accurately tracked viral capsid distribution in the rat and primate brain (the mean difference in volume of distribution [Vd] was 7 and 15% in rats and primates, respectively). The Vd increased linearly with increasing volume of infusion (Vi) (R2 = 0.98). The mean Vd/Vi ratio was 4.1 ± 0.2 (mean ± standard error of the mean) in gray and 2.3 ± 0.1 in white matter (p < 0.01). The distribution of infusate was homogeneous. Postinfusion MR imaging revealed leakback along the cannula track at infusion rates greater than 1.5 μl/minute in primate gray and white matter. No animal had clinical or histological evidence of toxicity.

Conclusions

The CED method can be used to deliver AAV capsids and similar sized particles to the CNS safely and effectively over clinically relevant volumes. Moreover, real-time MR imaging of ferumoxtran-10 during infusion reveals that AAV capsids and similar sized particles have different convective delivery properties than smaller proteins and other compounds.
Neurogenesis in the postnatal human epileptic brain
Authors: González-Martínez Jorge A. , Bingaman William E. , Toms Steven A. , Najm Imad M.
Published: January 2008

Object

The normal adult human telencephalon does not reveal evidence of spontaneous neuronal migration and differentiation despite the robust germinal capacity of the subventricular zone (SVZ) astrocyte ribbon that contains neural stem cells. This might be because it is averse to accepting new neurons into an established neuronal network, probably representing an evolutionary acquisition to prevent the formation of anomalous neuronal circuits. Some forms of epilepsy, such as malformations of cortical development, are thought to be due to abnormal corticogenesis during the embryonic and early postnatal periods. The role of postnatal architectural reorganization and possibly postnatal neurogenesis in some forms of epilepsy in humans remains unknown. In this study the authors used resected specimens of epileptic brain to determine whether neurogenesis could occur in the diseased tissue.

Methods

The authors studied freshly resected brain tissue obtained in 47 patients who underwent neurosurgical procedures and four autopsies. Forty-four samples were harvested in patients who underwent resection for the treatment of pharmacoresistant epilepsy.

Results

Using organotypic brain slice preparations cultured with 5-bromodeoxyuridine (a marker for cell proliferation), immunohistochemistry, and cell trackers, the authors demonstrate the presence of spontaneous cell proliferation, migration, and neuronal differentiation in the adult human telencephalon that starts in the SVZ and progresses to the adjacent white matter and neocortex in human neocortical pathological structures associated with epilepsy. No cell migration or neuronal differentiation was found in the control group.

Conclusions

The presence of spontaneous neurogenesis associated with some forms of human neocortical epilepsy may represent an erroneous and maladaptive mechanism for neuronal circuitry repair, or it may be an intrinsic part of the pathogenic process.
Application of a hydrogel sealant improves watertight closures of duraplasty onlay grafts in a canine craniotomy model
Authors: Preul Mark C. , Campbell Patrick K. , Bichard William D. , Spetzler Robert F.
Published: January 2008

Object

The authors evaluated whether a polyethylene glycol–based hydrogel sealant system improved dural closures with collagen-based duraplasty onlay grafts.

Methods

Dural defects 1.5 cm in diameter were created in 12 canines and repaired with one of two commercially available duraplasty onlay products. In six animals, hydrogel was applied onto the dural onlays, and the other six animals underwent duraplasty only. Before bone flap replacement, watertight closure was assessed. Before the animals were killed, the craniotomy was reopened, adhesions were rated by a neurosurgeon blinded to the treatment groups, and dural integrity was assessed using pressure testing.

Results

The animals that received the hydrogel sealant in addition to the duraplasty withstood intraoperative Valsalva maneuvers up to 20 cm H2O without cerebrospinal fluid (CSF) leakage. The duraplasty-only animals leaked CSF at spontaneous pressures (p = 0.0022). Postoperatively, all six duraplasty-only dogs developed CSF subcutaneous accumulations, compared with only one (16.7%) dog who underwent hydrogel application (p = 0.0152). At the time of harvesting (8 weeks after implantation), duraplasty-only dogs had extensive scarring between the bone flap and the dura mater (median adhesion score 4, range 3–4). The animals receiving hydrogel showed minimal scarring (median adhesion score 0.5, range 0–2). In hydrogel-treated dogs, the mean adhesion score was 82.6% lower than the scores in duraplasty-only animals (p = 0.0043). In animals receiving hydrogel, the mean dural leak pressure was 56.8 ± 2.5 cm H2O compared with 9.8 ± 3.8 cm H2O in duraplasty-only dogs (p = 0.0392). Application of the hydrogel was not associated with neurotoxicity, delayed healing, degenerative changes, or increased dura–cortex adhesions.

Conclusions

The hydrogel sealant applied to collagen-based dural grafts significantly reduced CSF leakage and functioned as an adhesion barrier. Such technology could be an important tool for cranial surgery.
Use of hinge craniotomy for cerebral decompression
Authors: Schmidt John H. , Reyes Bernardo J. , Fischer Roopan , Flaherty Sarah K.
Published: January 2008

✓Decompressive craniectomy to relieve cerebral edema and intracranial hypertension due to traumatic brain injury is a generally accepted practice; however, the procedure remains controversial because of its uncertain effects on outcome, specific complications such as the syndrome of the sinking skin flap, and the need for subsequent cranioplasty. The authors developed a novel craniotomy technique using titanium bone plates in a hinged fashion, which maintains cerebral protection while reducing postoperative complications and eliminating subsequent cranioplasty procedures.

The authors conducted a retrospective review of data obtained in all consecutive patients who had undergone post-traumatic cerebral decompression craniotomy using the hinge technique at a Level I trauma facility between 1990 and 2004.

Twenty-five patients, most of whom were male (88%) and Caucasian (88%) with a mean age of 38.2 ± 16.1 years, underwent the hinge craniotomy. The in-hospital mortality rate was 48%, and good cerebral decompression was achieved. None of the patients required surgery for flap replacement. Long-term follow-up data showed that one patient required subsequent cranioplasty due to infection and one patient presented with cranial deformities. None of the patients presented with bone resorption or sinking flap syndrome.

The hinge technique effectively prevents procedure-related morbidity and the need for subsequent surgical bone replacement otherwise introduced by traditional decompressive craniectomy. A randomized controlled trial is required to substantiate these findings.
Quantitative analysis of the working area and angle of attack for the retrosigmoid, combined petrosal, and transcochlear approaches to the petroclival region
Authors: Siwanuwatn Rungsak , Deshmukh Pushpa , Figueiredo Eberval Gadelha , Crawford Neil R. , Spetzler Robert F. , Preul Mark C.
Published: January 2008

Object

The authors quantitatively assessed the working areas and angles of attack associated with retrosigmoid (RS), combined petrosal (CP), and transcochlear (TC) craniotomies.

Methods

Four silicone-injected cadaveric heads were bilaterally dissected using three approaches progressing from the least to the most extensive. Working areas were determined using the Optotrak 3020 system on the upper and middle thirds of the petroclivus and brainstem. Angles of attack were studied using the Elekta SurgiScope at the Dorello canal and the origin of the anterior inferior cerebellar artery (AICA).

The TC approach provided significantly greater (p < 0.001) working areas at the petroclivus (755.6 ± 130.1 mm2) and brainstem (399.3 ± 68.2 mm2) than the CP (354.1 ± 60.3 and 289.7 ± 69.9 mm2) and RS approaches (292.4 ± 59.9, 177.2 ± 54.2 mm2, respectively). The brainstem working area associated with the CP approach was significantly larger (p < 0.001) than that associated with the RS route. There was no difference in the petroclival working area comparing the CP and RS approaches (p = 0.149). The horizontal and vertical angles of attack achieved using the TC approach were wider than those of the CP and RS at the Dorello canal and the origin of the AICA (p < 0.001).

Conclusions

The CP approach offers a more extensive working area than the RS for lesions involving the anterolateral surface of the brainstem, but not for petroclival lesions. The TC approach provides the widest corridor, improving the working area and angle of attack to both areas, but hearing must be sacrificed and the facial nerve is at risk.
Reorganization of the cortical control of movement due to radiation necrosis
Authors: Hou Bob L. , Holodny Andrei I. , Cooperman Nathan , Gutin Philip H.
Published: January 2008

✓The authors report a case of reorganization of the cortical control of movement caused by radiation necrosis based on an analysis of functional magnetic resonance (fMR) imaging data acquired during a finger-tapping paradigm. Radiation necrosis in this patient extended from the parietal lobe anteriorly to the primary motor cortex (PMC), and fMR imaging demonstrated an increase in activation in the ipsilateral supplementary motor area. This is similar to the consequences of invasion by glial tumors into the PMC.
Bromocriptine treatment of invasive giant prolactinomas involving the cavernous sinus: results of a long-term follow up
Authors: Wu Zhe Bao , Yu Chun Jiang , Su Zhi Peng , Zhuge Qi Chuan , Wu Jin Sen , Zheng Wei Ming
Published: January 2008

Object

The aim of this study was to observe long-term clinical outcomes in a group of patients treated with bromocriptine for invasive giant prolactinomas involving the cavernous sinus.

Methods

Data from 20 patients with invasive giant prolactinomas at the authors’ institutions between July 1997 and June 2004 were retrospectively reviewed. The criteria to qualify for study participation included: 1) tumor diameter greater than 4 cm, invading the cavernous sinus to an extent corresponding to Grade III or IV in the classification scheme of Knosp and colleagues; 2) serum prolactin (PRL) level greater than 200 ng/ml; and 3) clinical signs of hyperprolactinemia and mass effect. Among the 20 patients who met the criteria, six had undergone unsuccessful transcranial or transsphenoidal microsurgery prior to bromocriptine treatment and 14 patients received bromocriptine as the primary treatment. Eleven of the 20 patients underwent adjuvant radiotherapy.

After a mean follow-up period of 37.3 months, the clinical symptoms in all patients improved by different degrees. Tumor volume on magnetic resonance images was decreased by a mean of 93.3%. In 11 patients, the tumor had almost completely disappeared; in the other nine patients, residual tumor invaded the cavernous sinus. Visual symptoms improved in 13 of the patients who had presented with visual loss. Eight patients had normal PRL levels. The postoperative PRL level was more than 200 ng/ml in seven patients. During the course of drug administration, cerebrospinal fluid leakage occurred in one patient, who subsequently underwent transsphenoidal surgery. No case of apoplexy occurred during bromocriptine treatment.

Conclusions

Dopamine agonist medications are effective as a first-line therapy for invasive giant prolactinomas, because they can significantly shrink tumor volume and control the PRL level. Tumor mass vanishes in some patients after bromocriptine treatment; in other patients with localized residual tumor, stereotactic radiosurgery is a viable option so that unnecessary surgery can be avoided. The application of radiotherapy does not reliably shrink tumor volume.
Development of a histological pseudocapsule and its use as a surgical capsule in the excision of pituitary tumors
Authors: Oldfield Edward H. , Vortmeyer Alexander O.
Published: January 2008

Object

The presence of a histological pseudocapsule around pituitary tumors was noted in the early 1900s. Since that time there has been no emphasis on the sequence of the stages of its development or on the relationship between these stages and the capacity to identify very small pituitary tumors at surgery in patients in whom preoperative imaging has been nondiagnostic. In addition, limited emphasis has been given to the pseudocapsule’s use for selective and complete resection of pituitary adenomas.

Methods

The development of the pseudocapsule was examined by performing histological analysis of portions of pituitary glands removed during 805 operations for Cushing disease.

Twenty-five adenomas, each measuring between 0.25 and 4 mm in maximum diameter, were detected in the excised specimens; 17 were adenocorticotropic hormone–positive adenomas and eight were incidental tumors (four prolactin-secreting and four nonsecreting lesions). In 16 tumors the size of the adenoma could be established. The distribution of tumor size in relation to the presence of a histological pseudocapsule indicates a transition from the absence of a reticulin capsule (tumor diameter ≤ 1 mm) through the initial compression of surrounding tissue (tumor diameter 1–2 mm) to the presence of a multilayered reticulin capsule observed when adenomas become larger (tumor diameter 2–3 mm).

Conclusions

The absence of a reticulin capsule in cases of very small tumors may contribute to limited localization of these lesions during surgical exploration of the pituitary gland. In this article the authors describe surgical techniques in which the histological pseudocapsule is used as a surgical capsule during pituitary surgery. In their experience, recognition of this surgical capsule and its use at surgery has contributed to the identification of microadenomas buried in the pituitary gland, aided the recognition of subtle invasion of the pituitary capsule and contiguous dura mater, and enhanced the consistency of complete tumor excision with small and large tumors.