bluuebunny/crossref_metadata_2025 huggingface dataset:
Diurnal and seasonal variations in the onset of primary intracerebral hemorrhage in individuals living in Izumo City, Japan
Authors: Inagawa Tetsuji
Published: May 2009

Object. Little is known about the temporal patterns of primary intracerebral hemorrhage (ICH) among the general population. The aim of this study was to examine diurnal and seasonal variations in the onset of ICH in a community-based series.

Methods. The study population consisted of 350 patients who presented with primary ICH for the first time and were treated between 1991 and 1998 in Izumo City, Japan. Among the entire patient population, the onset of hemorrhage was rarely observed during the night and a peak was observed in the late afternoon. In men 69 years of age or younger, the onset of ICH exhibited a bimodal distribution, with an initial high peak between 8:00 and 10:00 a.m. and a second, lower peak between 6:00 and 8:00 p.m. In contrast, in men 70 years of age or older and in women regardless of age, only a single evening peak, between approximately 6:00 and 10:00 p.m., was found, and no morning peak was observed. For the entire patient population (for both sexes), and for men alone, seasonal variations—a peak in winter and a trough in summer—were significant for all age groups combined. This factor was significant for patients 69 years of age or younger, during the daytime hours (8:00 a.m.–8:00 p.m.), and for patients with untreated hypertension; however, it was not significant for patients 70 years of age or older, during nighttime hours (10:00 p.m.–8:00 a.m.), or for treated hypertensive and normotensive patients. In women, no significant seasonal patterns were found, regardless of patient age, time of day at onset of ICH, or the presence of risk factors. Seasonal variations were statistically significant for patients with hematomas larger than 5 ml, but not for those with hematomas 5 ml or smaller.

Conclusions. Temporal distributions in the onset of ICH seem to be influenced by patient sex and age. The seasonal patterns of ICH occurrence may result mainly from changes that occur during the daytime, and may also be modified by the presence of untreated hypertension and by the volume of the hematoma.
Endonasal transsphenoidal approach to treat pituitary adenomas and other sellar lesions: an assessment of efficacy, safety, and patient impressions of the surgery
Authors: Zada Gabriel , Kelly Daniel F. , Cohan Pejman , Wang Christina , Swerdloff Ronald
Published: May 2009

Object. The direct endonasal approach performed with the aid of an operating microscope for removal of pituitary tumors has the potential advantage over the traditional sublabial route of minimizing postoperative rhinological complications, yet maintaining a high degree of efficacy and safety. To assess the effectiveness of this procedure, tumor remission rates and surgical complications were documented, and patients' postoperative complaints were recorded using a questionnaire.

Methods. One hundred consecutive patients underwent 109 endonasal operations for tumor removal. At a median follow-up period of 16 months (range 3–45 months), surgical remission rates were as follows: in 40 patients with endocrine-inactive macroadenomas, 95% for noninvasive and 40% for invasive tumors; in the 20 patients with prolactinomas, 75% for prolactinomas with an initial prolactin (PRL) level lower than 200 ng/ml, 33% for those with a PRL level between 200 and 600 ng/ml, and 0% for those with a PRL level higher than 1400 ng/ml; in the 15 patients with Cushing disease, 73% for microadenomas and 25% for macroadenomas; in the 10 patients with acromegaly, 75% for microadenomas and 50% for macroadenomas; in the five patients with Rathke cleft cysts, 80%; and in the five patients with craniopharyngiomas, 40%. There were seven major surgical complications and no operative deaths. Among the 78 patients who completed questionnaires (response rate 89%), the most common complaints concerned nasal packing (39%), removal of packing (36%), and mouth breathing (35%). At 3 months or longer after surgery, patients quantified sinonasal problems as follows: for facial pain, no problem in 83% and severe difficulty in 4%; for nasal congestion, no problem in 74%, and severe difficulty in 3%; for decreased nasal airflow, no problem in 77% and severe difficulty in 4%; for decreased sense of smell, no problem in 73% and severe difficulty in 4%; and for upper-lip numbness, no problem in 87% and severe difficulty in 1%. Twelve (86%) of 14 patients who had undergone sublabial surgery previously preferred the endonasal approach in terms of pain and ease of recovery.

Conclusions. The direct endonasal route for pituitary tumor removal has efficacy and complication rates comparable to those of the sublabial route. Patients generally recover rapidly from this minimally invasive procedure and have no or minimal sinonasal complaints. For patients requiring a repeated operation, the endonasal route appears to be less painful and easier to recover from than the sublabial route. Given the minimal nasal mucosal dissection required and the frequent patient complaints related to nasal packing, use of packing is no longer used for this procedure.
Surgical handling characteristics of an ethylene vinyl alcohol copolymer compared with N-butyl cyanoacrylate used for embolization of vessels in an arteriovenous malformation resection model in swine
Authors: Akin Eric D. , Perkins Eddie , Ross Ian B.
Published: May 2009

Object. There have been significant improvements in neurovascular technology and implants over the past decade. One such material, N-butyl cyanoacrylate (NBCA), is now commercially available for cerebral arteriovenous malformation (AVM) embolization in the US. An ethylene vinyl alcohol copolymer preparation, Onyx, which is currently being evaluated, is approved for use outside North America. Although reports indicate that Onyx may be superior to NBCA from an endovascular perspective, little information exists about its surgical handling characteristics. The purpose of this study was to compare the surgical handling characteristics of Onyx-treated vessels with those of NBCA-embolized vessels in an AVM resection model.

Methods. Fourteen pigs (two groups of seven) were anesthetized. A femoral artery was cannulated, followed by selective catheterization of the ascending pharyngeal arteries. Nidal rete mirabile (RM) embolizations were performed using either 6% Onyx or 20% NBCA. After angiographically confirmed obliteration of flow in the right RM, microsurgical resection of this structure was performed. Surgical handling characteristics of the embolized RM were rated on a scale of 1 to 5 and blood loss was recorded. Different surgeons performed the embolizations and resections. The surgeon who performed resections was blinded to the embolization agent used, and the data analysis was also performed in a blinded fashion. The surgical handling scores were superior (p < 0.05) in the Onyx-treated group. Although there was also less blood loss in this group, the difference was not significant. Subjectively, the surgeon who performed the resections believed that Onyx was softer and handled better than NBCA.

Conclusions. Onyx, which may offer endovascular advantages, also seems to provide benefits for the surgeon.
Cytotoxicity in glioma cells due to interleukin-12 and interleukin-18—stimulated macrophages mediated by interferon-γ regulated by nitric oxide
Authors: Kito Tomohiro , Kuroda Etsushi , Yokota Akira , Yamashita Uki
Published: May 2009

Object. Interleukin (IL)-12 and IL-18 synergistically mediate antitumor responses through the production of interferon-γ (IFNγ) by T and natural killer (NK) cells. Recently, it has been reported that macrophages stimulated with these cytokines also produce IFNγ, which led the authors to investigate the antiglioma activity of macrophages stimulated by the combination of these cytokines in vitro.

Methods. Dish-adherent peritoneal exudate cells, which had been elicited in thioglycollate broth as a source of macrophages, were used in the experiment. The murine glioma cell lines VM-glioma and 203G were labeled with [3H]thymidine for a cytotoxicity assay of macrophages. In response to the combined stimulation by IL-12 and IL-18, macrophages expressed potent cytotoxic activity against glioma cells in association with increasing production of IFNγ and nitric oxide (NO). Inhibitors of NO abrogated the cytotoxic activity of the macrophages, which had been induced by IL-12 and IL-18, despite the increase in IFNγ production. Neutralization of IFNγ or use of macrophages obtained from IFNγ gene-knockout mice markedly reduced not only cytotoxic activity, but also NO production. Depletion of T and NK cells from the macrophage population, which was achieved using antibody plus complement treatment, slightly reduced macrophage activities, suggesting that these are the main effector cells, although T and NK cells may partially participate in this cytotoxicity.

Conclusions. Macrophages stimulated with IL-12 and IL-18 produced IFNγ and NO, which in turn mediated the antiglioma response. Therefore, macrophages as well as T and NK cells play an important role in antitumor responses stimulated by IL-12 and IL-18.
Distinctions between pituicytoma and ordinary pilocytic astrocytoma
Authors: Katsuta Toshiro , Inoue Tooru , Nakagaki Hiroyuki , Takeshita Morishige , Morimoto Ken , Iwaki Toru
Published: May 2009

✓ The authors present a rare case of pituicytoma. A dynamic magnetic resonance study performed after Gd injection revealed a markedly, homogeneously enhanced, early-phase pituitary lesion in a 32-year-old woman with a 1-year history of amenorrhea. The tumor bled easily during transsphenoidal resection. The lesion consisted of plump spindle cells and lacked Rosenthal fibers and granular bodies, and thus was different from ordinary pilocytic astrocytoma or any other form of this tumor. Although pituicytoma is often confused with pilocytic astrocytoma when it appears in the sellar region, these two kinds of gliomas should be distinguished on the basis of histological differences.
Continued growth of and increased symptoms from a thrombosed giant aneurysm of the vertebral artery after complete endovascular occlusion and trapping: the role of vasa vasorum
Authors: Iihara Koji , Murao Kenichi , Sakai Nobuyuki , Soeda Akio , Ishibashi-Ueda Hatsue , Yutani Chikao , Yamada Naoaki , Nagata Izumi
Published: May 2009

✓ A 58-year-old woman harboring a partially thrombosed giant aneurysm of the vertebral artery (VA) presented with lower cranial nerve palsies and cerebellar ataxia. The authors initially attempted to reduce the mass effect by obliterating the lumen of the aneurysm as well as by trapping of the parent artery with coils. Although there was no angiographically demonstrated evidence of filling, the aneurysm continued to enlarge. Magnetic resonance imaging revealed a marked enhancement around the packed coils close to the neck of the aneurysm. Aneurysmectomy and removal of the coils were performed and resulted in an almost complete cure of the patient's symptoms. Interestingly, at the time of resection, a marked development of vasa vasorum on the occluded VA and the neck of the aneurysm was noted. When the occluded VA was cut, there was blood oozing through the coils packed within its lumen on the side where the aneurysm lay. Histological examination showed the presence of inflammatory cells and neovascularization of a partially organized thrombus around the packed coils in both the aneurysm and occluded VA. The proliferation of vasa vasorum was also recognized histologically. This unique case provides insight into the growth mechanisms of a partially thrombosed giant aneurysm after an apparently complete occlusion by endovascular treatment, especially the role of vaso vasorum on the occluded parent artery in the dynamic process of neovascularization in the incomplete organization of thrombus around the packed coils.
Significance of a small bulge on the basilar artery in patients with perimesencephalic nonaneurysmal subarachnoid hemorrhage
Authors: Matsumaru Yuji , Yanaka Kiyoyuki , Muroi Ai , Sato Hiroaki , Kamezaki Takao , Nose Tadao
Published: May 2009

✓ Perimesencephalic nonaneurysmal subarachnoid hemorrhage (SAH) is a distinct type of hemorrhage with a characteristic bleeding pattern and an excellent clinical outcome. The cause of this benign form of SAH remains unknown. The authors report on two cases of perimesencephalic nonaneurysmal SAH in which a small bulge on the basilar artery (BA) was demonstrated on three-dimensional rotational angiography studies. Based on data from these cases, one may infer that the lesion on the BA is responsible for the SAH. The possible pathogenesis is discussed.
Pathophysiology of headache associated with cough in patients with Chiari I malformation
Authors: Sansur Charles A. , Heiss John D. , DeVroom Hetty L. , Eskioglu Eric , Ennis Robert , Oldfield Edward H.
Published: May 2009

Object. The aim of this study was to evaluate the pathophysiology underlying headache associated with cough in patients with Chiari I tonsillar abnormality. The authors hypothesized that peak intrathecal pressure during coughing is higher in patients with headache aggravated by cough than in patients without or in healthy volunteers. In addition, the authors evaluated the use of intrathecal pressure during cough as a means of assessing obstruction to the free flow of cerebrospinal fluid (CSF) at the craniocervical junction.

Methods. Twenty-six adult patients with Chiari I malformation and syringomyelia, four adult patients with Chiari I malformation without syringomyelia, and 15 healthy volunteers were prospectively studied. Testing before surgery included the following: 1) clinical evaluation for the presence of headache associated with cough; and 2) evaluation of lumbar subarachnoid pressure at rest, during three to five coughs, while performing the Valsalva maneuver, during jugular compression, and after removal of CSF. Patients underwent suboccipital craniectomy, C-1 laminectomy, and duraplasty. Testing was repeated 6 months after surgery.

Conclusions. Peak intrathecal pressures during cough and at baseline were elevated in patients with headache associated with cough compared with either patients without headache or healthy volunteers. After surgery, intrathecal pressures during cough were significantly lower than preoperative values and headache aggravated by cough was resolved partially or completely. Headache linked to coughing in patients with Chiari I malformation is associated with sudden increased intrathecal pressure caused by obstruction to the free flow of CSF in the subarachnoid space.
Symptom-based assessment of the severity of a concussion
Authors: Erlanger David , Kaushik Tanya , Cantu Robert , Barth Jeffrey T. , Broshek Donna K. , Freeman Jason R. , Webbe Frank M.
Published: May 2009

Object. Current grading systems of concussion and return-to-play guidelines have little empirical support. The authors therefore examined the relationships of the characteristics and symptoms of concussion and the history of concussion to three indicators of concussion severity—number of immediate symptoms, number of symptoms at the initial follow-up examination, and duration of symptoms—to establish an empirical basis for grading concussions.

Methods. Forty-seven athletes who sustained concussions were administered alternate forms of an Internet-based neurocognitive test until their performances were within normal limits relative to baseline levels. Assessments of observer-reported and self-reported symptoms at the sideline of the playing field on the day of injury, and at follow-up examinations were also obtained as part of a comprehensive concussion management protocol.

Although loss of consciousness (LOC) was a useful indicator of the initial severity of the injury, it did not correlate with other indices of concussion severity, including duration of symptoms. Athletes reporting memory problems at follow-up examinations had significantly more symptoms in general, longer durations of those symptoms, and significant decreases in scores on neurocognitive tests administered approximately 48 hours postinjury. This decline of scores on neurocognitive testing was significantly associated with an increased duration of symptoms. A history of concussion was unrelated to the number and duration of symptoms.

Conclusions. This paper represents the first documentation of empirically derived indicators of the clinical course of postconcussion symptom resolution. Self-reported memory problems apparent 24 hours postconcussion were robust indicators of the severity of sports-related concussion and should be a primary consideration in determining an athlete's readiness to return to competition. A decline on neurocognitive testing was the only objective measure significantly related to the duration of symptoms. Neither a brief LOC nor a history of concussion was a useful predictor of the duration of postconcussion symptoms.
Framework for bioethical assessment of an article on therapy
Authors: Bernstein Mark , Upshur Ross E. G.
Published: May 2009

Object. Frameworks for scientific assessment of articles on therapy published in the medical literature have become available and will likely enhance the quality of medical research that is published in peer-reviewed journals. Comprehensive frameworks do not exist for the assessment of bioethical issues pertaining to research on human volunteers.

Methods. The authors have developed a framework consisting of ethical dimensions or questions that they suggest should be applied to assess the bioethical integrity of articles on therapy. Thirteen questions were developed and discussed in the context of current bioethical principles, and examples were applied where possible.

Conclusions. The simple framework the authors have developed offers a method to assess key bioethical issues surrounding an article on therapy and probably defines the minimum standard to which such articles should be held. Many ethical questions cannot yet be answered based on available information or bioethical theories. The authors are not suggesting that their framework is comprehensive; refinements and individualization of it to fit specific studies are probably required by each clinician—researcher who designs a therapy trial and reports its results.
Use of a wedged microcatheter for curative transarterial embolization of complex intracranial dural arteriovenous fistulas: indications, endovascular technique, and outcome in 21 patients
Authors: Nelson Peter Kim , Russell Stephen M. , Woo Henry H. , Alastra Anthony J. G. , Vidovich Danko V.
Published: May 2009

Object. The aim of this study was to describe the application of a novel transarterial approach to curative embolization of complex intracranial dural arteriovenous fistulas (DAVFs). This technique is particularly useful in patients harboring high-grade DAVFs with direct cortical venous drainage or for whom transvenous coil embolization is not possible because of limited sinus venous access to the fistula site due to thrombosis or stenotic changes.

Methods. Twenty-three DAVFs in 21 patients were treated using a transarterial N-butyl cyanoacrylate (NBCA) embolization technique with the aid of a wedged catheter. In all patients, definitive treatment involved two critical steps: 1) a microcatheter was wedged within a feeding artery, establishing flow-arrest conditions within the catheterized vessel distal to the microcatheter tip; and 2) NBCA was injected under these resultant flow-arrest conditions across the pathological arteriovenous connection and into the immediate draining venous apparatus, definitively occluding the fistula. Patient data were collected in a retrospective manner by reviewing office and inpatient charts and embolization reports, and by directly analyzing all procedural and diagnostic angiograms.

Eight patients presented with the principal complaint of tinnitus/bruit, five with intracranial hemorrhage, four with cavernous sinus syndrome, and one each with seizures, ataxia, visual field loss, and hiccups. The parent (recipient) venous structure of the DAVFs in this study included 11 leptomeningeal veins, eight transverse/sigmoid sinuses, three cavernous sinuses, and one sphenoparietal sinus. The NBCA permeated the arteriovenous shunt, perifistulous network, and proximal draining vein in all DAVFs. Occlusion was confirmed on postembolization angiography studies. No complication occurred in any patient in this series. There has been no recurrence during a mean follow up of 18.7 months (range 2–46 months).

Conclusions. Transarterial NBCA embolization with the aid of a wedged catheter in flow-arrest conditions is a safe and an effective treatment for intracranial DAVFs.
Intraoperative monitoring of blood flow insufficiency in the anterior choroidal artery during aneurysm surgery
Authors: Suzuki Kyouichi , Kodama Namio , Sasaki Tatsuya , Matsumoto Masato , Konno Yutaka , Sakuma Jun , Oinuma Masahiro , Murakawa Masahiro
Published: May 2009

Object. The lack of a specified intraoperative method for monitoring anterior choroidal artery (AChA) blood flow insufficiency (BFI) led the authors to devise a method for checking the BFI in this artery during aneurysm surgery. To this end, the authors relied on the intraoperative motor evoked potentials (MEPs) elicited by electrical stimulation of the hand motor cortex.

Methods. The study population consisted of 108 patients with internal carotid artery (ICA) aneurysms who underwent surgery via a standard frontotemporal craniotomy. After the dura mater had been opened, a grid electrode strip with 16 small electrodes was inserted subdurally into the hand motor cortex from the edge of the craniotomy. To check BFI in the AChA, the hand motor cortex was stimulated at an intensity level between 10 and 18 mA. The MEPs were successfully recorded from the contralateral thenar muscles in all 108 patients. There was no postoperative motor paresis in 88 patients in whom the MEPs remained unchanged during the performance of various surgical maneuvers. Among the other 20 patients, 19 manifested transient MEP changes, but 15 of those patients experienced no postoperative motor paresis. In four patients who exhibited transient MEP changes, either after aneurysm clipping or during temporary occlusion of the ICA and/or AChA, hemiparesis occurred postoperatively but disappeared within 24 hours. In one patient with an ICA—posterior communicating artery aneurysm, the MEP disappeared and did not reappear by the time of dural closure. Severe hemiplegia developed in this patient and a computerized tomography scan obtained postoperatively revealed a new low-density area in the internal capsule.

Conclusions. The findings of this study suggest that the monitoring method that is introduced here is safe and reliable for detecting intraoperative BFI in the AChA.
Monitoring of brain tissue oxygenation during aneurysm surgery: prediction of procedure-related ischemic events
Authors: Jödicke Andreas , Hübner Felix , Böker Dieter-Karsten
Published: May 2009

Object. The aim of this study was to evaluate the feasibility of monitoring brain tissue oxygenation (PO2) during aneurysm surgery for the detection of procedure-related ischemia.

Methods. Between 1997 and 1998, PO2 was monitored prospectively in a cohort of 40 patients (42 recordings) during aneurysm surgery in the anterior circulation within the vascular territory of the aneurysm-bearing artery. The position of the probe used to measure oxygenation levels was verified on computerized tomography (CT) scanning on the 1st postoperative day. Because of the mislocation of one probe and the malfunction of another, data from only 38 patients (40 recordings) were suitable for analysis. Relative changes from baseline to absolute nadir values of intraoperative PO2 were correlated with simultaneously recorded somatosensory evoked potentials (SSEPs), and cardiovascular and ventilatory parameters. The frequency of ischemic events was evaluated with the aid of CT on the 1st postoperative day as a substitute parameter for intraoperative ischemia. Clinical outcome was evaluated 30 days postoperatively based on the Glasgow Outcome Scale.

Except for three, all patients underwent surgery for treatment of a symptomatic aneurysm. Mean baseline PO2 was 23.9 mm Hg (range 2–67.2 mm Hg) before clip application. A relative decrease in PO2 (20% decrease in value compared with baseline) occurred in 12 patients and was a sensitive indicator for the risk of ischemia during temporary arterial occlusion, but was less predictive of nonocclusive ischemia (sensitivity 0.5; positive predictive value [PPV] 0.42; p > 0.05). Results of receiver operating characteristic analysis demonstrated a postclipping PO2 nadir of 15 mm Hg as a dichotomizing threshold for the prediction of ischemia. This threshold rendered an improved sensitivity (0.9) and PPV (0.56) for procedure-related ischemia (p = 0.0003). The results of utility analysis revealed this monitoring parameter to be clinically diagnostic. Only PO2 monitoring, and not SSEP at the tibial nerve, was predictive of ischemia within the anterior cerebral artery territory.

Conclusions. Using 15 mm Hg as a dichotomizing threshold, intraoperative PO2 monitoring enables one to identify patients at risk for procedure-related ischemia during aneurysm surgery and surpasses SSEP monitoring. This newly defined threshold based on intraoperative PO2 monitoring provides a basis for studies on treatments for procedure-related ischemia during aneurysm surgery.
Three-dimensional angiography for radiosurgical treatment planning for arteriovenous malformations
Authors: Colombo Federico , Cavedon Carlo , Francescon Paolo , Casentini Leopoldo , Fornezza Umberto , Castellan Lucio , Causin Francesco , Perini Stefano
Published: May 2009

Object. Radiosurgical treatment of a cerebral arteriovenous malformation (AVM) requires the precise definition of the nidus of the lesion in stereotactic space. This cannot be accomplished using simple stereotactic angiography, but requires a combination of stereotactic biplanar angiographic images and stereotactic contrast-enhanced computerized tomography (CT) scans. In the present study the authors describe a method in which three-dimensional (3D) rotational angiography is integrated into stereotactic space to aid treatment planning for radiosurgery.

Methods. Twenty patients harboring AVMs underwent treatment planning prior to linear accelerator radiosurgery. Planning involved the acquisition of two different data sets, one of which was obtained using the standard method (a combination of biplanar stereotactic angiography with stereotactic CT scanning), and the other, which was procured using a new technique (nonstereotactic 3D rotational angiography combined with stereotactic CT scanning by a procedure of image fusion).

The treatment plan that was developed using the new method was compared with that developed using the standard one. For each patient the number of isocenters and the dimension of selected collimators were the same, based on the information supplied in both methods. Target coordinates were modified in only five cases and by a limited amount (mean 0.7 mm, range 0.3–1 mm).

Conclusions. The new imaging modality offers an easier and more immediate interpretation of 3D data, while maintaining the same accuracy in target definition as that provided by the standard technique. Moreover, the new method has the advantage of using nonstereotactic 3D angiography, which can be performed at a different site and a different time with respect to the irradiation procedure.
In vivo model of intracranial stent implantation: a pilot study to examine the histological response of cerebral vessels after randomized implantation of heparin-coated and uncoated endoluminal stents in a blinded fashion
Authors: Levy Elad I. , Boulos Alan S. , Hanel Ricardo A. , Tio Fermin O. , Alberico Ronald A. , Fronckowiak Mary Duffy , Nemes Balazs , Paciorek Ann Marie , Guterman Lee R. , Hopkins L. Nelson
Published: May 2009

Object. No animal model currently exists for the examination of time-dependent histological changes occurring in intracranial vessels after endoluminal stent placement. The authors' goal was to develop a reproducible in vivo model of stent implantation in intracranial vessels in dogs that was capable of demonstrating stent-related vascular changes after the implantation of coated and uncoated devices.

Methods. The authors implanted heparin-coated or uncoated stents in the basilar arteries (BAs) of 11 mongrel dogs. In a 12th animal, one coated stent was implanted in the BA and a second uncoated one was implanted in the distal anterior spinal artery. All the devices were oversized to induce intimal injury. Surviving animals were observed for 12 weeks, after which they underwent repeated angiography before planned death and removal of the brain. Histological studies and computer-assisted morphometric analyses were conducted on stent-treated and untreated sections of the BAs to assess the percentage of stenosis, neointimal proliferation, vessel injury, and inflammation. Perforating vessels partially covered by stent struts (“jailing”) were studied for evidence of stenosis or occlusion. The pathologist, interventionists, histopathologist, histopathology technicians, and radiologist were blinded to the stent type.

Seven stents (three uncoated and four coated) were removed from the six animals that were observed during the follow-up period. The mean neointimal proliferation was 0.42 mm2 in the group treated with uncoated stents and 0.18 mm2 in the group treated with heparin-coated devices (p = 0.04). Neointimal thickness was significantly increased in the group with uncoated stents (p = 0.04). The mean percentage of occlusion was less (12%) in the group with heparin-coated stents, compared with 22% in the group with uncoated devices (p = 0.07). When comparing results between the heparin-coated and uncoated devices implanted in the five animals that received a single stent only, greater differences (indicating a benefit from heparin-coated stents) were observed in neointimal area (p = 0.009), neointima/media ratio (p = 0.001), neointimal thickness (p = 0.002), and percentage of occlusion (p = 0.009). All brainstem perforating vessels covered by stent struts remained patent.

Conclusions. This in vivo intracranial stent model was developed to assess proliferative and inflammatory responses to endoluminal stent implantation in the cerebrovasculature. The results indicate that a lower percentage of occlusion occurs 12 weeks after implantation of heparin-coated compared with uncoated stents.
Adenosine-induced modulation of excitatory amino acid transport across isolated brain arterioles
Authors: Grant Gerald A. , Meno Joseph R. , Nguyen Thien-Son , Stanness Kathe A. , Janigro Damir , Winn H. Richard
Published: May 2009

Object. Excitatory amino acid (EAA) uptake by neurons and glia acts synergistically with stereoselective transport across the blood—brain barrier (BBB) to maintain EAA homeostasis in the brain. The endogenous neuroprotectant adenosine counteracts many aspects of excitotoxicity by increasing cerebral blood flow and by producing pre- and postsynaptic actions on neurons. In the present study, the authors explored the effect of adenosine on EAA transport across the BBB.

Methods. The effects of adenosine on the permeability of the BBB and transport of aspartate and glutamate across the BBB were studied in a well-characterized isolated penetrating cerebral arteriole preparation suitable for simultaneous investigations of changes in diameter and permeability. At concentrations within the physiological to low pathophysiological range (10−7–10−6 M), the net vectorial transport of [3H]l-glutamate or [3H]l-aspartate from blood to brain was significantly attenuated, whereas there was no effect of adenosine on paracellular BBB permeability to [14C]sucrose or [3H]d-aspartate. With higher concentrations of adenosine (10−4 M and 10−3 M) the net vectorial transport of [3H]l-glutamate and [3H]l-aspartate returned toward baseline. At 10−3 M, the permeability to [14C]sucrose was significantly altered, indicating a breakdown in the BBB. The effect of adenosine (10−6 M) was blocked by theophylline, a blocker of the A1 and A2 receptors of adenosine.

Conclusions. Adenosine-mediated modulation of glutamate and aspartate transport across the BBB is a novel physiological finding.
Delayed repletion of O6-methylguanine—DNA methyltransferase resulting in failure to protect the human glioblastoma cell line SF767 from temozolomide-induced cytotoxicity
Authors: Hirose Yuichi , Kreklau Emiko L. , Erickson Leonard C. , Berger Mitchel S. , Pieper Russell O.
Published: May 2009

Object. Temozolomide (TMZ)-induced O6-methylguanine (MG) DNA lesions, if not removed by MG—DNA methyltransferase (MGMT), mispair with thymine, trigger rounds of futile mismatch repair (MMR), and in glioma cells lead to prolonged G2—M arrest and ultimately cell death. Depletion of MGMT by O6-benzylguanine (BG) sensitizes tumor cells to TMZ, and this combination is currently used in clinical trials. The use of the TMZ+BG combination in gliomas, however, is complicated by the prolonged TMZ-induced G2—M arrest, which may delay activation of poorly defined cell death pathways and allow for MGMT repletion and reversal of toxicity.

Methods. To address these issues, the actions of TMZ were monitored in DNA MMR-proficient SF767 glioma cells depleted of MGMT by BG, and in cells in which BG was removed at various times after TMZ exposure. In MGMT-depleted cells, TMZ exposure led to DNA single-strand breaks and phosphorylation of cdc2, followed by G2—M arrest, induction of p53/p21, and DNA double-strand breaks. Although DNA single-strand breaks, phosphorylation of cdc2, and G2—M arrest could be reversed by repletion of MGMT up to 5 days after TMZ exposure, TMZ-induced cytotoxicity could only be prevented if MGMT was replenished within 24 hours of the onset of G2—M arrest, and before the creation of DNA double-strand breaks.

Conclusions. These results indicate that although SF767 glioma cells undergo a prolonged G2—M arrest in response to TMZ, their ability to escape TMZ-induced cytotoxicity by MGMT repletion is limited to an approximately 24-hour period after the onset of G2—M arrest.
Theodore Brown Rasmussen (1910–2002): epilepsy surgeon, scientist, and teacher
Authors: Feindel William
Published: May 2009

✓ Theodore Brown Rasmussen succeeded Wilder Penfield as director of the Montreal Neurological Institute (MNI) and held this post from 1960 to 1972. During his career, Rasmussen probably performed more operations for epilepsy than any other surgeon of his time; he became the foremost authority in this field. His meticulous follow-up analyses of the MNI seizure series provided substantial evidence for the success of surgery in the treatment of focal epilepsy. In addition, he made significant contributions to surgery of the pituitary gland for control of cancer, treatment of cerebral and spinal tumors, application of the intracarotid Amytal test for lateralization of speech and memory function, and characterization and treatment of epilepsy accompanied by chronic encephalitis, now referred to as Rasmussen syndrome. His painstaking attention to surgical details as well as his insistence on close monitoring of patient care and critical scrutiny of clinical results marked him as an outstanding teacher and role model for young neurosurgeons and neuroscientists.
Assessment of long-term remission of acromegaly following surgery
Authors: Krieger Mark D. , Couldwell William T. , Weiss Martin H.
Published: May 2009

Object. The criteria for remission of acromegaly following transsphenoidal adenoma resection are in evolution. In the present study the authors evaluate the utility of predicting long-term remission by reference to a single fasting growth hormone (GH) level on the 1st postoperative day.

Methods. A retrospective analysis was conducted on 181 patients with acromegaly who underwent transsphenoidal resection between 1973 and 1990 and completed a 5-year follow-up period. Fasting serum GH levels were obtained in all patients on the 1st postoperative day in the absence of exogenous glucocorticoids. All patients participated in a follow-up evaluation lasting at least 5 years, which included measurements of serum insulin-like growth factor—I (IGF-I) levels as an index of acromegalic activity.

Among the 181 patients, GH levels ranged from 0 to 8 ng/ml in 131 (72%) on the 1st postoperative day, suggesting biochemical remission. This group included 107 (84%) of the 127 patients with microadenomas, but only 24 (44%) of the 54 with macroadenomas. Nevertheless, 15 (11%) of the 131 patients who initially had attenuated GH levels displayed recurrent acromegaly within the first 2 years (with elevated levels of IGF-I in all cases, and abnormalities appearing on magnetic resonance images in nine cases). Only one of 116 patients in whom the initial postoperative GH level was lower than 2 ng/ml experienced a recurrence, whereas 14 (93%) of the 15 patients with postoperative GH levels between 2.2 and 8 ng/ml subsequently displayed biochemical evidence of acromegaly.

Conclusions. The findings indicate that a fasting morning serum GH level lower than 2 ng/ml on the 1st postoperative day portends long-term biochemical remission of acromegaly, whereas higher levels are a significant marker for recurrent disease.
Efficacy of antimicrobial-impregnated external ventricular drain catheters: a prospective, randomized, controlled trial
Authors: Zabramski Joseph M. , Whiting Donald , Darouiche Rabih O. , Horner Terry G. , Olson Jeffrey , Robertson Claudia , Hamilton Allan J.
Published: May 2009

Object. Catheter-related infection of the cerebrospinal fluid (CSF) pathways is a potentially life-threatening complication of external ventricular drainage. A major source of infection is bacterial contamination along the external ventricular drain (EVD) catheter track. The authors examined the efficacy of EVD catheters impregnated with minocycline and rifampin in preventing these catheter-related infections.

Methods. The authors conducted a prospective, randomized clinical trial at six academic medical centers. All hospitalized patients 18 years or older who required placement of an EVD catheter were eligible for inclusion in the study. Patients were randomly assigned to undergo placement of an EVD with a catheter impregnated with minocycline and rifampin or a standard untreated catheter (control group). To assess primary outcome, CSF samples were collected using a sterile technique at the time of catheter insertion, at least every 72 hours while the catheter remained in place, and at the time of catheter removal. At the time of removal, CSF cultures were obtained from the tip and tunneled segments of each catheter by performing semiquantitative roll-plate and quantitative sonication techniques.

Of the 306 patients enrolled in the study, data from 288 were included in the final analysis. Eighteen patients were excluded from analysis: 14 because the ventricular catheter was in place less than 24 hours, and four because CSF cultures obtained at the time of catheter insertion were positive for infection. Of these 288 patients, 139 were assigned to the control group and 149 to the treatment group. The two groups were well matched with respect to all clinical characteristics, including patient sex and mean age, indication for catheter placement, and length of time the catheter remained in place. The antibiotic-impregnated catheters were one half as likely to become colonized as the control catheters (17.9 compared with 36.7%, respectively, p < 0.0012). Positive CSF cultures were seven times less frequent in patients with antibiotic-impregnated catheters compared with those in the control group (1.3 compared with 9.4%, respectively, p = 0.002).

Conclusions. The use of EVD catheters impregnated with minocycline and rifampin can significantly reduce the risk of catheter-related infections.
Clinical significance of elevated troponin I levels in patients with nontraumatic subarachnoid hemorrhage
Authors: Deibert Ellen , Barzilai Benico , Braverman Alan C. , Edwards Dorothy Farrar , Aiyagari Venkatesh , Dacey Ralph , Diringer Michael
Published: May 2009

Object. Aneurysmal subarachnoid hemorrhage (SAH) is associated with electrocardiographic abnormalities, regional or focal wall-motion abnormalities on echocardiograms, and/or increased creatine kinase MB isoenzyme (CK-MB) or cardiac troponin I (cTnI). The goal of this prospective study was to compare the sensitivity and specificity of cTnI with those of CK-MB in the prediction of left ventricular dysfunction on echocardiograms in patients with nontraumatic SAH. In addition, those patients with abnormal findings on their echocardiograms and elevated cTnI levels were further evaluated for the presence of coronary artery disease (CAD) by a cardiologist and to determine whether any left ventricular dysfunction that had been detected was reversible.

Methods. The authors obtained electrocardiograms and echocardiograms, and measured serial levels of cardiac enzymes (CK-MB and cTnI) in 43 patients with nontraumatic SAH. Patients with known CAD were excluded. Those patients found to have elevated enzyme levels and abnormal findings on their echocardiograms underwent additional evaluation for CAD. The sensitivity and specificity of both cTnI and CK-MB for detecting left ventricular function were determined.

Twenty-eight percent of patients with SAH in the study had elevated cTnI levels within the first 24 hours after hemorrhage. Seven of the 12 patients had evidence of left ventricular dysfunction on echocardiograms. In all these patients a return to baseline function was found during follow-up examinations. The authors found that cTnI is much more sensitive than CK-MB (100% compared with 29%) in the detection of left ventricular dysfunction in patients with SAH.

Conclusions. An elevated level of cTnI is a good indicator of left ventricular dysfunction in patients with SAH. In this study cardiac dysfunction was reversible and should not necessarily preclude these patients from undergoing operative interventions or becoming heart donors. Clinical management may require more aggressive hemodynamic monitoring until cardiac function returns to normal.
Chronic stimulation of the globus pallidus internus for treatment of non-DYT1 generalized dystonia and choreoathetosis: 2-year follow up
Authors: Krauss Joachim K. , Loher Thomas J. , Weigel Ralf , Capelle H. Holger , Weber Sabine , Burgunder Jean-Marc
Published: May 2009

Object. The authors studied the long-term efficacy of deep brain stimulation (DBS) of the posteroventral lateral globus pallidus internus up to 2 years postoperatively in patients with primary non-DYT1 generalized dystonia or choreoathetosis. The results are briefly compared with those reported for DBS in DYT1 dystonia (Oppenheim dystonia), which is caused by the DYT1 gene.

Methods. Enrollment in this prospective expanded pilot study was limited to adult patients with severely disabling, medically refractory non-DYT1 generalized dystonia or choreoathetosis. Six consecutive patients underwent follow-up examinations at defined intervals of 3 months, 1 year, and 2 years postsurgery. There were five women and one man, and their mean age at surgery was 45.5 years. Formal assessments included both the Burke-Fahn-Marsden dystonia scale and the recently developed Unified Dystonia Rating Scale. Two patients had primary generalized non-DYT1 dystonia, and four suffered from choreoathetosis secondary to infantile cerebral palsy. Bilateral quadripolar DBS electrodes were implanted in all instances, except in one patient with markedly asymmetrical symptoms. There were no adverse events related to surgery.

The Burke-Fahn-Marsden scores in the two patients with generalized dystonia improved by 78 and 71% at 3 months, by 82 and 69% at 1 year, and by 78 and 70% at 2 years postoperatively. This was paralleled by marked amelioration of disability scores. The mean improvement in Burke-Fahn-Marsden scores in patients with choreoathetosis was 12% at 3 months, 29% at 1 year, and 23% at 2 years postoperatively, which was not significant. Two of these patients thought that they had achieved marked improvement at 2 years postoperatively, although results of objective evaluations were less impressive. In these two patients there was a minor but stable improvement in disability scores. All patients had an improvement in pain scores at the 2-year follow-up review. Medication was tapered off in both patients with generalized dystonia and reduced in two of the patients with choreoathetosis. All stimulation-induced side effects were reversible on adjustment of the DBS settings. Energy consumption of the batteries was considerably higher than in patients with Parkinson disease.

Conclusions. Chronic pallidal DBS is a safe and effective procedure in generalized non-DYT1 dystonia, and it may become the procedure of choice in patients with medically refractory dystonia. Postoperative improvement of choreoathetosis is more modest and varied, and subjective ratings of outcome may exceed objective evaluations.
Hyperemia prior to acute brain swelling during rewarming of patients who have been treated with moderate hypothermia for severe head injuries
Authors: Iida Koji , Kurisu Kaoru , Arita Kazunori , Ohtani Minako
Published: May 2009

Object. The goal of this study was to elucidate the optimal time for rewarming of patients who have been treated with hypothermia for severe head injury.

Methods. Eleven patients with severe head injuries who had been treated by hypothermia underwent transcranial Doppler (TCD) ultrasonography examinations. The patients were divided into two groups: Group A consisted of three patients in whom acute brain swelling occurred during the rewarming period and Group B was composed of eight patients who displayed no significant intracranial hypertension during or after hypothermia therapy. In all patients, the mean flow velocity of the middle cerebral artery (FVMCA) recorded transcranially and the mean flow velocity of the internal carotid artery (FVICA), recorded high in the neck, were monitored at 24-hour intervals after the patient was admitted to the hospital. In Group A, the FVMCA was normal at 48 hours (maintenance state of hypothermia) in each patient, and abnormal increases and peak values (> 100 cm/second) occurred from 96 to 144 hours postinjury (rewarming period). The FVICA, which was monitored concurrently also varied as the FVMCA increased. The pulsatility indices in the arteries decreased at the time of the peak FVMCA. The enhanced FVMCA was consistent with hyperemia because of the low FVMCA/FVICA ratios (< 3). Two patients in whom jugular venous oxygen saturation was monitored were found to have high values (> 80%), representing hyperemia. All intracranial pressures (ICPs) that lay within the normal range at 48 hours postinjury elevated acutely after the peak FVMCA. In Group B, both FVMCA and FVICA values were normal at 48 hours postinjury and remained stable throughout the rewarming period. Values of ICP were also maintained within the normal range until the patients were weaned from hypothermia therapy.

Conclusions. Hyperemia, detectable by TCD ultrasonography, may serve as an index in the prediction of acute brain swelling, and rewarming should be terminated when such a hemodynamic phenomenon is observed.