bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medical management of Cushing disease
Authors: Gross Bradley A. , Mindea Stefan A. , Pick Anthony J. , Chandler James P. , Batjer H. Hunt 
Published: January 2008

✓Although transsphenoidal excision of the adrenocorticotropic hormone (ACTH)–producing neoplasm is often the treatment of choice in patients with Cushing disease, medical management is itself a useful preoperative temporizing measure, an option for long-term management in nonsurgical candidates, and an option for patients in whom surgery and/or radiotherapy have failed. Three pathophysiologically based approaches exist in the research literature—neuro-modulation to limit ACTH levels, adrenal enzyme inhibition, and glucocorticoid receptor antagonism. Unfortunately, the neuromodulatory approach involving agents such as bromocriptine, cyproheptadine, octreotide, and valproate has yielded only suboptimal results. Glucocorticoid receptor antagonism remains in its infancy but may overall be limited by side effects and a resultant increase in ACTH and cortisol levels. Adrenal enzyme inhibitors, however, offer substantial future promise in the management of Cushing disease but are limited by the potential need to use them indefinitely and by dose-tolerance effects.
Although etomidate is a potential intravenous alternative for acute cortisol level control, ketoconazole has shown efficacy in the long-term treatment of patients with the disease. Metyrapone and/or aminoglutethimide can be added to ketoconazole if additional control is needed. If success is still not achieved, the potent adrenolytic agent often used for adrenocortical carcinomas, mitotane, is another alternative.
Relation among aneurysm size, amount of subarachnoid blood, and clinical outcome
Authors: Salary Montell , Quigley Matthew R. , Wilberger Jack E. 
Published: January 2008

Object
The authors of recent reports have suggested that smaller aneurysms are associated with more extensive sub-arachnoid hemorrhage (SAH), which could potentially presage poor outcome in patients harboring these lesions. The authors reviewed their clinical experience to determine if this theory has a basis in truth.

Methods
The authors undertook a retrospective review of a consecutive series of patients with aneurysmal SAH. Computed tomography scans and angiograms were studied to establish SAH scores and aneurysm size.

Results
One hundred thirty-three patients were treated during a 2-year period (January 2003–December 2004). There were 101 female and 32 male patients whose mean age was 56.7 years. The location distribution of aneurysms that bled was as follows: anterior communicating artery (56 cases), posterior communicating artery (34 cases), middle cerebral artery (21 cases), posterior circulation (16 cases), and paraclinoid region (six cases). The mean aneurysm size was 6.2 mm (range 2–26 mm). The mean SAH score was 18.3 (not normally distributed, p < 0.01, D'Agostino–Pearson test). One hundred three patients underwent surgical exploration and placement of an aneurysm clip, 21 underwent deployment of a coil, and two underwent both therapies; seven patients died prior to intervention.
No correlation was found between aneurysm size and SAH score (rS = −0.023, p = 0.8) or between small aneurysm size and poor Glasgow Outcome Scale score (p = 0.13). In fact, the trend was the opposite. The SAH score did, however, correspond strongly with the admission Hunt and Hess grade (p < 0.0001), indicating the strong correlation between grade and volume of intracranial blood. Outcome was best explained in the multivariate analysis by the following factors: admission Hunt and Hess grade, age, and clinical vasospasm (p < 0.0001) with the proportion of cases correctly classified as 79.7%.

Conclusions
Evaluation of the results in the present clinical series suggests that there is no relation between aneurysm size and volume of subarachnoid blood. The volume of cisternal blood correlates with Hunt and Hess grade but is not an independent determinant of outcome. Outcome is related to the following triad of well-established clinical factors: Hunt and Hess grade, age, and clinical vasospasm.
Subthalamic nucleus deep brain stimulation for severe idiopathic dystonia: impact on severity, neuropsychological status, and quality of life
Authors: Kleiner-Fisman Galit , Lin Liang Grace S. , Moberg Paul J. , Ruocco Anthony C. , Hurtig Howard I. , Baltuch Gordon H. , Jaggi Jurg L. , Stern Matthew B. 
Published: January 2008

Object
Medically refractory dystonia has recently been treated using deep brain stimulation (DBS) targeting the globus pallidus internus (GPI). Outcomes have varied depending on the features of the dystonia. There has been limited literature regarding outcomes for refractory dystonia following DBS of the subthalamic nucleus (STN).

Methods
Four patients with medically refractory, predominantly cervical dystonia underwent STN DBS. Intraoperative assessments with the patients in a state of general anesthesia were performed to determine the extent of fixed deformities that might predict outcome. Patients were rated using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) preoperatively and 3 and 12 months following surgery by a rater blinded to the study. Mean changes and standard errors of the mean in scores were calculated for each subscore of the two scales. Scores were also analyzed using analysis of variance and probability values were generated. Neuropsychological assessments and quality of life ratings using the 36-Item Short Form Health Survey (SF-36) were evaluated longitudinally.

Results
Significant improvements were seen in motor (p = 0.04), disability (p = 0.02), and total TWSTRS scores (p = 0.03). Better outcomes were seen in those patients who did not have fixed deformities. There was marked improvement in the mental component score of the SF-36. Neuropsychological function was not definitively impacted as a result of the surgery.

Conclusions
Deep brain stimulation of the STN is a novel target for dystonia and may be an alternative to GPI DBS. Further studies need to be performed to confirm these conclusions and to determine optimal candidates and stimulation parameters.
Contralateral conjugate eye deviation during deep brain stimulation of the subthalamic nucleus
Authors: Shields Donald C. , Gorgulho Alessandra , Behnke Eric , Malkasian Dennis , Desalles Antonio A. F. 
Published: January 2008

Object
Deep brain stimulation of the subthalamic nucleus (STN) in patients with Parkinson disease is often very effective for treatment of debilitating motor symptoms. Nevertheless, the small size of the STN and its proximity to axonal projections results in multiple side effects during high-frequency stimulation. Contralateral eye deviation is produced in a small percentage of patients, but the precise mechanism of this side effect is at present poorly understood.

Methods
Contralateral eye deviation was produced by high-frequency stimulation of 22 contact sites in nine patients undergoing deep brain stimulation of the STN. The precise locations of these contacts were calculated and compiled in order to locate the stimulated structure responsible for eye deviation.

Results
The mean x, y, and z coordinates associated with contralateral eye deviation were found to be 11.57, 2.03, and 3.83 mm lateral, posterior, and inferior to the anterior commissure–posterior commissure midpoint, respectively. The point described by these coordinates is located within the lateral anterosuperior border of the STN.

Conclusions
Given that stimulation of frontal eye field cortical regions produces similar contralateral conjugate eye deviation, these results are best explained by electrical current spread to nearby frontal eye field axons coursing lateral to the STN within the internal capsule. Thus, placement of the implanted electrode in a more medial, posterior, and inferior position may bring resolution of these symptoms by reducing the amount of current spread to internal capsule axons.
Effect of delayed cerebral vasospasm on cerebrovascular endothelin A receptor expression and function
Authors: Vatter Hartmut , Konczalla Juergen , Weidauer Stefan , Preibisch Christine , Zimmermann Michael , Raabe Andreas , Seifert Volker 
Published: January 2008

Object
The key role in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH) is increasingly assigned to endothelin (ET)-1. Constriction of the cerebrovasculature by ET-1 is mainly mediated by the ETA receptor but is putatively altered during the development of cerebral vasospasm. Therefore, the aim in the present study was to characterize these alterations, with the emphasis on the ETA receptor.

Methods
Cerebral vasospasm was induced using the rat double-hemorrhage model and proven by perfusion weighted magnetic resonance imaging. Rats were killed on Day 5 after SAH, and immunohistochemical staining for ETA receptors was performed. The isometric force of basilar artery ring segments with (E+, control group) and without (E−, SAH group) endothelial function was measured. Concentration effect curves (CECs) for ET-1 were constructed by cumulative application in the absence and presence of the selective ETA receptor antagonist clazosentan (10−8 or 10−7 M).

Results
The CEC for E+ segments was significantly shifted to the left after SAH by a factor of 3.7, whereas maximum contraction was unchanged. In E− segments, the CECs were not shifted during cerebral vasospasm but the maximum contraction was significantly enhanced. The inhibitory potency of clazosentan yielded a pA2 value of 8.6 ± 0.2. Immunohistochemical staining of the smooth-muscle layer showed no significant increase of ETA receptor expression, but positive staining occurred in the endothelial space after SAH.

Conclusions
The present data indicate an enhanced contractile effect of the smooth-muscle ETA receptors in cases of cerebral vasospasm. The inhibitory potency of clazosentan on this contraction is increased. Furthermore, some evidence for an ETA receptor and an endothelium-dependent vasoactive effect after SAH is provided.
Selective differentiation of central nervous system–derived stem cells in response to cues from specific regions of the developing brain
Authors: Vorasubin Bonnie , Weedin John , Saljooque Farid , Wilkes Nathan , U Hoi Sang 
Published: January 2008

Object
Each region of the brain is distinguished by specific and distinct markers and functions. The authors hypothesized that each region possesses unique trophic properties that dictate and maintain its development. To test this hypothesis, they isolated central nervous system (CNS) stem cells from fetal rodents, and these rat CNS-derived stem cells (RSCs) were placed in coculture with primary cultures of the developing neonatal hippocampus and hypothalamus to determine whether region-specific primary cells would direct the differentiation of stem cells in a region-specific manner.

Methods
Primary cultures were first established from the neonatal (3–7 days postnatal) hippocampus and hypothalamus. Rodent CNS stem cells, which had been genetically engineered to express green fluorescent protein, were then placed in coculture with the primary CNS cells. The expression of region-specific markers in the RSCs was then evaluated after 2 weeks using immunocytochemistry. Data from previous studies have indicated that primary adult cells lack a differentiation-inducing capacity.

Results
When placed in coculture with primary CNS cells, RSCs began to express both neuronal (MAP2) and glial (glial fibrillary acidic protein) markers. Those that were placed in coculture with hippocampal cells expressed region-specific markers such as γ-aminobutyric acid, whereas those placed in coculture with hypothalamic cells expressed growth hormone–releasing hormone primarily in the hypothalamus.

Conclusions
Pluripotential RSCs were induced to express region-specific phenotypes on coculture with primary cells derived from the developing hippocampus and hypothalamus. The differentiation of RSCs into specific lineages on exposure to specific cell types is likely modulated through direct cell–cell contact. Secreted factors from the primary neural cells may also play a role in this induction. Such a differentiation influence is also likely age dependent.
Anatomy of the falcine venous plexus
Authors: Tubbs R. Shane , Loukas Marios , Louis Robert G. , Shoja Mohammadali M. , Acakpo-Satchivi Leslie , Blount Jeffrey P. , Salter E. George , Oakes W. Jerry , Wellons John C. 
Published: January 2008

Object
The superior and inferior sagittal sinuses have been well studied. Interestingly, other venous structures within the falx cerebri have received scant attention in the medical literature. The present study was performed to elucidate the presence and anatomy of these midline structures.

Methods
The authors examined 27 adult latex- or ink-injected cadaveric specimens to observe the morphological features of the sinuses within the falx cerebri (excluding the inferior and superior sagittal sinuses).

Results
All specimens were found to have an extensive network of small tributaries within the falx cerebri that were primarily concentrated in its posterior one third. In this posterior segment, these structures were usually more pronounced in the inferior two thirds. The portion of the falx cerebri not containing significant falcine venous sinus was termed a “safe area.” These vascular channels ranged in size from 0.5 mm to 1.1 cm (mean 0.6 mm); 100% of these vessels communicated with the inferior sagittal sinus. Classification of the structures was then performed based on communication of the falcine venous sinus with the superior sagittal sinus. Type I falcine sinuses had no communication with the superior sagittal sinus, Type II falcine sinuses had limited communication with the superior sagittal sinus, and Type III falcine sinuses had significant communication with the superior sagittal sinus. Seventeen (63%) of 27 specimens communicated with the superior sagittal sinus (Types II and III). Further subdivision revealed 10 Type I, seven Type II, and 10 Type III falcine venous plexuses.

Conclusions
There are other venous sinuses in the falx cerebri in addition to the superior and inferior sagittal sinuses. Neurosurgical procedures that necessitate incising or puncturing the falx cerebri can be done more safely via a described safe area. Given that the majority of specimens in the authors' study were found to have a plexiform venous morphology within the falx cerebri, they propose that these channels be referred to as the falcine venous plexus and not sinus. The falcine venous plexus should be taken into consideration by the neurosurgeon.
Neuromodulation of the cingulum for neuropathic pain after spinal cord injury
Authors: Spooner John , Yu Hong , Kao Chris , Sillay Karl , Konrad Peter 
Published: January 2008

✓The authors present a case in which high-frequency electrical stimulation of the cingulum using standard deep brain stimulation (DBS) technology resulted in pain relief similar to that achieved with cingulotomy and superior to that achieved with periventricular gray matter (PVG) stimulation.
This patient had a complete spinal cord injury at the C-4 level and suffered from medically refractory neuropathic pain. He underwent placement of bilateral cingulum and unilateral PVG DBS electrodes and a 1-week blinded stimulation trial prior to permanent implantation of a pulse generator. During the stimulation trial, the patient's pain level was assessed using a visual analog scale, and pain medication usage was recorded. During this period the patient was blinded to stimulation parameters. Stimulation of the cingulum provided better pain control than PVG stimulation or medication alone.
The authors believe that cingulum stimulation can benefit patients with severe neuropathic pain that is refractory to other treatments. Advantages over cingulotomy include reversibility and the ability to adjust stimulation parameters for optimum efficacy.
Usefulness of 123I-iomazenil single-photon emission computed tomography in discriminating between mesial and lateral temporal lobe epilepsy in patients in whom magnetic resonance imaging demonstrates normal findings
Authors: Umeoka Shuichi , Matsuda Kazumi , Baba Koichi , Usui Naotaka , Tottori Takayasu , Terada Kiyohito , Usui Keiko , Nakamura Fumihiro , Inoue Yushi , Fujiwara Tateki , Mihara Tadahiro 
Published: January 2008

Object
To provide greater accuracy in determining the epileptogenic zone during preoperative evaluation, the authors retrospectively examined 123I-iomazenil single-photon emission computed tomography (IMZ SPECT) studies obtained in patients with temporal lobe epilepsy (TLE) in whom there was no evidence of an abnormality on magnetic resonance (MR) images.

Methods
Twelve patients, seven with mesial TLE (MTLE) and five with lateral TLE (LTLE), satisfied the criteria for inclusion in the study. The IMZ SPECT findings in these patients were reviewed retrospectively, and a comparison was made between findings in patients with MTLE and those in patients with LTLE.

Results
The IMZ SPECT studies demonstrated decreased IMZ uptake in the ipsilateral mesial temporal region and the anterobasal temporal lobe in all patients who had MTLE on only one side. On the other hand, IMZ SPECT examinations revealed low IMZ uptake in the ipsilateral lateral temporal lobe in four of five patients with LTLE in whom abnormal findings were restricted to the lateral neocortex. In the remaining patient with LTLE, abnormally low IMZ uptake was found in both mesial and lateral temporal lobes, although pure LTLE was diagnosed by an invasive electroencephalographic evaluation; this patient's habitual seizures continued even after temporal lobectomy, although his mesial structures were spared.

Conclusions
The authors report characteristics of IMZ SPECT findings that differed between patients with MTLE and those with LTLE. The IMZ SPECT examinations proved useful for preoperative evaluation and, to a certain extent, for discrimination between MTLE and LTLE in cases in which MR imaging demonstrated normal findings. The results of this study suggest that IMZ SPECT findings may reflect localization of the epileptogenic zone.
Selection of the donor nerve for end-to-side neurorrhaphy
Authors: Papalia Igor , Cardaci Aurelio , d'Alcontres Francesco Stagno , Lee Jennifer M. , Tos Pierluigi , Geuna Stefano 
Published: January 2008

Object
The authors of other studies have reported that the selection of an agonistic donor nerve is required for recovering voluntary motor control after end-to-side nerve repair. In this experimental investigation, the authors' goal was to verify this assumption by performing end-to-side neurorrhaphy of the rat median nerve on its antagonistic radial nerve.

Methods
The left median nerve in 10 adult female rats was repaired by end-to-side neurorrhaphy after epineuriotomy on the radial nerve at the middle of the brachium. The time course of median nerve functional recovery was then assessed using the grasping test until postoperative Week 30. Before removing the nerve, the surgical site was carefully explored to exclude contamination by the proximal nerve stump, and the functional anatomy of median and radial nerves was assessed by electrical stimulation. Repaired nerves were then processed for resin embedding, and semithin sections were obtained for nerve fiber histomorphometry by using the dissector method.

Results
Repaired median nerves were repopulated by nerve fibers regenerating from the radial donor nerve as previously shown. Moreover, voluntary motor control of the flexor muscles innervated by the median nerve was progressively recovered beginning in postoperative Week 10 and reaching 42% of normal by Week 30.

Conclusions
Contrary to previously reported data, recovery of voluntary motor function after end-to-side nerve repair can also be expected when an antagonistic nerve is used as a donor nerve.
Electrocorticography discharge patterns in patients with a cavernous hemangioma and pharmacoresistent epilepsy
Authors: Ferrier Cyrille H. , Aronica Eleonora , Leijten Frans S. S. , Spliet Wim G. M. , Boer Karin , Van Rijen Peter C. , Van Huffelen Alexander C. 
Published: January 2008

Object
Neurodevelopmental lesions (NDLs) such as glioneuronal tumors and cortical dysplasia produce characteristic electrocorticography (ECoG) discharge patterns. Because cavernomas, another congenital abnormality, are also associated with pharmacoresistant epilepsy, the authors wondered whether they exhibit discharge patterns similar to those occurring in NDLs.

Methods
Intraoperative ECoG recordings from 19 patients with cavernomas and 54 with NDLs were reviewed for continuous spikes, bursts, or recruiting discharges and to determine whether these patterns were spatially coincident with the lesion. Relative densities of microglia and the intensity of Fe3+ staining in surgical samples were evaluated. Seizure outcome was assessed 1 year after surgery.

Results
The mean ages at seizure onset and surgery were higher in patients in the cavernoma group than in the NDL group (22.5 and 36.4 years compared with 10.0 and 25.2 years, respectively). Neocortical discharge patterns occurred equally in patients with either cavernomas (53%) or NDLs (41%). In the mesiotemporal area coincident bursts occurred more often in patients with cavernomas than patients with NDLs (55% compared with 10%, respectively). Coincident continuous spiking was associated with a longer duration of epilepsy in patients with cavernomas (23.5 years compared with 11.4 years for those without coincident continuous spiking) and with a lower age at seizure onset in those with NDLs (4.1 years compared with 11.8 years for those without coincident continuous spiking). In the cavernoma group the absence of coincident bursts was associated with high microglia density. There were no associations between the intensity of Fe3+ staining and discharge patterns, although the discharge patterns were associated with a worse outcome in patients with NDLs.

Conclusions
In patients with NDLs, continuous spiking patterns may be markers of a widespread epileptogenic zone due to an early insult to the developing brain; in patients with cavernomas, such patterns may indicate secondary epileptogenesis. Microglia may inhibit discharge patterns in patients with cavernomas.