Serum and peritoneal abnormalities in endometriosis: potential use as diagnostic markers.

Endometriosis is an ambiguous disease and its exact pathogenesis still remains elusive to clinicians and scientists. Local and systemic aberrations in immune response are associated with endometriosis. This article reviews the literature regarding various immunological factors such as cytokines, growth factors, adhesion molecules and angiogenic factors involved in the etiopathogenesis of this disease. Our review summarizes the literature regarding biomarkers, which may be reliable nonsurgical tools used in the diagnosis of endometriosis. Superior biomarkers characterized by high sensitivity, specificity and predictive value can help in the early detection and monitoring of disease progression as well as its response to therapeutic treatments critical for its management. A combination predictive model utilizing multiple biomarkers rather then individual markers alone is proposed to improve the diagnostic performance for identifying women with a high likelihood of having endometriosis. Immunomodulators and angiogenic factor blockers have a potential for endometriosis treatment and also to alleviate the pain or infertility associated with the disease. Potential new therapeutic agents include modulators, such as cytokine receptor blockers and angiogenic receptor blockers, presently used for treating endometriosis.

Timing of decompression and fixation after spinal cord injury--when is surgery optimal?

Spinal cord injury affects a large number of young individuals with a significant cost to affected persons, families and societies both in terms of economic and non-economic costs. To date, our interventions have been limited to prevention, good initial resuscitation, modest pharmacotherapy and nursing care. This review examines the role of surgery in spinal cord injury. The pathophysiology of spinal cord injury is reviewed. The compelling animal data for early decompression is discussed as well as evidence for improved neurological outcome with early decompression in humans. Finally, the impact of early surgery on non-neurological outcome and overall complication rates is examined with the concept of "damage control" discussed with relevance to spinal cord injury. It appears that favourable outcomes are achieved with early surgery, with reduced morbidity/mortality, but definitive data is still pending.

Artificial cervical disc replacement: principles, types and techniques.

Cervical arthroplasty after anterior decompression with insertion of a prosthetic total disc replacement has been suggested as an alternate to anterior cervical fusion. Currently there are four cervical arthroplasty devices available on the market whose results in clinical use have been reported. Each device varies in terms of materials, range of motion, insertion technique and constraint. It is not known which device is ideal. Early studies suggest that in the short term, the complication rate and efficacy is no worse than fusion surgery. Long-term results have not yet been reported. This review examines the current prostheses available on the market as well as discussing issues regarding indications and technique. Pitfalls are discussed and early experiences reviewed. In time, it is hoped that a refinement of cervical arthroplasty occurs in terms of both materials and design as well as in terms of indications and clinical outcomes as spinal surgeons enter a new era of the management of cervical spine disease.

Surgical management of spinal epidural abscess: selection of approach based on MRI appearance.

Spinal epidural abscess (SEA) is associated with considerable morbidity and mortality despite its infrequent occurrence. The evolution of magnetic resonance imaging has allowed for easier diagnosis of this potentially devastating condition. It is also possible to predict the intraoperative appearance of each individual case of SEA prior to the procedure, based on the MR findings. Surgical treatment of SEA usually involves extensive decompressive laminectomy, predisposing the patient to the development of spinal instability and deformity. Recent advances in surgical approach to SEA have seen the institution of less invasive techniques to manage this condition, including washout of the epidural space with catheters introduced via laminotomy. Our three cases illustrate the ability to predict the intraoperative findings in patients with SEA, and accordingly adjust the surgical approach to minimize the extensiveness of potentially destabilizing procedures, without impinging on the effectiveness of treatment.

Epidemiology, demographics, and pathophysiology of acute spinal cord injury.

Spinal cord injury occurs through various countries throughout the world with an annual incidence of 15 to 40 cases per million, with the causes of these injuries ranging from motor vehicle accidents and community violence to recreational activities and workplace-related injuries. Survival has improved along with a greater appreciation of patterns of presentation, survival, and complications. Despite much work having been done, the only treatment to date known to ameliorate neurologic dysfunction that occurs at or below the level of neurologic injury has been intravenous methylprednisolone therapy. Much research over the past 30 to 40 years has focused on elucidating the mechanisms of spinal cord injury, with the complex pathophysiologic processes slowly being unraveled. With a greater understanding of both primary and secondary mechanisms of injury, the roles of calcium, free radicals, sodium, excitatory amino acids, vascular mediators, and apoptosis have been elucidated. This review examines the epidemiology, demographics, and pathophysiology of acute spinal cord injury.

The role and timing of decompression in acute spinal cord injury: what do we know? What should we do?

The management of acute spinal cord injury has traditionally concentrated on preventative measures as well as, for the better part of the previous century, conservative care. Pharmacologic interventions, in particular intravenous methylprednisolone therapy, have shown modest improvements in clinical trials and are still undergoing evaluation. More recent interest has focused on the role of surgical reduction and decompression, particularly "early" surgery. A review of the current evidence available in the literature suggests that there is no standard of care regarding the role and timing of surgical decompression. There are insufficient data to support overall treatment standards or guidelines for this topic. There are, however, Class II data indicating that early surgery (<24 hours) may be done safely after acute SCI. Furthermore, there are Class III data to suggest a role for urgent decompression in the setting of 1) bilateral facet dislocation and 2) incomplete spinal cord injury with a neurologically deteriorating patient. Whereas there is biologic evidence from experimental studies in animals that early decompression may improve neurologic recovery after SCI, the relevant time frame in humans remains unclear. To date, the role of decompression in patients with SCI is only supported by Class III and limited Class II evidence and accordingly can be considered only a practice option. Accordingly, there is a strong rationale to undertake prospective, controlled trials to evaluate the role and timing of decompression in acute SCI.

Delayed neurological deterioration following resection of arteriovenous malformations of the brain.

OBJECT: The aim of this study was to analyze delayed neurological deficits following surgical resection of arteriovenous malformations (AVMs). METHODS: The authors report on a consecutive series of 200 patients with angiographically proven AVMs of the brain that were surgically resected between January 1989 and June 1998. The 30-day mortality rate for patients in this series was 1%, with one death caused by AVM resection and one death attributed to basilar artery aneurysm repair following successful AVM resection. The Spetzler-Martin grading system correlated well with the difficulty of surgery. No permanent incidence of morbidity resulted from resection of Grade I or II AVMs; the percentage of patients with a significant neurological deficit due to resection was 7.8% for those with Grade III lesions and 33.3% for those with Grade IV or V AVMs. However, this grading system did not accurately predict the development of delayed neurological deficits. Ten patients (5%) developed delayed neurological deficits after recovering from anesthesia and surgery. The delayed deficit was due to hemorrhage in four of the 10 patients and all four had undergone resection of AVMs measuring at least 4 cm in diameter. An increase in blood pressure during the first 8 postoperative days precipitated hemorrhage in these patients. Edema arising as a consequence of propagated venous thrombosis (two patients) was associated with extensive venous drainage networks rather than large AVM niduses. Both hemorrhagic and edematous complications can be included under the umbrella term of "arterial-capillary-venous hypertensive syndrome" to describe the common underlying pathogenesis accurately. An additional four patients developed a delayed deficit as a result of vasospasm. Vasospasm occurred when resection had involved extensive dissection of proximal anterior and middle cerebral arteries; in such cases the incidence of vasospasm was 27%. CONCLUSIONS: On the basis of their analysis of these complications, the authors recommend strict blood pressure control for patients with lesions measuring 4 cm or more in diameter (particularly those with a deep arterial supply). Thromboprophylaxis with aspirin and heparin is prescribed for patients with extensive venous drainage networks, and prophylactic nimodipine therapy and angiographic surveillance for vasospasm are suggested for patients in whom extensive dissection of proximal anterior or middle cerebral arteries has been necessary.

Combined endovascular stent implantation and endosaccular coil placement for the treatment of a wide-necked vertebral artery aneurysm: technical case report.

OBJECTIVE AND IMPORTANCE: We describe a case in humans of the combined application of endovascular stent placement and Guglielmi detachable coil packing in the management of a wide-necked intracranial aneurysm. CLINICAL PRESENTATION: A 56-year-old woman suffered a subarachnoid hemorrhage secondary to a large wide-necked left vertebral artery aneurysm. Because of the size of the neck of the aneurysm and the extent of its calcification evident on computed tomographic scans, it was deemed unsuitable for surgical intervention or for conventional endovascular coiling. Instead, a combined surgical and endovascular therapy was instituted. INTERVENTION: The left vertebral artery was surgically exposed and cannulated to allow for the placement of an endovascular stent across the neck of the aneurysm to act as a buttress against which Guglielmi detachable coils could be packed. The patient suffered no ill effects as a result of this procedure and made a slow but steady recovery. CONCLUSION: This report describes a case of a wide-necked intracranial artery aneurysm treated using a combination of endovascular stent implantation across an aneurysm neck and endosaccular coil placement to obliterate the aneurysm. The technique described provides another treatment to better manage the difficult entity of wide-necked intracranial aneurysms that may be unsuitable for clipping.

Long-term potentiation saturation in chronic cerebral hypoperfusion.

Chronic reductions in cerebral blood flow (CBF) of between 25 and 50%, in the absence of cerebral infarction, lead to impairments in hippocampal in vitro long-term potentiation (LTP). This study set out to explore some of the properties of this impairment of LTP. LTP is an electrophysiological property known to occur in the hippocampus, a region known to be exquisitely sensitive to hypoxic or ischemic insults. Thus, assessing LTP is a novel way of assessing the effects of subtle ischemic insults. Five male Sprague-Dawley rats had arteriovenous fistulae created surgically in the neck to induce a state of chronic cerebral hypoperfusion (CCH) with the features described above. Five rats were used as age-matched controls. Twenty-six weeks after fistula formation, the animals were prepared for in vitro hippocampal recording in a submerged tissue bath. Extracellular field potentials were recorded at the Schaffer collateral-CA1 region, with a stimulus intensity that achieved a population spike amplitude of 1 mV. After tetanic stimulation, the frequency and magnitude of LTP was compared between control and fistula animals. All animals in both these groups demonstrated LTP in contradistinction to our previous work where LTP was impaired in fistula animals when a higher intensity of stimulation was used. This indicates that the structures that are associated with the initiation and maintenance of LTP (most probably the ischemia-sensitive CA1 pyramidal cells) are saturated as the stimulus intensity is increased. Thus, at this lower intensity of stimulation LTP is preserved in the fistula animals, but found to be impaired as the stimulus intensity is increased. Consequently, this study provides further information on this newly identified subtype of chronic cerebral ischemia which, in time, after further studies in humans, may help to redefine therapeutic indicators for the management of cerebral arteriovenous malformation and severe cerebrovascular disease.

Role of inhibition in chronic cerebral hypoperfusion.

Chronic reductions in cerebral blood flow (CBF) of between 25 and 50% maintained for 26 weeks impair neuronal function, through a mechanism which is not known, but which is now explored. Increased GABAergic synaptic inhibition may play a role, as inhibitory interneurons are known to be relatively resistant to acute ischaemic insults. The phenomenon of tetanus-induced longterm potentiation (LTP) was previously found to be impaired in this setting, and was thus examined in the in vitro rat hippocampus in the presence of bicuculline, a specific GABA(A) antagonist, to evaluate the role of inhibition in the impairment of LTP in chronic cerebral hypoperfusion (CCH). Nine Sprague-Dawley rats aged 8-10 weeks had arteriovenous fistulae (AVF) surgically constructed to reduce CBF to between 25 and 50%. Ten animals were used as age-matched controls. After a further 26 weeks, 400 mum hippocampal slices were prepared. Tetanic stimulation was used in order to attempt to induce LTP. In vitro extracellular field potentials from control and AVF slices with 5 x 10(-)6 M bicuculline exposure and subsequent tetanic stimulation were compared. There was no statistical difference between the responses of the two groups in either scenario (P > 0.05), although LTP was in general more difficult to induce (only occurring in 60% of control animals). Possible causes of this are discussed. It is concluded that increased GABAergic synaptic inhibition does not play a role in impairment of neuronal function seen after 26 weeks of non-infarctional CCH.

Chronic cerebral hypoperfusion inhibits calcium-induced long-term potentiation in rats.

BACKGROUND AND PURPOSE: Long-term potentiation (LTP) in the rat hippocampus induced by tetanic stimulation is impaired by chronic cerebral hypoperfusion. The effects of chronic cerebral hypoperfusion on other forms of LTP are unknown. Such data could help delineate the pathways of cellular alteration caused by chronic cerebral hypoperfusion. The in vitro phenomenon of calcium-induced LTP was thus examined in rat hippocampal CA1 cells that had undergone chronic hypoperfusion with a reduction in cerebral blood flow of between 25% and 50% maintained for 26 weeks. METHODS: Ten Sprague-Dawley rats had a cervical arteriovenous fistula surgically constructed, and an additional 10 animals were used as age-matched controls. Hippocampal slices were prepared after 26 weeks of hypoperfusion, and in vitro extracellular field potential recordings were taken from the Schäffer collateral CA1 region. Properties of LTP induced through transient exposure to a hypercalcemic solution were analyzed. RESULTS: LTP was impaired in animals with an arteriovenous fistula (P < .05). Control animals demonstrated potentiation lasting for the entire 2 hours of recording, whereas fistula animals showed only transient potentiation (< 60 minutes) before returning to baseline values. CONCLUSIONS: Calcium-induced LTP is impaired by chronic cerebral hypoperfusion. This form of LTP is different from that induced by tetanic stimulation. It is the most sensitive test available for in vitro detection of the changes induced in neuronal function by chronic noninfarctional reductions in cerebral blood flow of 25% to 50% and may indicate that the most basic cellular parameters involving calcium homeostasis and metabolism are being altered. The precise mechanisms remain to be elucidated, and several postulates are discussed.

Normal perfusion pressure breakthrough: the role of capillaries.

Excision of human cerebral arteriovenous malformations (AVMs) can be complicated by postoperative edema and hemorrhage in adjacent brain tissue, despite the complete excision of the malformation. Various theories have purported to explain the hemodynamic basis for this predisposition, including disordered autoregulation causing "normal perfusion pressure breakthrough" and obstruction of venous drainage leading to "occlusive hyperemia." This study did not evaluate the arterial or venous circulations in this scenario, but rather examined the capillaries in adjacent brain parenchyma for any structural deficiencies that would predispose the brain to the postoperative formation of edema and hemorrhage. Arteriovenous fistulas (AVFs) were created surgically in the necks of 10 male Sprague-Dawley rats, which caused chronic cerebral hypoperfusion with a reduction in cerebral blood flow of between 25% and 50%. Ten age-matched animals were used as controls. Twenty-six weeks after AVF formation the animals were killed and perfusion fixed. Their brain tissue was prepared for light microscopic studies by staining for glial fibrillary acidic protein or for transmission electron microscopy. In the CA1 pyramidal cell region of the hippocampus, it was found that in the animals with AVFs there was increased capillary density and absent astrocytic foot processes in some of these vessels. It was concluded that these vessels had developed as a result of neovascularization in response to chronic cerebral ischemia and that their anatomical configuration made them prone to mechanical weakness and instability following the increase in perfusion pressure that occurs in adjacent brain parenchyma after AVM excision. The authors believe that this study pinpoints a structural accompaniment to the hemodynamic changes that occur in brain tissue in the vicinity of cerebral AVMs that predispose these areas to the formation of edema and hemorrhage after AVM excision.

Chronic cerebral hypoperfusion: pathological and behavioral consequences.

OBJECTIVE: Although the effects of acute ischemic insults to the brain are well known, the effects related to chronic ischemia are poorly delineated. The pathological and behavioral changes induced by a chronic noninfarctional reduction in cerebral blood flow of 25 to 50% maintained for 6 months were assessed. METHODS: In each of 18 male Sprague-Dawley rats, an arteriovenous fistula was created in the neck via an anastomosis between the right external jugular vein and the right common carotid artery to induce cerebral hypoperfusion. Nineteen age-matched animals comprised a control group. Six months after surgery, the animals were examined using light and electron microscopic techniques, as well as via a battery of behavioral tests (motor, open field, and T-maze). RESULTS: Examination of the hippocampus by using light microscopy revealed disorganization of the CA1 sector with an increased number of astrocytes. Transmission electron microscopy of the CA1 region demonstrated neurons with increased lipofuscin pigment and central nucleoli and astrocytes with more numerous cytosolic mitochondria. Motor performance testing revealed no gross motor deficits, although open-field assessment demonstrated increased exploratory behavior in rats with fistulas. Finally, T-maze testing results suggested that errors in working memory were more common in rats undergoing chronic cerebral hypoperfusion (P < 0.05). CONCLUSIONS: These findings suggest that chronic reductions in cerebral blood flow of a magnitude previously thought to be harmless to neurons (i.e., reduced by 25-50%) do alter neuronal structure and affect whole animal behavior. Such a scenario may be responsible for a symptomatology secondary to arteriovenous steal and severe carotid stenoses. The mechanisms are still unknown.