Hippocampal tissue of patients with refractory temporal lobe epilepsy is associated with astrocyte activation, inflammation, and altered expression of channels and receptors.

Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy. Previous research has demonstrated several trends in human tissue that, undoubtedly, contribute to the development and progression of TLE. In this study we examined resected human hippocampus tissue for a variety of changes including gliosis that might contribute to the development and presentation of TLE. The study subjects consisted of six TLE patients and three sudden-death controls. Clinicopathological characteristics were evaluated by H&E staining. Immunohistological staining and Western blotting methods were used to analyze the samples. Neuronal hypertrophy was observed in resected epileptic tissue. Immunohistological staining demonstrated that activation of astrocytes was significantly increased in epileptic tissue as compared to corresponding regions of the control group. The Western blot data also showed increased CX43 and AQP4 in the hippocampus and downregulation of Kir4.1, α-syntrophin, and dystrophin, the key constituents of AQP4 multi-molecular complex. These tissues also demonstrated changes in inflammatory factors (COX-2, TGF-ß, NF-κB) suggesting that these molecules may play an important role in TLE pathogenesis. In addition we detected increases in metabotropic glutamate receptor (mGluR) 2/3, mGluR5 and kainic acid receptor subunits KA1 (Grik4) and KA2 (Grik5) in patients' hippocampi. We noted increased expression of the α1c subunit comprising class C L-type Ca(2+) channels and calpain expression in these tissues, suggesting that these subunits might have an integral role in TLE pathogenesis. These changes found in the resected tissue suggest that they may contribute to TLE and that the kainic acid receptor (KAR) and deregulation of GluR2 receptor may play an important role in TLE development and disease course. This study identifies alterations in number of commonly studied molecular targets associated with astrogliosis, cellular hypertrophy, water homeostasis, inflammation, and modulation of excitatory neurotransmission in hippocampal tissues from TLE patients.

Neuronal hypertrophy in the neocortex of patients with temporal lobe epilepsy.

The underlying cause of neocortical involvement in temporal lobe epilepsy (TLE) remains a fundamental and unanswered question. Magnetic resonance imaging has shown a significant loss in temporal lobe volume, and it has been proposed that neocortical circuits are disturbed functionally because neurons are lost. The present study used design-based stereology to estimate the volume and cell number of Brodmann's area 38, a region commonly resected in anterior temporal lobectomy. Studies were conducted on the neocortex of patients with or without hippocampal sclerosis (HS). Results provide the surprising finding that TLE patients have significant atrophy of neocortical gray matter but no loss of neurons. Neurons are also significantly larger, dendritic trees appear sparser, and spine density is noticeably reduced in TLE specimens compared with controls. The increase in neuronal density we found in TLE patients is therefore attributable to large neurons occupying a much smaller volume than in normal brain. Neurons in the underlying white matter are also increased in size but, in contrast to other reports, are not significantly elevated in number or density. Neuronal hypertrophy affects HS and non-HS brains similarly. The reduction in neuropil and its associated elements therefore appears to be a primary feature of TLE, which is not secondary to cell loss. In both gray and white matter, neuronal hypertrophy means more perikaryal surface area is exposed for synaptic contacts and emerges as a hallmark of this disease.

Predictors of successful extubation in neurosurgical patients.

A respiratory therapist-driven weaning protocol incorporating daily screens, spontaneous breathing trials (SBT), and prompts to caregivers has been associated with superior outcomes in mechanically ventilated medical patients. To determine the effectiveness of this approach in neurosurgical (NSY) patients, we conducted a randomized controlled trial involving 100 patients over a 14-mo period. All had daily screens of weaning parameters. If these were passed, a 2-h SBT was performed in the Intervention group. Study physicians communicated positive SBT results, and the decision to extubate was made by the primary NSY team. Patients in the Intervention (n = 49) and Control (n = 51) groups had similar demographic characteristics, illness severity, and neurologic injuries. Among all patients, 87 (45 in the Control and 42 in the Intervention group) passed at least one daily screen. Forty (82%) patients in the Intervention group passed SBT, but a median of 2 d passed before attempted extubation, primarily because of concerns about the patient's sensorium (84%). Of 167 successful SBT, 126 (75%) did not lead to attempted extubation on the same day. The median time of mechanical ventilation was 6 d in both study groups, and there were no differences in outcomes. Overall complications included death (36%), reintubation (16%), and pneumonia (9%). Tracheostomies were created in 29% of patients. Multivariate analysis showed that Glasgow Coma Scale (GCS) score (p < 0.0001) and partial pressure of arterial oxygen/fraction of inspired oxygen ratio (p < 0.0001) were associated with extubation success. The odds of successful extubation increased by 39% with each GCS score increment. A GCS score > or = 8 at extubation was associated with success in 75% of cases, versus 33% for a GCS score < 8 (p < 0.0001). Implementation of a weaning protocol based on traditional respiratory physiologic parameters had practical limitations in NSY patients, owing to concerns about neurologic impairment. Whether protocols combining respiratory parameters with neurologic measures lead to superior outcomes in this population requires further investigation.

Rheolytic catheter and thrombolysis of dural venous sinus thrombosis: a case series.

OBJECTIVE: The high morbidity and mortality rates associated with dural sinus thrombosis may be heightened by a delay in diagnosis, which necessitates prompt and effective treatment. Traditional treatment consists of the initiation of systemic anticoagulation with heparin and, more recently, regional thrombolysis with direct endovascular infusion of thrombolytic agents. We report our experience in a series of five patients in whom we accomplished mechanical clot lysis with the combination of a rheolytic device and balloon catheters. METHODS: Five patients with dural sinus thrombosis were treated with a combination of pharmacological and mechanical thrombolysis with the 5-French Angiolet rheolytic catheter (Possis Medical, Minneapolis, MN) and balloon catheters. The success of the procedure was determined by resolution of or improvement in the patient's neurological examination results and imaging features. RESULTS: All five patients demonstrated immediate improvement as observed on imaging studies or in terms of neurological status. Three patients required more than one intervention, and all but one patient continued to improve after the final intervention. Two of the five patients continued to experience mild residual neurological deficits, and two patients experienced complete recovery. The fifth patient had a delayed recurrence of thrombosis that required multiple interventions, and the patient has significant neurological deficits. Navigation of the dural sinuses was possible in all patients with the use of a microcatheter and was possible to a variable degree with the rheolytic catheter. Known complications of the procedures included two pseudoaneurysms at the femoral puncture site. CONCLUSION: Mechanical clot lysis is a powerful technique for immediate restoration of antegrade venous flow in dural sinus thrombosis. In most patients, the superior sagittal sinuses and contralateral transverse sinuses could be accessed with the 5-French rheolytic catheter.

Metabolic acidosis, rhabdomyolysis, and cardiovascular collapse after prolonged propofol infusion.

The authors present the hospital course of a 13-year-old girl with a closed head injury who received a prolonged infusion of propofol for sedation and, subsequently, died as a result of severe metabolic acidosis, rhabdomyolysis, and cardiovascular collapse. The patient had been treated for 4 days at a referring hospital for a severe closed head injury sustained in a fall from a bicycle. During treatment for elevations of intracranial pressure, she received a continuous propofol infusion (100 microg/kg/min). The patient began to exhibit severe high anion gap/low lactate metabolic acidosis, and was transferred to the pediatric intensive care unit at the authors' institution. On arrival there, the patient's Glasgow Coma Scale score was 3 and this remained unchanged during her brief stay. The severe metabolic acidosis was unresponsive to maximum therapy. Acute renal failure ensued as a result of rhabdomyolysis, and myocardial dysfunction with bizarre, wide QRS complexes developed without hyperkalemia. The patient died of myocardial collapse with severe metabolic acidosis and multisystem organ failure (involving renal, hepatic, and cardiac systems) approximately 15 hours after admission to the authors' institution. This patient represents another case of severe metabolic acidosis, rhabdomyolysis, and cardiovascular collapse observed after a prolonged propofol infusion in a pediatric patient. The authors suggest selection of other pharmacological agents for long-term sedation in pediatric patients.

Angiotensin-converting enzyme expression in human carotid artery atherosclerosis.

Angiotensin-converting enzyme (ACE) inhibitors reduce the progression of atherosclerosis in animal models and reinfarction rates after myocardial infarction in humans. Although expression of components of the renin-angiotensin system has been reported in human coronary arteries, no data regarding their presence in carotid arteries, a frequent site for the occurrence of atherosclerosis plaques, are available. The following study sought to determine whether ACE mRNA and protein can be detected in human carotid atheromatous lesions. Twenty-four intact endarterectomy specimens were obtained from patients with severe carotid occlusive disease (17 males and 7 females, aged 68+/-1 years) and fixed within 30 minutes. Carotid artery specimens contained advanced Stary type V and VI lesions, and human ACE mRNA expression and protein were localized in cross sections by the combination of in situ hybridization and immunohistochemistry. Cell type-specific antibodies were used to colocalize ACE to smooth muscle cells, endothelial cells, macrophages, or lymphocytes. ACE protein was localized in the intima, whereas the overlying media was largely free of ACE staining. In less complicated lesions, ACE staining was modest and could be visualized in scattered clusters of macrophages and on the luminal side of carotid artery vascular endothelium. Smooth muscle cells were largely negative. ACE staining increased as lesions became more complex and was most prominent in macrophage-rich regions. The shoulder regions of plaques contained numerous ACE-positive macrophage foam cells and lymphocytes. In these areas, microvessels were positive for endothelial cell and smooth muscle cell ACE expression. However, microvessels in plaques free of inflammatory cells were stained only faintly for ACE expression. Labeling for ACE mRNA mirrored the pattern of protein expression, localizing ACE mRNA to macrophages and microvessels within the intima. In conclusion, atherosclerosis alters carotid artery ACE production, increasing transcription and translation within regions of plaque inflammation. These data provide another important mechanism by which inflammation associated with increased ACE expression may contribute to the progression of atherosclerosis.

Fibrosarcoma of the sacrum in a child: management by sacral resection and reconstruction.

We describe the diagnosis and surgical management of fibrosarcoma of the sacrum in a pediatric patient. We retrospectively reviewed the literature and a case report. Total sacrectomy is a viable treatment option in the management of large malignant sacral tumors. The techniques used in adult patients can be extended to and improved upon for pediatric patients. The input of multiple surgical specialties is essential in the management of these lesions.

Editing status at the Q/R site of the GluR2 and GluR6 glutamate receptor subunits in the surgically excised hippocampus of patients with refractory epilepsy.

The editing status of mRNA at the Q/R site of the glutamate receptor subunits GluR2 and GluR6 modulates channel conductivity and ion selectivity of ionotropic AMPA/KA receptors. Alteration of the editing process may be involved in the debilitating effects of epilepsy. The ratio of unedited/edited (Q/R) forms of GluR2 and GluR6 subunits was examined in conjunction with the expression of two double-stranded RNA-specific adenosine deaminases (DRADA) in surgically excised hippocampus from patients with refractory epilepsy compared with that of control samples. In the majority of patients with long histories of epilepsy, the GluR2 transcript was detected in the completely edited form, however, in two (out of 16 tested) hippocampal samples of young subjects (2 and 10 years old) we were able to identify the unedited transcript of GluR2 subunit. The proportion of unedited fraction of GluR6(Q) subunit was decreased to 9% compared to control human hippocampus. We conclude that the editing process in epileptic specimens is selectively affected by seizure activity in the epileptic focus.

Construction and characterization of nitrate reductase-based amperometric electrode and nitrate assay of fertilizers and drinking water.

The construction and characterization of a nitrate reductase-based amperometric electrode for determination of nitrate ion is described. The electrode consisted of nitrate reductase held by dialysis membrane onto a Nafion-coated glassy carbon electrode. Methyl viologen was allowed to absorb into the Nafion layer, which acted as a reservoir for the electron mediator. The utility of the electrode to assay fertilizer and water sample for nitrate was demonstrated. The assays conducted with this electrode compared well with colorimetric and potentiometric assays of the same samples.

Sinus pericranii.

Sinus pericranii is an anomalous extracranial vascular malformation that is in continuity with the intracranial dural venous sinuses. Five case reports, three congenital and two traumatic, are described. Clinical management, including evaluation, diagnosis, and treatment, is discussed. Awareness of this entity by plastic surgeons will allow for earlier diagnosis and appropriate surgical management, resulting in decreased risk of complications.

Development of skills for coping with arthritis: an innovative group approach.

Innovative group sessions were initiated in 1990 to address the psychosocial needs of clients with arthritis. In our unique approach, the facilitator, in each session, reads aloud a journal describing an aspect of living with arthritis. These journals are powerful tools that foster the process of learning to cope. Members experience normalization of their feelings, as well as reduced isolation. Improved coping skills are thereby developed. The topics include: Credibility, Living with Unpredictability, Living in Fear, Living with Chronic Pain, Living with Loss, Anger and Depression, Relationships and Sexuality, and Coping Strategies. These innovative methods are more efficient and can have a far stronger impact than individual counselling. Groups have taken place in community settings, but could be adapted to hospital settings.

Isolated straight sinus and deep cerebral venous thrombosis: successful treatment with local infusion of urokinase. Case report.

A 23-year-old woman presented with headache and progressive lethargy. The diagnosis of isolated thrombosis of the straight sinus and of the deep cerebral venous system was established using cranial computerized tomography, magnetic resonance imaging, phase-contrast magnetic resonance venography, and cerebral angiography. Because of the rapid deterioration in the patient's clinical condition, the authors used direct transcatheter infusion of urokinase into the straight sinus. This treatment resulted in a successful outcome.

Changes in glutamate receptor subunit composition in hippocampus and cortex in patients with refractory epilepsy.

An assessment of glutamate receptor subunit profiles was made in hippocampus and temporal lobe cortex of patients with refractory epilepsy. Molecular biological analyses using reverse transcription reaction (RT) followed by polymerase chain reaction (PCR) revealed changes in the distribution profile of the transcripts of AMPA/KA glutamate receptor subunits in hippocampal and cortical tissue from patients with refractory epilepsy when compared to similar tissue from six human and four non-human primate samples with no history of seizures or seizure medication. A severe mean decrease (38% of control) in mRNA for the GluR1 subunit was found in 400 mm cross-sections of hippocampus from patients with epilepsy. Less severe but significant reductions in that GluR1 subunit expression (54% of control) were exhibited in samples of excised temporal pole cortex from the same subjects. Message for the GluR4 subunit was also significantly decreased in hippocampus (68% of control), but in contrast to GluR1, GluR4 mRNA level was not decreased in temporal cortex. Levels of GluR2 mRNA were not significantly changed in epileptic hippocampal and cortical tissue relative to control samples. Protein levels of the GluR1 and GluR4 subunits quantified by Western blot analysis were also reduced in hippocampal and cortical tissue from epilepsy patients. Two other kainate subunit transcripts, GluR6 and KA1 also showed significant changes compared to non-epileptic tissue (136% and 71% of control, respectively). Results are discussed in terms of possible mechanisms by which protracted seizures could produce selective loss of certain AMPA/KA subunits.

Extracerebral cavernous angiomas of the cavernous sinus in the middle fossa.

UNLABELLED: Intracranial extracerebral cavernous angiomas (ECCAs) share the same histologic features as intracerebral lesions, but their clinical picture is different. Surgical treatment of ECCAs of the cavernous sinus remains a challenge for the neurosurgeon because of a high mortality and morbidity due to uncontrollable and massive hemorrhage. METHODS: We have experienced seven patients with ECCAs of the cavernous sinus between 1982 and 1994. All cases were verified histologically during surgery and two were totally resected during the first surgical attempt. Six of seven patients were female. The mean age at diagnosis was 54.5 years (range; 43 to 71 years). RESULTS: Computed tomography showed a round or dumbbell-shaped mass in the area of the cavernous sinus. Magnetic resonance imaging revealed a low to isointense mass lesion on the T1-weighted image. Only one of our patients showed a minimal amount of vascular staining on angiography. The total excision of these malformations was difficult because intraoperative bleeding could be profuse. In one case, radiation therapy induced a reduction in the size of the tumor after failure of surgical removal. CONCLUSIONS: In planning surgical strategy for ECCAs, care should be taken to control the massive bleeding. Radiation therapy is helpful to suppress the tumor growth.

Comparative results of transluminal extraction coronary atherectomy in saphenous vein graft lesions with and without thrombus.

OBJECTIVES: The purpose of this retrospective study was to compare the results of transluminal extraction coronary atherectomy in saphenous vein graft lesions with and without angiographic thrombus. BACKGROUND: Percutaneous interventions in lesions with thrombus are associated with reduced procedural success and increased risk of complications. Use of the transluminal extraction catheter, which cuts and aspirates atheroma and thrombus, has been advocated as a potential revascularization strategy for lesions with thrombus. METHODS: Baseline patient characteristics, lesion morphology, immediate angiographic results, in-hospital complications and follow-up were prospectively entered into an interventional cardiology data base. The results of transluminal extraction coronary atherectomy in saphenous vein bypass grafts with angiographic thrombus were compared with results in similar grafts without angiographic thrombus. RESULTS: Transluminal extraction coronary atherectomy was performed in 175 patients with 183 vein graft lesions, including 59 lesions (32%) with thrombus (Group 1) and 124 (68%) without thrombus (Group 2). Compared with lesions in Group 2, lesions in Group 1 were associated with a higher incidence of baseline total occlusion, diffuse disease and abnormal Thrombolysis in Myocardial Infarction (TIMI) grade flow (p < 0.05); more severe diameter stenosis at baseline, after atherectomy and after final angiography (p < 0.05); a lower rate of clinical success (69% vs. 88%, p < 0.01); and more angiographic and clinical complications, including no reflow (p < 0.05), vascular repair (p < 0.05) and Q wave myocardial infarction (p = 0.09). CONCLUSIONS: In transluminal extraction coronary atherectomy of saphenous vein bypass grafts, the presence of thrombus is associated with more baseline lesion complexity, reduced clinical success and increased risk of no reflow, Q wave myocardial infarction and vascular repair.

Features and outcome of no-reflow after percutaneous coronary intervention.

No-reflow is an uncommon complication that may occur after revascularization of patients with acute myocardial infarction, after interventions in saphenous vein bypass grafts, and after the use of some new interventional devices. However, the clinical impact of no-reflow after coronary intervention is unknown. Accordingly, this study examined the incidence, clinical presentation, angiographic characteristics, and outcome of no-reflow after percutaneous coronary intervention. No-reflow was defined as an acute reduction in antegrade flow (< or = 1, as defined by the Thrombolysis in Myocardial Infarction [TIMI] trial) not attributable to abrupt closure, high-grade stenosis, or spasm of the original target lesion. Among 10,676 coronary interventions performed between October 1988 and June 1993, no-reflow occurred in 66 patients (0.6%). These patients were compared with a subgroup of 500 consecutive patients who did not exhibit no-reflow. The incidence of no-reflow was 30 of 9,431 (0.3%) for percutaneous transluminal coronary angioplasty, 1 of 317 (0.3%) for excimer laser, 8 of 104 (7.7%) for Rotablator (Heart Technologies, Bellevue, Washington), 21 of 469 (4.5%) for extraction atherectomy, and 6 of 355 (1.7%) for directional atherectomy. Compared with those without no-reflow, patients with no-reflow experienced a 10-fold higher incidence of in-hospital death (15%) and acute myocardial infarction (31%). Correlates of in-hospital mortality included acute myocardial infarction on presentation (p = 0.006) and final flow < 3 (as defined by the TIMI trial) at completion of the procedure (p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Randomized prospective evaluation of prolonged versus abbreviated intravenous heparin therapy after coronary angioplasty.

OBJECTIVES: This study was designed to prospectively evaluate the routine use of continuous heparin therapy after successful uncomplicated coronary angioplasty. BACKGROUND: The use of such therapy varies among institutions and may increase the incidence of complications. Evaluation of the risks and benefits of abbreviated heparin therapy combined with early sheath removal after coronary angioplasty is necessary to determine optimal postprocedure care. METHODS: We prospectively studied 284 patients who were scheduled for elective coronary angioplasty. Historical, clinical, physiologic and angiographic data were gathered. All patients received an initial bolus of heparin and then were randomized during the procedure to receive either no additional heparin therapy or an adjusted 24-h infusion. On the basis of specific criteria, additional heparin was not withheld if procedural results suggested an increased risk for complications. RESULTS: Two hundred thirty-eight patients completed the study; 46 others were excluded in the catheterization laboratory because of unfavorable procedural results. The patients with abbreviated (n = 118) and 24-h (n = 120) therapy did not differ with respect to demographic and angiographic findings. However, the former had fewer bleeding complications (0% vs. 7%, p < 0.001) and were discharged earlier (mean +/- SD 23 +/- 11 h vs. 42 +/- 24 h, p < 0.001). One patient in this group had a major complication shortly after angioplasty. The mean savings in hospital charges in the abbreviated therapy group was $1,370 ($6,093 +/- $1,772 vs. $7,463 +/- $1,782, p < 0.001). CONCLUSIONS: Omission of routine heparin therapy after successful coronary angioplasty reduces bleeding complications without increasing patient risk. Earlier discharge and significant cost savings are possible under proper conditions.

Induction of ischemic tolerance following brief focal ischemia in rat brain.

The objective of this study was to determine whether brief focal ischemia induces ischemic tolerance in rat brain. Focal ischemia was produced in Wistar rats by occluding the middle cerebral artery (MCA) for 20 min at a distal site. Following recovery for 24 h, the animals were subjected to a 10-min episode of forebrain ischemia using a combination of bilateral carotid artery occlusion and systemic hypotension. Histologic injury, assessed after a survival period of 3-4 days, consisted of selective neuronal necrosis bilaterally in cerebral cortex, striatum, hippocampus, and thalamus superimposed upon a small cortical infarct adjacent to the site of MCA occlusion. However, the intensity of neuronal necrosis in the MCA territory of the neocortex ipsilateral to MCA occlusion was markedly less than that in the contralateral MCA cortex. In contrast, the extent of neuronal necrosis in subcortical structures was similar in both hemispheres. Unexpectedly, animals in which the MCA was manipulated, but not occluded, also exhibited a marked reduction of neuronal necrosis in the ipsilateral MCA neocortex following forebrain ischemia. However, in animals with craniotomy alone, forebrain ischemia caused a similar extent of neuronal necrosis in the MCA neocortex of both hemispheres. Transient occlusion of the MCA induced the focal expression of the 72-kDa heat-shock protein (hsp72) in the MCA territory of the neocortex. Limited expression of hsp72 was also detected following sham occlusion, but not after craniotomy alone. These results demonstrate focal induction of ischemic tolerance in rat neocortex that may be related to expression of heat-shock proteins.