Reactive oxygen species in status epilepticus.

There has been growing evidence for a critical role of oxidative stress in neurodegenerative disease, providing novel targets for disease modifying treatments. Although antioxidants have been suggested and tried in the treatment of epilepsy, it is only recently that the pivotal role of oxidative stress in the pathophysiology of status epilepticus has been recognized. Although conventionally thought to be generated by mitochondria, reactive oxygen species during status epilepticus and prolonged seizure are generated mainly by NADPH (nicotinamide adenine dinucleotide phosphate) oxidase (stimulated by NMDA receptor activation). Excessive production of reactive oxygen species results in lipid peroxidation, DNA damage, enzyme inhibition, and mitochondrial damage, culminating in neuronal death. Antioxidant therapy has been hampered by poor CNS penetration and rapid consumption by oxidants. However, alternative approaches such as inhibiting NADPH oxidase or increasing endogenous antioxidant defenses through activation of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) could avoid these problems. Small molecules that increase Nrf2 activation have proven to be not only effective neuroprotectants following status epilepticus, but also potently antiepileptogenic. There are "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".

[Update on anti-N-methyl-D-aspartate receptor encephalitis]. / Update Anti-N-Methyl-D-Aspartat-Rezeptor-Enzephalitis.

Autoimmune encephalitis is a group of autoimmune inflammatory disorders affecting both grey and white matter of the central nervous system. Encephalitis with autoantibodies against the N­methyl-D-aspartate receptor (NMDA-R) is the most frequent autoimmune encephalitis syndrome presenting with a characteristic sequence of psychiatric and neurological symptoms. Treatment necessitates a close interdisciplinary cooperation. This article provides an update on the current knowledge on diagnostic standards, pathogenesis, and treatment strategies for anti-NMDA-R encephalitis from psychiatric and neurological perspectives.

Route of hysterectomy: an evidence-based approach.

The number of hysterectomies performed has long been a concern; now the appropriateness of the surgical method is under more careful scrutiny. What is the clinically appropriate route and method for hysterectomy in a given patient? To ensure that each patient receives the best possible care at reasonable costs, physicians must closely examine recent data comparing surgical approaches to hysterectomy. So, what is the most evidence-based approach for hysterectomy?

Intravenous levetiracetam: a new treatment alternative for refractory status epilepticus.

The purpose of this study was to investigate the safety and efficacy of intravenous levetiracetam (LEV-iv) in refractory status epilepticus (SE). A retrospective chart review was performed on patients who received LEV-iv for treatment of SE (n = 36) and had failed at least one other antiepileptic drug. LEV-iv (median 3000 mg/day; range 1000-9000) was administered as a bolus loading (500-2000 mg per 30-60 min, n = 30) or as a continuous pump infusion (n = 6). SE was terminated in 69% ("responders"); 31% ("non-responders") remained in SE. Factors associated with failure were: dose escalation over 3000 mg/day, lack of bolus loading, treatment latency over 48 h, age over 80 years, non-convulsive SE with coma ("subtle SE"), periodic lateralised epileptiform discharges (PLEDs) on EEG, acute cerebral lesion and intubation narcosis. SE was terminated in all eight patients without brain lesion (p = 0.033), and in all seven patients with complex partial SE (p = 0.051). Outcome was favourable (ambulatory patients) in 48% (responders) compared with 0% (non-responders), and "adverse" (death or continuing coma/stupor) in 24% (responders) compared with 100% (non-responders). Mortality was 17% (responders 4%, non-responders 45%). No patient had cardiocirculatory side effects or worsening of SE. Two patients experienced nausea and vomiting during LEV-iv loading, leading to aspiration pneumonia in one. This study suggests that LEV-iv may be a safe and efficacious treatment of SE. Prospective and controlled trials are imperative to confirm these preliminary findings.

Memory performance is related to language dominance as determined by the intracarotid amobarbital procedure.

OBJECTIVE: The goal of this study was to explore the relationship between language and memory lateralization in patients with epilepsy undergoing the intracarotid amobarbital procedure. METHODS: In 386 patients, language lateralization and memory lateralization as determined by laterality index (LI) were correlated with each other. RESULTS: Language lateralization and memory lateralization were positively correlated (r=0.34, P<0.01). Correlations differed depending on the presence and type of lesion (chi(2)=7.98, P<0.05). LIs correlated significantly higher (z=2.82, P<0.05) in patients with cortical dysplasia (n=41, r=0.61, P<0.01) compared with the group without lesions (n=90, r=0.16, P>0.05), with patients with hippocampal sclerosis falling between these two groups. Both memory (P<0.01) and language (P<0.01) LIs were higher in right- compared with left-sided lesions. CONCLUSION: Correlation of language and memory is more pronounced in patients with structural lesions as compared with patients without lesions on MRI.

Different regional neuroinhibitory effects of adenosine on stimulus-induced patterns of bioelectric activity of rat hippocampal and neocortical tissues.

Adenosine is an inhibitory modulator of brain activity with neuroprotective and anticonvulsant properties. To investigate the distribution of bioelectric activities under application of adenosine, rat hippocampal and neocortical slices were incubated with the voltage-sensitive dye RH795 and neuronal activity was monitored using a fast-imaging photodiode array combined with standard field potential recordings. The effects of adenosine (1-50 micromol/l) on the spatial distribution of stimulus-induced activities were studied in non-epileptiform as well as epileptiform conditions. Epileptiform activity was induced by omission of Mg(2+) from the bath medium. The adenosine's inhibitory effects on the amplitude and spatial extent of stimulus-induced bioelectric activity in the hippocampus were most prominent in strata radiatum and pyramidale in both control and epileptic mediums. Adenosine's inhibitory actions were different on various layers of neocortical tissues in non-epileptiform and epileptiform conditions. Layers II and III showed the most inhibition by application of adenosine in control slices. In epileptiform medium, however, adenosine exerts significant suppressive effects only in layer I of neocortical slices. The data demonstrate a region-specific modulatory potential of adenosine on neuronal network excitability in the hippocampus and neocortex. This may be important in local adenosine therapy in epilepsy.

Frequency of seizures and epilepsy in neurological HIV-infected patients.

BACKGROUND: Infection with the human immunodeficiency virus (HIV) is associated both with infections of the central nervous system and with neurological deficits due to direct effects of the neurotropic virus. Seizures and epilepsy are not rare among HIV-infected patients. We investigated the frequency of acute seizures and epilepsy of patients in different stages of HIV infection. In addition, we compared the characteristics of patients who experienced provoked seizures only with those of patients who developed epilepsy. METHODS: The database of the Department of Neurology, University of Münster, was searched for patients with HIV infection admitted between 1992 and 2004. Their charts were reviewed regarding all available sociodemographic, clinical, neurophysiological, imaging and laboratory data, therapy and outcome. Stage of infection according to the CDC classification and the epileptogenic zone were determined. RESULTS: Of 831 HIV-infected patients treated in our department, 51 (6.1%) had seizures or epilepsy. Three of the 51 patients (6%) were diagnosed with epilepsy before the onset of the HIV infection. Fourteen patients (27%) only had single or few provoked seizures in the setting of acute cerebral disorders (eight patients), drug withdrawal or sleep withdrawal (two patients), or of unknown cause (four patients). Thirty-four patients (67%) developed epilepsy in the course of their HIV infection. Toxoplasmosis (seven patients), progressive multifocal leukencephalopathy (seven patients) and other acute or subacute cerebral infections (five patients) were the most frequent causes of seizures. EEG data of 38 patients were available. EEG showed generalized and diffuse slowing only in 9 patients, regional slowing in 14 patients and regional slowing and epileptiform discharges in 1 patient. Only 14 of the patients had normal EEG. At the last contact, the majority of the patients (46 patients=90%) were on highly active antiretroviral therapy (HAART). Twenty-seven patients (53%) were on anticonvulsant therapy (gabapentin: 14 patients, carbamazepine: 9 patients, valproate: 2 patients, phenytoin: 1 patient, lamotrigine: 1 patient). Patients with only provoked seizures had no epilepsy risk factors except HIV infection, and were less likely to be infected via intravenous drug abuse. CONCLUSIONS: Seizures are a relevant neurological symptom during the course of HIV infection. Although in some patients seizures only occur provoked by acute disease processes, the majority of patients with new onset seizures eventually develops epilepsy and require anticonvulsant therapy. Intravenous drug abuse and the presence of non-HIV-associated risk factors for epilepsy seem to be associated with the development of chronic seizures in this patient group.

Long-term survival of a cemented titanium-aluminium-vanadium alloy straight-stem femoral component.

We present a retrospective series of 170 cemented titanium straight-stem femoral components combined with two types of femoral head: cobalt-chromium (CoCr) alloy (114 heads) and alumina ceramic (50 heads). Of the study group, 55 patients (55 stems) had died and six (six stems) were lost to follow-up. At a mean of 13.1 years (3 to 15.3) 26 stems had been revised for aseptic loosening. The mean follow-up time for stable stems was 15.1 years (12.1 to 16.6). Survival of the stem at 15 years was 75.4% (95% confidence interval (CI) 67.3 to 83.5) with aseptic failure (including radiological failure) as the end-point, irrespective of the nature of the head and the quality of the cement mantle. Survival of the stem at 15 years was 79.1% (95% CI 69.8 to 88.4) and 67.1% (95% CI 51.3 to 82.9) with the CoCr alloy and ceramic heads, respectively. The quality of the cement mantle was graded as a function of stem coverage: stems with complete tip coverage (type 1) had an 84.9% (95% CI 77.6 to 92.2) survival at 15 years, compared with those with a poor tip coverage (type 2) which had a survival of only 22.4% (95% CI 2.4 to 42.4). The poor quality of the cement mantle and the implantation of an alumina head substantially lowered the survival of the stem. In our opinion, further use of the cemented titanium alloy straight-stem femoral components used in our series is undesirable.

Status epilepticus results in persistent overproduction of reactive oxygen species, inhibition of which is neuroprotective.

Epilepsy and seizure activity result in the generation of reactive oxygen species (ROS), which contribute to seizure-induced neuronal damage. Recent in vitro evidence indicates that NADPH oxidase contributes significantly to seizure-induced ROS. We further tested this in rat glio-neuronal cultures and in ex vivo chronic epileptic rat brain tissue using live cell-imaging techniques. Here, we show that ROS are upregulated in chronic epilepsy and that ROS production contributes to cell death, which is seen after status epilepticus (SE) and chronic seizures. Inhibition of ROS production by AEBSF, a NADPH oxidase inhibitor, markedly reduced seizure-induced cell death in the perforant path model of epilepsy. These findings demonstrate a critical role for ROS, generated by NADPH oxidase, contributing to seizure-induced cell death. These findings point to NADPH oxidase inhibition as a novel treatment strategy to prevent brain injury in SE and chronic epilepsy.

Divergent roles for ferric ions in the biological activity of amidated and non-amidated gastrins.

Amidated forms of the peptide hormone gastrin act via the cholecystokinin-2 receptor to stimulate gastric acid secretion, whereas non-amidated forms stimulate colonic mucosal proliferation via a novel, as yet uncharacterised, receptor. Nuclear magnetic resonance (NMR) and fluorescence spectroscopic studies have revealed that glycine-extended gastrin17 bound two ferric ions, and that ferric ion binding was essential for biological activity. We have therefore investigated the role of ferric ions in the biological activity of amidated gastrin17. As with glycine-extended gastrin17, fluorescence quenching experiments indicated that Glu7 Ala and Glu8,9 Ala mutants of amidated gastrin17 each bound only one ferric ion. The affinity of the mutant peptides for the cholecystokinin-2 receptor on transfected COS-7 cells or on Tlymphoblastoid Jurkat cells, and their potency in stimulation of proliferation in Jurkat cells and inositol phosphate production in transfected COS-7 cells, were similar to the values obtained for amidated gastrin17. In addition, the iron chelator desferrioxamine did not significantly inhibit either binding of amidated gastrin17 to the cholecystokinin-2 receptor, or stimulation of inositol phosphate production by amidated gastrin17 in transfected COS-7 cells. We conclude that, in contrast to glycine-extended gastrin17, binding of ferric ions is not essential for the biological activity of amidated gastrin17. Our results support the concept of distinct modes of action for amidated and non-amidated gastrins, and raise the possibility of developing selective antagonists of the actions of non-amidated and amidated gastrins.

Intramyometrial coring as an adjunct to vaginal hysterectomy.

A retrospective review of 902 hysterectomies, 727 (80.6%) performed vaginally and 175 (19.4%) abdominally, is presented. The technique of intramyometrial coring was used in 76% of the vaginal hysterectomy group. Surgical indications, length of surgery, length of hospital stay, and complications are analyzed. The evidence presented suggests that intramyometrial coring may be used for the vaginal removal of many uteri for which abdominal hysterectomy has been traditionally the procedure of choice. The clinical findings confirm that vaginal hysterectomies with intramyometrial coring are associated with lower morbidity and a significant decrease in length of hospitalization.

Transvaginal hysterectomy: rationale and surgical approach.

Abdominal hysterectomy is performed in the United States at a 3:1 ratio over vaginal hysterectomy, despite evidence that vaginal hysterectomy offers advantages over abdominal hysterectomy with regard to operative time, complication rates, recovery, return to daily activities, and overall costs of treatment. In fact, the predominance of the abdominal approach may be based on factors other than clinical considerations, including resident training, use of limited or obsolete guidelines, greater third-party compensation for abdominal procedures, a presumption rather than a confirmation that pathology exists that contraindicates a vaginal approach, and misconceptions about the safety and cost of vaginal hysterectomy. A number of studies spanning several years demonstrate that the use of more systematic guidelines for selecting the route of hysterectomy results in a major shift toward the vaginal approach. Evidence also shows that transvaginal hysterectomy is both feasible and optimum for types of patients who have long been considered inappropriate candidates for the vaginal route. New instrumentation facilitates the vaginal approach and contributes to improved hemostasis and decreased operative time. Included here is a step-by-step approach to determining appropriate candidates for the vaginal approach via assessment of access, uterus size, and extent of pathology.

Hysterectomy outcomes in patients with similar indications.

OBJECTIVE: To investigate the cost advantages and complication rates associated with surgical routes of uncomplicated hysterectomies in which uteri weigh less than 280 g and benign diseases are confined to the uterus. METHODS: Data were collected prospectively from 1988 to 1993 from 4609 consecutive women who had hysterectomies at a single institution. Women who had abdominal hysterectomies, laparoscopically assisted vaginal hysterectomies, or vaginal hysterectomies were selected if they had benign diseases confined to the uterus (adenomyosis, leiomyomas, abnormal uterine bleeding, cervical carcinoma in situ, and prolapse) and uterine weights less than 280 g. We compared length of stay, hospital charges, and associated complications between groups. RESULTS: A total of 1427 women met the study criteria. Length of stay was longer after abdominal hysterectomies than laparoscopically assisted vaginal hysterectomies or vaginal hysterectomies (3.99 +/- 1.16 days, 2.45 +/- 1.58 days, and 2.76 +/- 0.94 days, respectively; P <.001). Hospital charges for vaginal hysterectomies were significantly lower than for either abdominal or laparoscopically assisted vaginal hysterectomies (P <.001). The median charge for vaginal hysterectomies was $4166; the median charges for laparoscopically assisted vaginal hysterectomies and abdominal hysterectomies were 71% and 35% higher than this, respectively. There was a higher risk of one or more complications after abdominal hysterectomies (9.3%) than after laparoscopically assisted vaginal hysterectomies (3.6%; P <.001) or vaginal hysterectomies (5.3%; P <.001). The incidence of postoperative infection or fever was higher after abdominal than after vaginal hysterectomies (4.0% versus 0.8%; P =.029). CONCLUSION: This study supports the vaginal route of hysterectomy when disease is confined to the uterus and uterine weight is less than 280 g.

Guidelines to determine the route of hysterectomy.

OBJECTIVE: To 1) test the validity of a method of assigning patients prospectively to a vaginal, abdominal, or laparoscopy-assisted vaginal approach to hysterectomy for benign disease; 2) compare the outcomes of these options from the day of surgery to the first day of returning to normal activities; and 3) estimate the proportion of hysterectomies by each route when patients were assigned according to this system, and the impact on hospital charges. METHODS: Six hundred seventeen women were assigned to a route of hysterectomy on the basis of uterine size (greater or less than 280 g), presumptive risk factors, and uterine or adnexal immobility or inaccessibility. Data regarding the success of the procedure, complications, length of hospital stay and convalescence, and hospital charges were compiled. RESULTS: Vaginal hysterectomy alone (n = 548) or in conjunction with laparoscopy (n = 63) was successful in 99.5% of women assigned to these groups. Patients in whom the vaginal route was successful included 94% of those with uterine weights exceeding 280 g and 97% of those having risk factors often cited as reasons for selecting abdominal hysterectomy. Laparoscopic surgery was necessary to permit a transvaginal operation in only 12 of 63 patients (19%). Use of the guidelines produced a potential savings of 615 hospital days, $1,317,434 in hospital charges, and 7250 convalescent days relative to the 3:1 ratio of abdominal to vaginal hysterectomies prevalent in the United States. CONCLUSIONS: Specific guidelines for uterine size, risk factors, and uterine and adnexal mobility and accessibility are useful in selecting the operative approach to hysterectomy and will significantly reduce the number of abdominal operations performed. Laparoscopy is valuable in properly selected patients to determine the route of hysterectomy, but the need for laparoscopic techniques to permit a vaginal operation may be considerably less than some investigators have proposed.

Pubic bone suburethral stabilization sling for recurrent urinary incontinence.

A suburethral sling anchored to the posterior-inferior aspect of the pubic bone with bone screws placed transvaginally is described for recurrent urinary incontinence. The technique involves placing a suburethral patch of a synthetic fiber at the junction of the upper one-third and lower two-thirds of the urethra and securing it by titanium bone screws to the posterior-inferior pubis for site-specific urethral support and stabilization of normally positioned continence anatomy. The procedure was performed from August 1990 through December 1991 in 27 patients with recurrent stress urinary incontinence after previous urinary incontinence surgery, of whom 25 patients were followed yearly until August 1994. None of these 25 patients have had a recurrence as of August 1996. The initial success of the pubic bone suburethral stabilization sling merits further study for the cure of urinary incontinence in patients with a hypermobile urethra or low-pressure urethral conditions.