Altered neuronal and microglial responses to excitotoxic and ischemic brain injury in mice lacking TNF receptors.

Brain injury, as occurs in stroke or head trauma, induces a dramatic increase in levels of tumor necrosis factor-alpha (TNF), but its role in brain injury response is unknown. We generated mice genetically deficient in TNF receptors (TNFR-KO) to determine the role of TNF in brain cell injury responses. Damage to neurons caused by focal cerebral ischemia and epileptic seizures was exacerbated in TNFR-KO mice, indicating that TNF serves a neuroprotective function. Oxidative stress was increased and levels of an antioxidant enzyme reduced in brain cells of TNFR-KO mice, indicating that TNF protects neurons by stimulating antioxidant pathways. Injury-induced microglial activation was suppressed in TNFR-KO mice, demonstrating a key role for TNF in injury-induced immune response. Drugs that target TNF signaling pathways may prove beneficial in treating stroke and traumatic brain injury.

Surgical treatment of independent bitemporal lobe epilepsy defined by invasive recordings.

OBJECTIVES: Bitemporal lobe epilepsy is commonly encountered in the evaluation of pharmacoresistant epilepsy. Yet the role of surgery in the management of these patients is unclear. This study evaluates the impact of surgery on seizure tendency and quality of life, as well as prognostic indicators in individuals with proven ictal onset bitemporal lobe epilepsy. METHODS: The study population comprised all patients who underwent temporal lobe surgery over a 10 year period and had ictal onset bitemporal lobe epilepsy identified with intracranial electrode monitoring. Patients with extratemporal seizure generators were excluded. Subjects were divided into a favourable or less favourable group based on the results of surgery on seizure tendency. RESULTS: 11 subjects were studied with a mean 5.9 years of post-surgical follow-up. Six subjects constituted the favourable outcome group. Four had a less favourable outcome and continued to have frequent seizures after surgery; however, three with less favourable seizure reduction subjectively reported improvement in quality of life after surgery as a result of reduced seizure frequency and severity, and reduced medications. No single preoperative factor was significantly different between the groups, including ictal EEG laterality, epilepsy duration, age at surgery, age at seizure onset and mesial temporal atrophy. CONCLUSIONS: Surgical resection is an important treatment option for medically intractable bitemporal epilepsy. The proportion of seizures arising from one temporal lobe is not reliable as a single indicator to prognosticate the results of surgery on seizure tendency. In addition, individuals who achieved only palliation by reducing seizure frequency experienced improvement in quality of life.

Localizing value of alpha-methyl-L-tryptophan PET in intractable epilepsy of neocortical origin.

BACKGROUND: [(11)C] alpha-methyl-L-tryptophan (alpha-MTrp) has been developed as a tracer for the study of the synthesis of serotonin in the brain with PET. However, it has been shown that in pathologic conditions the tracer may reflect the activation of kynurenine metabolism. Increased levels of serotonin and quinolinic acid have been described in resected epileptogenic cortex, raising the possibility that alpha-MTrp can localize seizure foci in patients with intractable partial epilepsy. The authors assessed the uptake of alpha-MTrp in 18 patients (11 men, mean +/- SD age 27.1 +/- 10.1 years, range 13 to 54) with intractable partial epilepsy to correlate the PET findings with the epileptogenic area defined by electroclinical and neuroimaging data. METHOD: Seven patients with cortical dysplasia (CD) and 11 with partial epilepsy in which conventional MRI and fluorine-18-deoxyglucose ((18)FDG)-PET studies failed to detect any abnormality were studied. All underwent scalp EEG monitoring during the PET scan to exclude ictal events and estimate the interictal epileptic activity. RESULTS: In seven patients (39%; CD four and cryptogenic partial epilepsy three), PET showed focal increased uptake of alpha-MTrp corresponding to the epileptogenic area. alpha-MTrp uptake in the epileptic focus correlated with the frequency of interictal spikes (r = 0.7, p < 0.05). CONCLUSIONS: alpha-MTrp-PET may be of value in the localization of the epileptogenic area not only in patients with visible dysplastic lesions, but also in those with cryptogenic partial epilepsy.

A review of stress ulcer prophylaxis in the neurosurgical intensive care unit.

STRESS ULCERS OCCUR frequently in intensive care unit patients who have intracranial disease. After major physiological stress, endoscopic evidence of mucosal lesions of the gastrointestinal tract appears within 24 hours of injury; 17% of these erosions progress to clinically significant bleeding. Gastrointestinal hemorrhage has been associated with mortality rates of up to 50%. The pathogenesis of stress ulcers may not be completely understood, but gastric acid and pepsin appear to play significant roles. Antacids, H2 antagonists, and sucralfate are effective prophylactic agents in the medical/surgical intensive care unit. Appropriate therapy for neurosurgical patients remains unclear, however. This review summarizes the current literature regarding the pathogenesis and therapy of stress ulcers in neurosurgical patients.

Relationships between the epileptic focus and hand area in central epilepsy: combining dipole models and anatomical landmarks.

OBJECT: When considering resection of epileptic generators near the central sulcus, it is essential to define the spatial relationship between the epileptic generator and the primary sensorimotor hand area. In this study, the authors assessed the accuracy of dipole modeling of electroencephalographic spikes and median nerve somatosensory evoked potentials (SSEPs) in defining this relationship preoperatively and noninvasively. METHODS: Epileptic spikes and SSEPs in patients with focal central area epilepsy were represented by dipole models coregistered onto global magnetic resonance images. In patients who underwent surgery, spike dipoles were also compared with findings of electrocorticography (ECoG) and with the resection area. To improve the accuracy of the dipole models, anatomical landmarks of the hand area were used to assess the error in SSEP dipole location, and this error measure was used to correct the location of spike dipoles. Five patients with central epilepsy were studied, three of whom underwent ECoG-guided surgical resections. The location of SSEP dipoles correlated well with anatomical landmarks of the primary sensory hand area. The relative position of the spike and SSEP dipoles correlated well with the patients' ictal symptoms, ECoG findings, and the location of the epileptic focus (as defined by the resection cavity in patients who became seizure free postoperatively). Corrected spike dipoles were located even closer to the resection cavity. CONCLUSIONS: The calculation of the relative location of spike and SSEP dipoles is a simple noninvasive method of determining the relationship between the primary hand area and an epileptic focus in the central area. The spatial resolution of this technique can be further improved using easily identifiable anatomical landmarks.

Localization of hand motor activation in Broca's pli de passage moyen.

OBJECT: The object of this study was to identify a reliable surface landmark for the hand motor area and to demonstrate that it corresponds to a specific structural component of the precentral gyrus. METHODS: Positron emission tomography (PET) activation studies for hand motor function were reviewed in 12 patients in whom magnetic resonance imaging results were normal. Each patient performed a hand opening and closing task. Using a computer-assisted three-dimensional reconstruction of the surface of each hemisphere studied, the relationship of the hand motor area with cortical surface landmarks was evaluated. CONCLUSIONS: The region of hand motor activation can be reliably identified on the surface of the brain by assessing anatomical relationships to nearby structures. After identification of the central sulcus, the superior and middle frontal gyrus can be seen to arise from the precentral gyrus at a perpendicular angle. A bend or genu in the precentral gyrus is constantly seen between the superior and middle frontal gyrus, which points posteriorly (posteriorly convex). The location of hand motor function, identified using PET activation studies, is within the central sulcus at the apex of this posteriorly pointing genu. The apex of the genu of the precentral gyrus leads to a deep cortical fold connecting the pre- and postcentral gyri and elevating the floor of the central sulcus. This deep fold was described by Paul Broca as the pli de passage fronto-parietal moyen, and the precentral bank of the pli de passage represents the anatomical substratum of hand motor function. Observers blinded to the results of the activation studies were able to identify the hand motor area reliably after instruction in using these surface landmarks.

Surgery for temporal lobe epilepsy in older patients.

OBJECT: The goal of this study was to evaluate the efficacy of surgery for temporal lobe epilepsy (TLE) in older (> or = 50 years of age) patients. METHODS: The authors conducted a review of all patients 50 years of age or older with TLE surgically treated at the Montreal Neurological Institute and Hospital since 1981 by one surgeon (A.O.). Only patients without a mass lesion were included. Outcome parameters were compared with those of younger individuals with TLE, who were stratified by age at operation. In patients aged 50 years and older, the onset of complex partial seizures occurred 5 to 53 years (mean 35 years) prior to the time of surgery. Postoperatively, over a mean follow-up period of 64 months, 15 patients (83%) obtained a meaningful improvement, becoming either free from seizures or only experiencing a rare seizure. Most surgery outcomes were similar in both older and younger individuals, except for a trend to more freedom from seizures and increased likelihood of returning to work or usual activities in the younger patients. Note that a patient's long-standing seizure disorder did not negatively affect their ability to achieve freedom from seizures following surgery. CONCLUSIONS: Surgery for TLE appears to be effective for older individuals, comparing favorably with results in younger age groups, and carries a small risk of postoperative complications.

The French contribution to the discovery of the central area.

French scientists in the 18th century and 19th century helped shape our modern conception of the anatomy and physiology of the nervous system. One of the fruits of this labor was the discovery of the central area. In 1786, Vicq d'Azyr published a treatise which illustrated the central area for the first time. Forty years later Rolando, in Turin, also illustrated the central area and recognized Vicq d'Azyr's priority. However, Leuret named the central sulcus for Rolando. Gall recognized the physiological importance of the cortex and its fixed gyral pattern, but the wild claims of phrenology prevented most of the scientific community from accepting his real contribution. Thirty-three years after Gall's death, Broca described his famous patient Leborgne with aphémie (aphasia) which spurred an explosion of research in cortical function and cerebral localization. Eminent French scientists like Gratiolet and Leuret were instrumental in demonstrating the fixed pattern of the convolutions and systematizing the study of the cortex in man and lower animals.

The current state of epilepsy surgery.

Epilepsy surgery is an effective therapy for many patients with refractory partial seizures. The results of epilepsy surgery have improved with advances in the evaluation of patients for surgery and the care of patients during and after surgery. This review looks at recent innovations in imaging modalities to identify the candidates for surgery who will benefit most, to identify subtle pathology, to resect the epileptogenic focus more precisely, and to preserve functionally important cortex in order to achieve the best possible outcome. Patient selection and the identification and removal of the epileptogenic focus, in a safe manner, are crucial for good outcome.

Health-related quality of life in gynecological oncology: instruments and psychometric properties.

Quality of life is generally recognized as a subjective, multidimensional concept, which places emphasis on the self-perception and subjective experience of the patient compared to the expectation of an individual's current health state. Health-related quality of life, which encompasses the psychological, physical, and social functioning of patients, has evolved over recent decades into an established treatment outcome in cancer clinical trials. Assessing quality of life as a clinical trial outcome enables clinicians to better address concerns of gynecological oncology patients, but selection of appropriate measurement tools is critical. This article reviews the concepts of reliability and validity, and describes three health-related quality of life instruments, their psychometric properties, and their use in gynecological oncology clinical trials and other cancer research.