bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypoxia in the tumorigenesis of gliomas and as a potential target for therapeutic measures
Authors: Jensen Randy L.
Published: January 2008

✓ In this article, the author provides a brief description of the role of hypoxia in the tumorigenesis of gliomas and suggests potential ways of exploiting this role to design treatment modalities. Tumor hypoxia predicts the likelihood of metastases, tumor recurrence, resistance to chemotherapy and radiation therapy, invasive potential, and decreased patient survival for many human malignancies. Various methods of measurement of tumor hypoxia are discussed, including direct measurement and imaging methods.

The role of hypoxia-responsive molecules, especially hypoxia-inducible factor-1 (HIF-1), in glioma tumorigenesis is explored. Treatment modalities regulated by hypoxia are proposed and some potential strategies reviewed. The progression of a low-grade astrocytoma to a glioblastoma multiforme may be mediated by hypoxia-induced phenotypic changes and subsequent clonal selection of cells that overexpress hypoxia-responsive molecules, such as HIF-1. In this model, intratumoral hypoxia causes genetic changes that produce a microenvironment that selects for cells of a more aggressive phenotype.
Convection-enhanced delivery of immunotoxins and radioisotopes for treatment of malignant gliomas
Authors: Vandergrift William A. , Patel Sunil J.
Published: January 2008

✓ The treatment of malignant gliomas has advanced significantly in the past 15 years. The simultaneous development of new targeting agents and techniques to deliver these high-molecular-weight compounds has led to improved efficacy and promising results in Phase III trials. Convection-enhanced delivery (CED) of macromolecules has emerged as the leading delivery technique for the treatment of malignant gliomas. A summary of the basic principles of CED and a review of the current human trials of protein targeting agents are provided.
Comparison of intratumoral bolus injection and convection-enhanced delivery of radiolabeled antitenascin monoclonal antibodies
Authors: Sampson John H. , Akabani Gamal , Friedman Allan H. , Bigner Darell , Kunwar Sandeep , Berger Mitchel S. , Bankiewicz Krystof S.
Published: January 2008

Objectives

Convection-enhanced delivery (CED) is a novel technique used to deliver agents to the brain parenchyma for treatment of neoplastic, infectious, and degenerative conditions. The purpose of this study was to determine if CED would provide a larger volume of distribution (Vd) of a radiolabeled monoclonal antibody (mAb) than a bolus injection.

Methods

Patients harboring a recurrent glioblastoma multiforme that reacted with the antitenascin mAb 81C6 during immunohistochemical analysis were randomized to receive an intratumoral injection of the human–murine chimeric mAb Ch81C6, which had been labeled with the 123I tracer. The mAb was administered by either a bolus injection or CED via a stereotactically placed catheter; between 48 and 72 hours later the mAb was again administered using the other technique. Injections of escalating doses of a 131I-labeled therapeutic mAb were then delivered using the technique shown to produce the largest Vd by single-photon emission computerized tomography.

Conclusions

Convection-enhanced delivery has enormous potential for administering drugs to sites within the central nervous system. For the relatively small volumes injected in this study, however, CED did not provide a significant increase in the Vd when compared with the bolus injection. Nevertheless, a clear cross-over effect was seen, which was probably related to the temporal proximity of the two infusions.
History of surgery for cerebrovascular disease in children. Part II. Vein of Galen malformations
Authors: Blount Jeffrey P. , Oakes W. Jerry , Tubbs R. Shane , Humphreys Robin P.
Published: January 2008

✓ Vein of Galen aneurysmal malformations are a mixed group of lesions characterized by an abnormal fistula between abnormal distal branches of the choroidal and/or posterior cerebral arteries and the great vein of Galen. In this paper the authors trace the historical evolution of the current approach to diagnosis and treatment, and the literature is reviewed comprehensively. During the historical era, vein of Galen malformations were described in individual case reports and an early classification system was developed. In the early era of treatment, open surgery was the preferred approach, although morbidity and mortality rates were high. The development of neurointerventional techniques allowed the introduction of occlusive materials into the fistula, with pronounced improvements in clinical outcome.
History of surgery for cerebrovascular disease in children. Part III. Arteriovenous malformations
Authors: Blount Jeffrey P. , Tubbs R. Shane , Oakes W. Jerry , Humphreys Robin P.
Published: January 2008

✓ Arteriovenous malformations (AVMs) are the most common cause of intracerebral hemorrhage in children. In this paper the authors trace the historical evolution of the recognition, diagnosis, and treatment of pediatric intracerebral AVMs, and they summarize the contemporary approach and current controversies surrounding treatment of these lesions. Important distinctions between adult and pediatric AVMs are emphasized.
The transition from hunterian ligation to intracranial aneurysm clips: a historical perspective
Authors: Polevaya Nika V. , Kalani M. Yashar S. , Steinberg Gary K. , Tse Victor C. K.
Published: January 2008

✓ The description of cerebral aneurysms dates back to antiquity. Little was known, however, about the pathological mechanisms of aneurysm formation and treatment options for this disease until 200 years ago. The modern era of aneurysm treatment began with the hunterian ligation of the proximal artery, followed by clip and coil occlusion. In this article, the authors describe the transition from conservative therapy to internal carotid artery (ICA) ligation and gradual occlusion of the ICA to the direct placement of clips on aneurysms. The driving forces and rationale behind each major advancement are summarized, and the authors attempt to predict what these innovations mean for the future of intracranial aneurysm management.
Neurosurgical management of cerebellar cavernous malformations
Authors: de Oliveira Jean G. , Rassi-Neto Aziz , Ferraz Fernando A. P. , Braga Fernando M.
Published: January 2008

Object

The aim of this study was to analyze cerebellar cavernous malformations (CMs) with respect to epide-miological, clinical, radiological, and therapeutic aspects.

Methods

Between 1984 and 2004, 100 patients were surgically treated for intracranial CMs at the Division of Neurosurgery of Federal University of São Paulo. The authors reviewed the records of 10 patients whose lesions were located in the cerebellum.

There were four male and six female patients (ratio 1:1.5) whose ages ranged from 14 to 45 years (mean age 33 years). Clinical presentation was sudden or acute in all cases, and neuroimaging examinations performed in all patients demonstrated signs of bleeding. The mean size of the malformations was 4.6 cm, and in all but one patient the lesions were totally removed without complications. After a mean follow-up period of 70 months, all patients were considered to be in good or excellent clinical condition.

Conclusions

Cerebellar CMs should be analyzed separately from other posterior fossa CMs. These lesions can reach large sizes and cause massive hemorrhages, resulting in acute or sudden presentation. Surgery is a safe and effective option that provides a curative treatment when a complete removal is achieved.
Hemorrhage of cavernous malformations during pregnancy and in the peripartum period: causal or coincidence?
Authors: Safavi-Abbasi Sam , Feiz-Erfan Iman , Spetzler Robert F. , Kim Louis , Dogan Seref , Porter Randall W. , Sonntag Volker K. H.
Published: January 2008

✓There is growing evidence to suggest that pregnancy may increase the risk of hemorrhage from cavernous malformations (CMs). In the present case, a 21-year-old primigravida was admitted to the authors' neurosurgical service after a cesarean section. Three weeks before admission she had experienced rapidly progressive bilateral lower-extremity paresthesias. Spinal magnetic resonance (MR) imaging revealed the presence of an intramedullary thoracic lesion. On T2-weighted MR images, heterogeneous signal intensity with a rim of decreased intensity was demonstrated in the spine. The mass was successfully resected, and 1 year later the patient's symptoms had resolved completely. This is the fourth reported case of a spinal intramedullary CM that became symptomatic during pregnancy. The pathogenesis and management of this entity are reviewed.
Molecular genetics of familial cerebral cavernous malformations
Authors: Dashti Shervin R. , Hoffer Alan , Hu Yin C. , Selman Warren R.
Published: January 2008

✓Cerebral cavernous malformations (CMs) are angiographically occult neurovascular lesions that consist of enlarged vascular channels without intervening normal parenchyma. Cavernous malformations can occur as sporadic or auto-somal-dominant inherited conditions. Approximately 50% of Hispanic patients with cerebral CMs have the familial form, compared with 10 to 20% of Caucasian patients. There is no difference in the pathological findings or presentation in the sporadic and familial forms. To date, familial CMs have been attributed to mutations at three different loci: CCM1 on 7q21.2, CCM2 on 7p15-p13, or CCM3 on 3q25.2-q27. The authors summarize the current understanding of the molecular events underlying familial CMs.
Clinical progression and familial occurrence of cerebral cavernous angiomas: the role of angiogenic and growth factors
Authors: Maiuri Francesco , Cappabianca Paolo , Gangemi Michelangelo , De Caro Marialaura Del Basso , Esposito Felice , Pettinato Guido , de Divitiis Oreste , Mignogna Chiara , Strazzullo Viviana , de Divitiis Enrico
Published: January 2008

Object

The authors studied the expression of angiogenic and growth factors and various proliferative indices in cavernous angiomas of the brain. The goal was to define whether the often progressive clinical course of both sporadic and familial forms of the lesion is correlated with different expression of these factors.

Methods

Forty-three cavernomas of the brain were investigated with immunohistochemical studies and stained for four growth factors (vascular endothelial growth factor [VEGF], tenascin, transforming growth factor–β [TGFβ], and platelet-derived growth factor [PDGF]), and for Ki-67 and bcl-2. The intensity of expression was tested in all cases in the walls of cavernoma vessels, in the perivascular tissue, and in the perilesional brain parenchyma. Among the 43 cavernomas, 32 were stable and sporadic single lesions less than 2 cm in size, whereas 11 were cavernomas larger than 2 cm (up to 6 cm). These larger cavernomas had more aggressive behavior (documented growth in five cases, mass effect in eight, significant hemorrhage in four), familial occurrence (six cases), and/or multiple lesions (five cases).

The expression of VEGF, tenascin, and PDGF in cavernomas did not significantly differ in the two groups of patients, whereas TGFβ expression was higher in the more aggressive forms of cavernomas. The expression of Ki-67 and bcl-2 was always absent in stable lesions, and it was positive in eight (72.7%) of 11 aggressive lesions. The perilesional brain parenchyma showed a significantly higher expression of TGFβ, PDGF, and tenascin in more aggressive cavernomas.

Conclusions

The familial occurrence and more aggressive clinical behavior of cavernous angiomas of the brain are associated with higher expression of Ki-67 and bcl-2 in the cavernoma tissue, as in other proliferative lesions. These features are also associated with higher expression of some growth factors (excluding VEGF) in the perilesional brain parenchyma, suggesting that the neighboring vasculature and glia may be predisposed to and recruited for further growth and progression.
The association of venous developmental anomalies and cavernous malformations: pathophysiological, diagnostic, and surgical considerations
Authors: Perrini Paolo , Lanzino Giuseppe
Published: January 2008

✓Developmental venous anomalies (DVAs) are often associated with intracranial cavernous malformations (CMs). The frequency of this association and the observation of de novo CMs located near a known, preexisting DVA raise speculations as to the possible etiopathogenetic relationship between the two. In this article, the authors review the recent literature dealing with the potential etiopathogenetic, prognostic, and therapeutic implications of the association between DVAs and CMs.
Cerebral cavernous malformations and epilepsy
Authors: Awad Issam , Jabbour Pascal
Published: January 2008

✓Seizures and epilepsy are frequent clinical manifestations of cerebral cavernous malformations (CCMs) and represent the most common symptomatic presentation of supratentorial lesions. Clinicians often diagnose CCMs in patients after a first seizure, or in some cases after obtaining neuroimaging studies in patients suffering from chronic epilepsy previously thought to be idiopathic. In some cases, the lesion is clinically significant solely because of its epileptogenicity, but in others there may be concern about potential hemorrhage or focal neurological deficits from a similar lesion.

The authors present current pathophysiological concepts related to epilepsy associated with CCMs. They discuss the spectrum of seizure disorders associated with these lesions and review the natural history, prognosis, and options for therapeutic intervention.
Can angiographic vasospasm be used as a surrogate marker in evaluating therapeutic interventions for cerebral vasospasm?
Authors: Nolan Colum P. , Macdonald R. Loch
Published: January 2008

✓ The authors tested the null hypothesis that published literature with a high level of evidence does not support the assertion that subarachnoid hemorrhage (SAH) causes cerebral vasospasm, which in turn causes cerebral infarction and poor outcome after aneurysmal SAH. The medical literature on SAH was searched in MEDLINE. The author's personal files of all published literature on SAH were reviewed. References cited in Cochrane reviews as well as the published papers that were reviewed were also retrieved.

There is no question that SAH causes what the authors have chosen to call “angiographic vasospasm.” However, the incidence and severity of vasospasm in recent series of patients is not well defined. There is reasonable evidence that vasospasm causes infarction, but again, accurate data on how severe and how diffuse vasospasm has to be to cause infarction and how often vasospasm is the primary cause of infarction are not available. There are good data on the incidence of cerebral infarction after SAH, and these data indicate that it is highly associated with poor outcome. The link between angiographic vasospasm and poor outcome is particularly poorly described in terms of what would be considered data of a high level of evidence.

The question as to whether there is a clear pathway from SAH to vasospasm to cerebral infarction to poor outcome seems so obvious to neurosurgeons as to make it one not worth asking. Nevertheless, the obvious is not always true or accurate, so it is important to note that published literature only weakly supports the causative association of vasospasm with infarction and poor outcome after SAH. It behooves neurosurgeons to document this seemingly straightforward pathway with high-quality evidence acceptable to the proponents of evidence-based medicine.
Effects of acute treatment with statins on cerebral autoregulation in patients after aneurysmal subarachnoid hemorrhage
Authors: Tseng Ming-Yuan , Czosnyka Marek , Richards Hugh , Pickard John D. , Kirkpatrick Peter J.
Published: January 2008

Object

The authors previously have demonstrated that acute treatment with pravastatin after aneurysmal subarachnoid hemorrhage (SAH) can ameliorate vasospasm-related delayed ischemic neurological deficits (DINDs). In the current study, they test the hypothesis that these effects are associated with improvement in indices describing autoregulation of cerebral blood flow.

Methods

In this double-blind study, 80 patients between the ages of 18 and 84 years who had aneurysmal SAH were randomized equally to receive either 40 mg of oral pravastatin or placebo once daily for up to 14 days (medication was started 1.8 ± 1.3 days after ictus). Autoregulation was measured using a daily transient hyperemic response test (THRT) on transcranial Doppler ultrasonography (800 measurements in 80 patients), and data were compared between the pravastatin and placebo groups and between patients with or without vasospasm, DINDs, or unfavorable outcome. Measurement of autoregulation also was performed using the pressure-reactivity index, a moving correlation coefficient between mean arterial and intracranial pressures (Days 0–5, 132 measurements in 32 patients).

There was no difference in baseline autoregulation indices between the trial groups. The members of the pravastatin group not only had a shorter duration of impaired autoregulation but also had stronger transient hyperemic response ratios (THRRs) bilaterally. A negative correlation existed between the mean flow velocity in the middle cerebral artery and THRRs. Onset of DINDs occurred when bilateral autoregulation failed. On Days 3, 4, and 5, the pressure-reactivity index correlated significantly with ipsilateral impaired autoregulation.

Conclusions

The neuroprotective effects of acute treatment with pravastatin following aneurysmal SAH are associated with enhancement of autoregulation. A routine and daily assessment of cerebral autoregulation by using the THRT may help identify patients at high risk of DINDs.
Update on endovascular therapies for cerebral vasospasm induced by aneurysmal subarachnoid hemorrhage
Authors: Sayama Christina M. , Liu James K. , Couldwell William T.
Published: January 2008

✓Cerebral vasospasm remains a major source of morbidity and death in patients with aneurysmal subarachnoid hemorrhage (SAH). When vasospasm becomes refractory to maximal medical management consisting of induced hypertension and hypervolemia and administration of calcium channel antagonists, endovascular therapies should be considered. The primary goal of endovascular treatment is to increase cerebral blood flow to prevent cerebral infarction. Two of the more frequently studied endovascular treatments are transluminal balloon angioplasty and intraarterial papaverine infusion. These two have been used either alone or in combination for the treatment of vasospasm. Other pharmacological vasodilating agents currently being investigated are intraarterial nimodipine, nicardipine, verapamil, and milrinone. Newer intraarterial agents, such as fasudil and colforsin daropate, have also been investigated. In this article the authors review the current options in terms of endovascular therapies for treatment of cerebral vasospasm. The mechanism of action, technique of administration, clinical effect and outcomes, and complications of each modality are discussed.
Safety and technical efficacy of over-the-wire balloons for the treatment of subarachnoid hemorrhage–induced cerebral vasospasm
Authors: Terry Anna , Zipfel Gregory , Milner Eric , Cross DeWitte T. , Moran Christopher J. , Diringer Michael N. , Dacey Ralph G. , Derdeyn Colin P.
Published: January 2008

Object

Over the past decade, low-pressure, flow-directed balloons have been replaced by over-the-wire balloons in the treatment of vasospasm induced by subarachnoid hemorrhage (SAH). The authors assess the procedural safety and technical efficacy of these newer devices.

Methods

Seventy-five patients who underwent 85 balloon angioplasty procedures for the treatment of SAH-induced vasospasm were identified from a prospective quality-assurance database. Medical records and angiographic reports were reviewed for evidence of procedural complications and technical efficacy.

No vessel rupture or perforation occurred, but thromboembolic complications were noted in four (4.7%) of the 85 procedures. Balloon angioplasty was frequently attempted and successfully accomplished in the distal internal carotid (100%), proximal middle cerebral (94%), vertebral (73%), and basilar (88%) arteries. Severe narrowing was present in 89 proximal anterior cerebral arteries. Angioplasty was attempted in 41 of these vessels and was successful in only 14 (34%). In 19 of the 27 unsuccessful attempts, the balloon could not be advanced over the wire due to severe vasospasm or unfavorable vessel angle. Follow-up angiography in a subset of patients demonstrated that severe recurrent vasospasm occurred in 15 (13%) of 116 vessels studied after angioplasty.

Conclusions

Over-the-wire balloons involve a low risk for vessel rupture. The anterior cerebral artery remains difficult to access and successfully treat with current devices. Further improvements in balloon design, such as smaller inflated diameters and better tracking, are necessary. Finally, thromboembolic complications remain an important concern, and severe vasospasm may recur after balloon angioplasty.
Effect of intraarterial verapamil on the diameter of vasospastic intracranial arteries in patients with cerebral vasospasm
Authors: Mazumdar Avi , Rivet Dennis J. , Derdeyn Colin P. , Cross DeWitte T. , Moran Christopher J.
Published: January 2008

Object

This study was conducted to determine whether there is a change in intracranial arterial diameters after verapamil infusion for vasospasm and, if it is present, to determine whether the change occurs in proximal, intermediate, or distal vessels.

Methods

The authors measured arterial diameters in all patients treated with intraarterial verapamil at their institutions between August 2003 and September 2004. In all, 18 treatments were examined in 15 patients. Measurements were made before and after verapamil infusion in a blinded fashion with the aid of a magnification loupe at nine predetermined arterial sites on each angiogram. Baseline arterial measurements were made on each patient's initial angiogram and on the angiogram demonstrating spasm prior to endovascular therapy as well in 14 of the patients. Charts were retrospectively reviewed to determine whether the patients benefited from intraarterial vera-pamil.

From the time of the initial angiogram to the time of vasospasm, there was a 21.6% decrease (p = 0.092) in proximal artery diameter, a 47.1% decrease (p < 0.05) in intermediate artery diameter, and a 12.4% decrease (p < 0.05) in distal artery diameter. There were no significant changes in the diameters of proximal, intermediate, or distal vessels after verapamil infusion (mean dose 7.4 mg, range 2.5–10 mg). After infusion of intraarterial verapamil, the proximal vessels showed a 1.1% decrease in diameter, the intermediate vessels showed a 9.4% increase, and the distal vessels showed a 3.3% decrease.

Conclusions

Administration of intraarterial verapamil does not cause a significant increase in the diameter of vasospastic vessels at the administered doses.
Vasospasm as the sole cause of cerebral ischemia: how strong is the evidence?
Authors: Stein Sherman C. , Levine Joshua M. , Nagpal Seema , LeRoux Peter D.
Published: January 2008

✓ The authors review literature that challenges the view that vasospasm involving large arteries is the exclusive cause of delayed ischemic neurological deficits (DINDs) following subarachnoid hemorrhage. They discuss alternative mechanisms and review the evidence supporting a potential role for thromboembolism. They conclude that vasospasm and thromboembolism play interrelated and additive roles in the development of DINDs, and that this interaction provides opportunities for novel therapeutic approaches.
Utility of computed tomography perfusion in detection of cerebral vasospasm in patients with subarachnoid hemorrhage
Authors: Moftakhar Roham , Rowley Howard A. , Turk Aquilla , Niemann David B. , Kienitz Beverly Aagaard , Van Gomple Jamie , Başkaya Mustafa K.
Published: January 2008

Object

Digital subtraction (DS) angiography is the gold standard for detecting cerebral vasospasm after subarachnoid hemorrhage (SAH). Computed tomography (CT) perfusion is a recently developed modality for the evaluation of cerebral hemodynamics. This study was conducted to evaluate the potential of using CT perfusion to detect vasospasm in patients with SAH.

Methods

Fourteen patients between the ages of 41 and 66 years with aneurysmal SAH underwent 23 CT perfusion scans for suspected vasospasm. All patients underwent DS angiography within 12 hours of the CT perfusion scans. The presence of vasospasm on CT perfusion images was determined based on qualitative reading using color maps of mean transit time, cerebral blood flow, and cerebral blood volume as criteria. The presence or absence of vasospasm as retrospectively determined using CT perfusion was compared with DS angiography findings.

Of the 23 CT perfusion scans performed, 21 (91%) were concordant with angiography findings in predicting the presence or absence of vasospasm. In 15 of 23 scans, the presence of vasospasm was detected on CT perfusion scans and confirmed on DS angiography studies. In two cases, vasospasm was revealed on DS angiography but was not confirmed on CT perfusion. The degree of agreement between CT perfusion and DS angiography for detection of vasospasm was high (κ = 0.8, p < 0.0001).

Conclusions

Computed tomography perfusion is an accurate, reliable, and noninvasive method to detect the presence or absence of vasospasm. It can be used as a tool to help guide the decision to pursue DS angiography with the intent to treat vasospasm.
Cerebral perfusion imaging in vasospasm
Authors: Lad Shivanand P. , Guzman Raphael , Kelly Michael E. , Li Gordon , Lim Michael , Lovbald Karl , Steinberg Gary K.
Published: January 2008

✓Vasospasm following cerebral aneurysm rupture is one of the most devastating sequelae and the most common cause of delayed ischemic neurological deficit (DIND). Because vasospasm also is the most common cause of morbidity and mortality in patients who survive the initial bleeding episode, it is imperative not only to diagnose the condition but also to predict which patients are likely to become symptomatic. The exact pathophysiology of vasospasm is complex and incompletely elucidated. Early recognition of vasospasm is essential because the timely use of several therapeutic interventions can counteract this disease and prevent the occurrence of DIND. However, the prompt implementation of these therapies depends on the ability to predict impending vasospasm or to diagnose it at its early stages.

A number of techniques have been developed during the past several decades to evaluate cerebral perfusion, including positron emission tomography, xenon-enhanced computed tomography, single-photon emission computed tomography, perfusion- and diffusion-weighted magnetic resonance imaging, and perfusion computed tomography. In this article, the authors provide a general overview of the currently available perfusion imaging techniques and their applications in treating vasospasm after a patient has suffered a subarachnoid hemorrhage. The use of cerebral perfusion imaging techniques for the early detection of vasospasm is becoming more common and may provide opportunities for early therapeutic intervention to counteract vasospasm in its earliest stages and prevent the occurrence of DINDs.
A review of current and future medical therapies for cerebral vasospasm following aneurysmal subarachnoid hemorrhage
Authors: Mocco J , Zacharia Brad E. , Komotar Ricardo J. , Connolly E. Sander
Published: January 2008

✓In an effort to help clarify the current state of medical therapy for cerebral vasospasm, the authors reviewed the relevant literature on the established medical therapies used for cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH), and they discuss burgeoning areas of investigation. Despite advances in the treatment of aneurysmal SAH, cerebral vasospasm remains a common complication and has been correlated with a 1.5- to threefold increase in death during the first 2 weeks after hemorrhage. A number of medical, pharmacological, and surgical therapies are currently in use or being investigated in an attempt to reverse cerebral vasospasm, but only a few have proven to be useful. Although much has been elucidated regarding its pathophysiology, the treatment of cerebral vasospasm remains a dilemma. Although a poor understanding of SAH-induced cerebral vasospasm pathophysiology has, to date, hampered the development of therapeutic interventions, current research efforts promise the eventual production of new medical therapies.
Participation in contact or collision sports in athletes with epilepsy, genetic risk factors, structural brain lesions, or history of craniotomy
Authors: Miele Vincent J. , Bailes Julian E. , Martin Neil A.
Published: January 2008

✓Despite a plethora of guidelines for return to play following mild head injury, a discussion of when and if an athlete should be allowed to participate in contact or collision sports if he or she sustains a structural brain lesion or after a head injury requiring craniotomy is lacking. The structural lesions discussed include arachnoid cyst, Chiari malformation Type I, cavum septum pellucidum, and the presence of ventriculoperitoneal shunts. Issues unique to this population with respect to the possibility of increased risk of head injury are addressed. The population of athletes with epilepsy and certain genetic risk factors is also discussed. Finally, the ability of athletes to participate in contact or collision sports after undergoing craniotomies for traumatic or congenital abnormalities is evaluated. Several known instances of athletes returning to contact sports following craniotomy are also reviewed.
Sideline and ringside evaluation for brain and spinal injuries
Authors: Miele Vincent J. , Norwig John A. , Bailes Julian E.
Published: January 2008

✓Participation in contact and collision sports carries an inherent risk of injury to the athlete, with damage to the nervous system producing the most potential for significant morbidity and death. Neurological injuries suffered during athletic competition must be treated promptly and correctly to optimize outcome, and differentiation between minor and serious damage is the foundation of sideline/ringside management of the injury. In this article the authors present a guide to the sideline or ringside identification and management of head and spinal injuries.
Primary diffuse large B-cell lymphoma of the dura mater and cranial vault
Authors: Galarza Marcelo , Gazzeri Roberto , Elfeky Hamed A. , Johnson Robert R.
Published: January 2008

✓ Primary high-grade lymphoma of the dura mater and cranial vault has rarely been reported. The authors treated a 61-year-old man who presented with a slow-growing scalp mass that involved the cranial vertex. Magnetic resonance imaging revealed an oval mass of the dural type with peripheral edema in the bilateral parietal region, with attachment to the cranial vault and extension to the subgaleal space. After subtotal resection, pathological examination yielded a diagnosis of malignant large B-cell lymphoma. Twenty-three months postoperatively, after undergoing radiation therapy and chemotherapy, the patient is neurologically intact and without systemic dissemination of the malignancy. This is a case of primary malignant B-cell lymphoma of the dura mater with extensive involvement of the skull, which is a very rare event. Imaging-based diagnosis and combined therapy consisting of surgery, radiation therapy, and chemotherapy for the disease are discussed, and the literature on extraaxial malignant lymphomas is extensively reviewed.
Chemotherapy for primary central nervous system lymphoma
Authors: Omuro Antonio M. P. , Abrey Lauren E.
Published: January 2008

✓Chemotherapy, with or without radiotherapy, is the mainstay of treatment for primary central nervous system lymphoma (PCNSL). High-dose methotrexate (MTX) is the most effective drug available to treat these lesions, and it is used in doses of 1 to 8 g/m2, either as a single agent or in combination with other drugs such as corticosteroid agents, cytarabine, procarbazine, vincristine, carmustine, lomustine, thiotepa, cyclophosphamide, temozolomide, and rituximab. To date, an overwhelming number of different regimens in which high-dose MTX is used have been reported. Given the lack of randomized trials, however, the optimal treatment remains controversial. Varying methodology makes the comparison of available studies extremely difficult, yet some common themes can be found throughout the literature. Treatment paradigms vary considerably according to the patient's age. Most studies support the use of chemotherapy-only treatments for elderly patients (> 60 years), given the high risks of neurotoxicity associated with radiotherapy. Nevertheless, the prognosis remains poor regardless of the chemotherapy chosen, and less toxic regimens might be preferable for such elderly patients. Conversely, in younger patients (< 60 years), there is growing evidence that commonly used chemotherapy-only regimens are associated with increased relapse rates that may not justify deferral of radiotherapy. Thus, a significant focus of research has been the development of intensified chemotherapy regimens that could replace radiotherapy. In this article, the authors discuss the principles guiding the use of chemotherapy for PCNSL, and critically review the available literature, including the most recent trials.
Surgical interventions for primary central nervous system lymphoma
Authors: Elder James B. , Chen Thomas C.
Published: January 2008

✓ Early diagnosis is central to proper management of primary central nervous system lymphomas (PCNSLs). Surgical intervention hinges on initial entertainment of a diagnosis of a PCNSL, based on acute neurological presentation and neuroimaging findings. Unless there is an urgent need for surgical decompression, a biopsy to obtain a diagnosis of PCNSL is the first step in surgical management. Repeated biopsy may be necessary in patients who have received pre-operative steroid therapy. Patients with PCNSL may also present with leptomeningeal involvement, resulting in the need for an Ommaya reservoir for intrathecal chemotherapy. In cases in which hydrocephalus develops, placement of a ventriculoperitoneal shunt may be necessary. Two case studies are presented to highlight the role of surgical intervention in PCNSL.
Pathology of primary central nervous system lymphoma
Authors: Commins Deborah L.
Published: January 2008

✓ The understanding of primary central nervous system lymphoma (PCNSL) has lagged behind that of the much more common systemic, nodal lymphomas. Reasons for this include the relative rarity of PCNSL and the fact that these lesions differ in some ways from their histologically similar systemic counterparts. The purpose of this paper is twofold: first, the author provides concise descriptions of the pathological features of both common and uncommon types of PCNSL while discussing issues such as the confusion surrounding histological classification of PCNSLs, problems related to intraoperative diagnosis, and the appropriate diagnostic work up. Second, the author discusses a small number of molecular studies to demonstrate the great promise they offer. Such studies have already clarified some issues, including the category of lymphocyte from which the majority of PCNSLs are derived. Hopefully in the future these studies will help guide treatment decisions.
Distinguishing primary central nervous system lymphoma from other central nervous system diseases: a neurosurgical perspective on diagnostic dilemmas and approaches
Authors: Hunt Matthew A. , Jahnke Kristoph , Murillo Tulio P. , Neuwelt Edward A.
Published: January 2008

Object

White matter diseases, including demyelinating or inflammatory disorders, may be indistinguishable clinically and radiologically from some central nervous system (CNS) tumors. In such situations, determination of the final diagnosis is difficult. An example is the differential diagnosis of non-acquired immunodeficiency syndrome–related primary central nervous system lymphoma (PCNSL) and multiple sclerosis (MS), a demyelinating disease. Unfortunately, delayed diagnosis and treatment of PCNSL can negatively affect prognosis.

Methods

The authors reviewed the cases of eight patients with PCNSL or MS. In each case, the initial diagnosis (PCNSL or MS) was equivocal. In these cases, conventional diagnostic approaches were not definitive, thus further delaying diagnosis. The initial symptoms, the selected diagnostic tests, and the presumptive as well as final diagnosis for each case are discussed.

The final diagnosis was PCNSL in six cases and MS in two. The uncertainty about the clinical or initial pathological presentation required further diagnostic evaluation in all cases. Two important neurosurgical guidelines are the avoidance of corticosteroid agents and performance of biopsy sampling rather than volumetric tumor resection. High-volume lumbar puncture, slit-lamp examination/vitrectomy, new CNS imaging techniques, and repeated biopsy procedures also proved helpful.

Conclusions

In PCNSL, early definitive diagnosis and treatment are the keys to successful outcomes. Knowledge of strategies essential to early diagnosis lessens the need for brain biopsy sampling, but this procedure is still usually necessary. In such selected cases, biopsy sampling is appropriate even when pathological investigation shows MS rather than PCNSL. Complete resection is not indicated in PCNSL and can lead to additional sequelae.
Primary central nervous system lymphoma in children
Authors: Abla Oussama , Weitzman Sheila
Published: January 2008

✓ Primary central nervous system lymphoma (PCNSL) is a very rare brain tumor in children, and the optimal management and prognosis of such patients have yet to be defined. In this study, the incidence rate, clinical features, diagnosis, and treatment of childhood PCNSL are reviewed. Except for human immunodeficiency virus–related PCNSL, the prognosis for patients with this tumor type is significantly better in children than in adults. In the absence of prospective studies, it is very difficult to determine the true incidence and the best therapeutic strategy for this rare entity. The majority of children with PCNSL, however, can achieve long-term remissions with intensive chemotherapy alone (an estimated 70% 5-year event-free survival rate), and cranial irradiation can be reserved for relapse of the disease. Further progress in the management of childhood PCNSL will require prospective multinational studies.
Spinal vascular malformations: an historical perspective
Authors: Black Perry
Published: January 2008

✓In this historical perspective, the author identifies three epochs in the development of the concepts and treatment of spinal vascular lesions: 1) early observations (1860s–1912), with the lesions during this time period recognized only at autopsy; 2) the “middle ages” (1912–1960), with surgical intervention sporadic and yielding dismal results; and 3) the modern era (beginning in the 1960s), coincident with parallel dramatic advances in radiology, microsurgical instrumentation, and anesthesiology. These advances resulted in a better understanding of the pathophysiological aspects and angioarchitecture of the lesions.

Whereas the nomenclature of the lesions in the past was confusing, a new understanding of these diseases that has emerged during the modern era has permitted refinement of the classification of the lesions as distinct biological entities. Modern diagnostic imaging has enabled identification of patients who may benefit from surgical or embolic occlusion, and treatment has become rationally based.

Future progress in the management of spinal vascular lesions may be anticipated, with improvement in noninvasive imaging for early detection of suspected abnormalities. Furthermore, advances in spinal cord neuroprotection may expand the range of future options for surgical or embolic intervention.
Psychological factors in spinal cord stimulation therapy: brief review and discussion
Authors: Doleys Daniel M.
Published: January 2008

✓Since its introduction in 1967 by Shealy and colleagues, spinal cord stimulation (SCS) therapy has become an accepted approach to the treatment of certain types of chronic pain. Significant advances have been made in surgical technique, hardware technology, and the variety of disorders for which SCS has proven to be potentially beneficial. Despite these advancements, 25 to 50% of patients in whom a preimplantation trial screening yields successful results report loss of analgesia within 12 to 24 months of implantation, even in the presence of a functioning device. Psychological factors may play an important role in understanding this observation and improving the outcomes.

In this article the author briefly reviews some of the data on psychological factors potentially involved in SCS. Research on patients with low-back and extremity pain was more heavily relied on because this is the population for which the most data exist. The discussion is divided into four sections: 1) role of psychological factors; 2) psychological screening and assessment; 3) patient selection and psychological screening; and 4) psychological variables and outcomes.

To date, the data remain speculative. Although few definitive conclusions can be drawn, the cumulative existing experience does lend itself to some reasonable recommendations. As with all therapies for chronic pain, invasive or noninvasive, the criteria for success and an acceptable level of failure need to be established, but remain elusive. The emphasis herein is to try to take what works and make it work better.
Mechanisms of spinal cord stimulation in ischemia
Authors: Sagher Oren , Huang Dah-Luen
Published: January 2008

Object

The goal of this study was to assess the duration of neuroprotection after SCS. Nearly 40 years after the first description of spinal cord stimulation (SCS), the mechanisms underlying its physiological effects remain unclear. It is known that SCS affects activity in the nervous system on a broad scale. Local neurohumoral changes within the dorsal horn of the spinal cord have been described, as have changes in cortical activation in a number of brain regions. Spinal cord stimulation has even been found to have profound effects on sympathetic vascular tone, a discovery that has led to its use in ameliorating blood flow in the limbs, heart, and brain.

Methods

In an effort to delineate the limits of neuroprotection offered by SCS, the authors have studied its use in an experimental model of permanent middle cerebral artery (MCA) occlusion in rats. The investigators applied SCS in a delayed fashion 3, 6, or 9 hours after MCA occlusion. The results are reported and mechanisms underlying the physiological effects of SCS are reviewed, with particular attention being paid to the effect of SCS on cerebral blood flow in the setting of cerebral ischemia.

Conclusions

The authors found that SCS applied as late as 6 hours postischemia significantly reduces stroke volumes, whereas SCS applied 9 hours after ischemia fails to reduce stroke injury.
Biomechanics of the posterior lumbar articulating elements
Authors: Serhan Hassan A. , Varnavas Gus , Dooris Andrew P. , Patwardhan Avinash , Tzermiadianos Michael
Published: January 2008

✓The clinical success of lumbar spinal fusion varies considerably, depending on techniques and indications. Although spinal fusion generally helps to eliminate certain types of pain, it may also decrease function by limiting patient mobility. Furthermore, spinal fusion may increase stresses on adjacent nonfused motion segments, accelerating the natural degeneration process at adjacent discs. Additionally, pseudarthrosis, that is, incomplete or ineffective fusion, may result in an absence of pain relief. Finally, the recuperation time after a fusion procedure can be lengthy.

The era of disc replacement is in its third decade, and this procedure has demonstrated promise in relieving back pain through preservation of motion. Total joint replacement with facet arthroplasty of the lumbar spine is a new concept in the field of spinal surgery. The devices used are intended to replace either the entire functional spinal unit (FSU) or just the facets. These devices provide dynamic stabilization for the functional spinal segment as an adjunct to disc replacement or laminectomy and facetectomy performed for neural decompression. The major role of facet replacement is to augment the instabilities created by the surgical decompression or to address chronic instability. Additionally, facet joint replacement devices can be used to replace the painful facet joints, restore stability, and/or to salvage a failed disc or nucleus prosthesis without losing motion.

In this paper the authors review and discuss the role of the lumbar facet joints as part of the three-joint complex and discuss their role in intersegmental motion load transfer and multidirectional flexibility in a lumbar FSU.
Nitinol spring rod dynamic stabilization system and Nitinol memory loops in surgical treatment for lumbar disc disorders: short-term follow up
Authors: Kim Young-Soo , Zhang Ho-Yeol , Moon Byung-Jin , Park Kyung-Woo , Ji Kyu-Yeul , Lee Won-Chang , Oh Kyu-Sung , Ryu Gwon-Ui , Kim Daniel H.
Published: January 2008

Object

The purpose of this study was to analyze the usefulness of the BioFlex, a Nitinol spring rod dynamic stabilization system, and the Nitinol shape memory loop (KIMPF-DI Fixing System) as a posterior dynamic stabilization system in surgery for low-back pain.

Methods

The 103 patients who underwent treatment with the BioFlex system were divided into two groups: Group 1, dynamic stabilization with or without posterior lumbar interbody fusion (PLIF); and Group 2, rigid fixation (PLIF + BioFlex system only). A total of 66 segments were treated with only the BioFlex system; in these the preoperative range of motion (ROM) was 10.0 ± 4.3°, which changed to 4.1 ± 1.9° after surgery. Adjacent-segment ROM changed from 8.4 ± 3.4° to 10.7 ± 3.2° in Group 1 and from 6.5 ± 3.2° to 10.5 ± 4.6° in Group 2 postoperatively. A total of 110 segments received both BioFlex and PLIF, with a fusion rate of 90.0%. The visual analog scale score for back pain improved from 7.3 ± 3.1 to 1.4 ± 1.8 in Group 1 and from 7.4 ± 2.4 to 2.1 ± 2.3 in Group 2. The Oswestry Disability Index improved from 35.2 ± 6.4 to 12.1 ± 4.5 in Group 1 and from 37.8 ± 5.7 to 13.6 ± 4.2 in Group 2. (The ROM and assessment scores expressed are the mean ± standard deviation.)

The 194 patients in whom Nitinol memory loops were implanted were analyzed based on the preoperative and 1-year postoperative ROM of each lumbar segment. The change of ROM in looped segments treated with PLIF was significantly reduced, but the change of ROM in looped segments without PLIF was not significant. The change of ROM at the segment adjacent to the loop was not significant, and the change of kyphosis reflected a slight recovery.

Conclusions

The Nitinol BioFlex dynamic stabilization system can achieve stabilization and simultaneously allow physiological movement, which can in turn decrease the degeneration of adjacent segments. When used with PLIF, the fusion rate can be expected to increase. The flexible Nitinol shape memory loop, a posterior dynamic stabilization device, is an adequate tension band that displays strength similar to the posterior ligamentous structures. In combination with PLIF at the main lesion, the BioFlex system or the Nitinol memory loop can provide posterior dynamic stabilization to the transitional upper or lower segments, enhance the fusion rate, reduce the adjacent-segment degeneration, and provide dynamic stabilization of the spine.