Intergenerational effects of racism on amygdala and hippocampus resting state functional connectivity.

Racism is an insidious problem with far-reaching effects on the lives of Black, Indigenous, and People of Color (BIPOC). The pervasive negative impact of racism on mental health is well documented. However, less is known about the potential downstream impacts of maternal experiences of racism on offspring neurodevelopment. This study sought to examine evidence for a biological pathway of intergenerational transmission of racism-related trauma. This study examined the effects of self-reported maternal experiences of racism on resting state functional connectivity (rsFC) in n = 25 neonates (13 female, 12 male) birthed by BIPOC mothers. Amygdala and hippocampus are brain regions involved in fear, memory, and anxiety, and are central nodes in brain networks associated with trauma-related change. We used average scores on the Experiences of Racism Scale as a continuous, voxel-wise regressor in seed-based, whole-brain connectivity analysis of anatomically defined amygdala and hippocampus seed regions of interest. All analyses controlled for infant sex and gestational age at the 2-week scanning session. More maternal racism-related experiences were associated with (1) stronger right amygdala rsFC with visual cortex and thalamus; and (2) stronger hippocampus rsFC with visual cortex and a temporo-parietal network, in neonates. The results of this research have implications for understanding how maternal experiences of racism may alter neurodevelopment, and for related social policy.

Low Pressure Tolerance by Methanogens in an Aqueous Environment: Implications for Subsurface Life on Mars.

The low pressure at the surface of Mars (average: 6 mbar) is one potentially biocidal factor that any extant life on the planet would need to endure. Near subsurface life, while shielded from ultraviolet radiation, would also be exposed to this low pressure environment, as the atmospheric gas-phase pressure increases very gradually with depth. Few studies have focused on low pressure as inhibitory to the growth or survival of organisms. However, recent work has uncovered a potential constraint to bacterial growth below 25 mbar. The study reported here tested the survivability of four methanogen species (Methanothermobacter wolfeii, Methanosarcina barkeri, Methanobacterium formicicum, Methanococcus maripaludis) under low pressure conditions approaching average martian surface pressure (6 mbar - 143 mbar) in an aqueous environment. Each of the four species survived exposure of varying length (3 days - 21 days) at pressures down to 6 mbar. This research is an important stepping-stone to determining if methanogens can actively metabolize/grow under these low pressures. Additionally, the recently discovered recurring slope lineae suggest that liquid water columns may connect the surface to deeper levels in the subsurface. If that is the case, any organism being transported in the water column would encounter the changing pressures during the transport.

A comprehensive study in triblock copolymer membrane interaction.

Poloxamers are triblock copolymers made of poly(ethylene glycol)-(poly(propylene glycol))-poly(ethylene glycol). They have been shown to enhance gene transfer in the muscle, and co-administration of polymers and DNA appeared to be crucial to obtain this effect. It is questionable then if some interaction occurs between polymers and DNA. Polymer interaction with membranes represents a second crucial point due to the central hydrophobic part of the triblock copolymers. Besides, the question of the polymer spanning or adsorbing to the surface has not been solved by now. We addressed these issues by means of sensitive techniques that allowed working in diluted conditions and gaining in comprehension of gene transfection. By means of simultaneous time-correlated single-photon counting and fluorescence correlation spectroscopy, we have shown that the diffusion time of a single DNA molecule and PicoGreen lifetime was not altered in the presence of the triblock copolymer L64. Polypropylene (glycol) interactions with dodecylphosphocholine micelles were shown to occur at a deep level by (1)H NMR using doxyl probes located at the head or the lipid extremity of the micelles. The polypropylene (glycol) also interacted with lipid bilayers in a manner dependent on the cholesterol content, as shown by differential scanning calorimetry using liposomes. This interaction destabilised the membrane and allowed the release of small molecules. Finally, molecular dynamic simulation of the copolymer L64 in the presence of dodecylphosphocholine showed that the hydrophobic core of the polymer formed an extremely tight cluster, whose dimensions excluded the possibility of polymer spanning across the lipidic micelles. The simulation positively correlated with the destabilising effect observed on the liposomal membrane models.

Dietary energy density increases during early childhood irrespective of familial predisposition to obesity: results from a prospective cohort study.

OBJECTIVE: This study compared 4-year changes in daily energy density (ED; kcal/g) in children born at different risk for obesity, characterized the stability of ED and examined associations between ED and child body composition. DESIGN: Prospective cohort study to measure habitual dietary ED of children who are born at different risk for obesity. SUBJECTS: Children who were born at high risk (n=22) or low risk (n=27) for obesity based on maternal pre-pregnancy weight. MEASUREMENTS: Three-day food records were collected from children's mothers at child ages 3, 4, 5 and 6 years. Three categories of ED were computed (food only, food and milk, and food and all beverages) and body composition assessed at each year. RESULTS: The mean (+/-s.e.m.) ED increased over time across all children (linear trend: P<0.003): 2.18+/-0.07 to 2.32+/-0.06 kcal/g (food only); 1.66+/-0.07 to 1.82+/-0.06 kcal/g (food and milk); and 1.24+/-0.04 to 1.37+/-0.05 kcal/g (food and all beverages). Intraindividual coefficients of variation were smaller than those previously reported for adults. Weight indices were not correlated with dietary ED (P>0.05). CONCLUSION: Dietary ED increased in young children, irrespective of their predisposition to obesity, between the ages of 3 and 6 years. The genes that promote childhood obesity may not exert their influence through dietary ED, which may be more strongly influenced by environmental factors.

Focal cortical dysplasia: long term seizure outcome after surgical treatment.

BACKGROUND: Studies of long term outcome after epilepsy surgery for cortical malformations are rare. In this study, we report our experience with surgical treatment and year to year long term outcome for a subgroup of patients with focal cortical dysplasia (FCD). METHODS: We retrospectively analysed the records of 49 patients (females n = 26; males n = 23; mean age 25 (11) years) with a mean duration of epilepsy of 18 years (range 1-45). Preoperative MRI, histological results based on the Palmini classification and clinical year to year follow-up according to the International League Against Epilepsy (ILAE) classification were available in all patients. RESULTS: 98% of patients had a lesion on preoperative MRI. In addition to lobectomy (n = 9) or lesionectomy (n = 40), 14 patients had multiple subpial transections of the eloquent cortex. The resected tissue was classified as FCD type II b in 41 cases with an extratemporal (88%) and FCD type II a in 8 cases with a temporal localisation (100%). After a mean follow-up of 8.1 (4.5) years, 37 patients (76%) were seizure free, a subgroup of 23 patients (47%) had been completely seizure free since surgery (ILAE class 1a) and 4 patients (8%) had only auras (ILAE class 2). Over a 10 year follow-up, the proportion of satisfactory outcomes decreased, mainly within the first 3 years. During long term follow-up, 48% stopped antiepileptic drug treatment, 34% received a driver's license and 57% found a job or training. CONCLUSION: Surgical treatment of epilepsy with FCD is not only successful in the short term but also has a satisfying long term outcome which remains constant after 3 years of follow-up but is not associated with better employment status or improvement in daily living.

Present practice and perspective of evaluation and surgery for temporal lobe epilepsy.

Surgery for temporal lobe epilepsy refractory to medical treatment is a promising treatment option. After a short overview of historical developments in this field, we describe the present practice of presurgical evaluation and resection strategies as practiced at our institution and review the corresponding publications from other centers. We will be trying to outline major future developments for the surgical therapy of temporal lobe epilepsy based on present trends.

Correlation of health-related quality of life after surgery for mesial temporal lobe epilepsy with two seizure outcome scales.

PURPOSE: The objective of this study was to correlate health-related quality of life (HRQOL) after surgery for mesial temporal lobe epilepsy, as revealed by a postoperative screening tool, to different modalities of seizure outcome classification (Engel, International League Against Epilepsy (ILAE)). METHOD: One hundred twenty-eight of one hundred forty consecutive patients returned a HRQOL questionnaire at a mean of 36 months after selective amygdalohippocampectomy. Patients answered in two ways: with an absolute estimation (values 1-4) and with a self-rated relative change (-1, 0, +1) after surgery. RESULTS: Eighty patients were seizure- and aura-free (63.3% ILAE 1), 16 continued to have auras (12.5% ILAE 2), and 13 experienced 1-3 seizure days per year after surgery (10.2% ILAE 3). Ninety-two patients were classified seizure-free (71.9% Engel I), and 17 had two or fewer seizures per year (13.3% Engel II). Of 110 patients in ILAE 1-3, 100 (91%) stated good or even very good postoperative HRQOL, and 99 (90.0%) reported improvements in HRQOL. Only 9 of the remaining 18 (50%) reported good or very good HRQOL after surgery (P=0.01). Corresponding results were obtained with Engel classes I and II, suggesting a trend toward ILAE 1-3 and Engel I and II as overall satisfactory outcomes. A more detailed HRQOL assessment yielded lowest scores in the cognitive domain, and a significant correlation of self-rated changes in cognitive functioning with seizure control (P=0.01). Changes in physical capabilities and mood were significantly better with satisfactory seizure outcome (P=0.006 and P<0.001, respectively), whereas the social aspects were not significantly dependent on seizure outcome (P=0.06). CONCLUSION: Correlation of HRQOL and seizure control suggested that ILAE 1-3 and Engel I and II most likely represent overall satisfactory outcome. Subdomain analyses revealed cognitive abilities as the most critical feature associated with seizure control, whereas social aspects remained mainly stable.

Calbindin-D28k content and firing pattern of hippocampal granule cells in amygdala-kindled rats: a perforated patch-clamp study.

The dentate gyrus is believed to play an important pathophysiological role during experimentally induced kindling. In this study, we investigated whether an altered content of the calcium binding protein calbindin-D(28k) or an increased intrinsic excitability of hippocampal granule cells contribute to the induction of the kindling phenomenon. We determined the firing pattern of granule cells in hippocampal slices using perforated patch-clamp recordings in current clamp mode. The expression of calbindin-D(28k) and glutamic acid decarboxylase (GAD(67)) by granule cells was analyzed immunohistochemically. Rats developed secondarily generalized limbic seizures within approximately 11 days of twice-daily stimulation of the amygdala. As reported for other kindling paradigms, this protocol induced a clear up-regulation of GAD(67) in granule cells, indicating their involvement in the induced neuronal activity. However, when comparing kindled and control rats, we could not detect any differences in intrinsic excitability: Firing frequency, after-hyperpolarisations, action potentials, input resistance and membrane potentials were nearly identical between both groups. Furthermore, we did not observe any differences in the calbindin-D(28k) immunoreactivity between groups. In every slice, virtually all granule cells were found to be strongly calbindin-D(28k) positive, and there was no apparent reduction in the general level of calbindin-D(28k) expression. We conclude that changes in intrinsic membrane properties or in the calbindin-D(28k) content of granule cells are not necessary for the development of amygdala kindling.

Lesional mesial temporal lobe epilepsy and limited resections: prognostic factors and outcome.

OBJECTIVES: To evaluate the influence of clinical, investigational, surgical, and histopathological factors on postoperative seizure relief in patients with mesial temporal lobe epilepsy (MTLE) due to lesions other than ammonshornsclerosis (AHS). METHODS: Of 738 patients operated for TLE, 78 patients underwent limited resections for lesional MTLE (1990-2000). Seventy four patients with a follow up of more than one year were included. The preoperative clinical, neuropsychological, electroencephalogram, and neuroimaging characteristics were prospectively collected in a database. The histopathological material was re-examined. RESULTS: The mean follow up was 49 months. Fifty eight patients were classified as seizure free (78.4% Class I), and six as almost seizure free (8.1% Class II), grouped together as satisfactory seizure control (64 patients, 86.5%). Five patients (6.8%) were categorised in Classes III and IV, respectively. These were grouped as unsatisfactory seizure control (10 patients, 13.5%). Surgical procedures were: 32 amygdalohippocampectomies (AH), 17 partial anterior AH, 15 AH plus polar resection, seven AH plus basal resection, and three AH plus extended temporal lesionectomy. There was no mortality and 2.7% mild permanent morbidity. Seizure relief did neither differ significantly with these approaches, nor with different classes of pathological findings (43 developmental tumours, 12 glial tumours, 10 dysplasias, and nine others). Even operation of dysplasias resulted in 80% satisfactory seizure control. Seizure onset during childhood proved to be a negative predictor for seizure relief (p = 0.020). MRI revealed 73 suspected lesions (98.6%), one dysembryoplastic neuroepithelial tumour was missed, in four cases no structural abnormalities could be confirmed with histopathological exam. Additionally, multifactorial regression revealed the factors "seizure onset after 10 years of age", "presence of complex partial seizures", "absence of a neurological deficit", and a "correlating neuropsychological deficit" as predictive for satisfactory seizure control. CONCLUSIONS: "Preoperative tailoring" resulting in limit resections has proven to be safe and to provide a very good chance for satisfactory seizure relief in patients with lesional MTLE.

Characterization of hemorrhagic complications after surgery for temporal lobe epilepsy.

OBJECTIVES: To assess the significance of symptomatic hemorrhagic complications occurring after different temporal resections for temporal lobe epilepsy (TLE) and to compare this data to findings with postoperative hematomas after temporal surgery for mostly glial or metastatic tumors. PATIENTS AND METHODS: Patient charts were retrospectively reviewed for 442 patients who underwent surgery for refractory TLE between 1995 and 2000. Procedures were 247 transsylvian amygdalohippocampectomies (AH), 40 transcortical AH, 57 anterior temporal lobectomies (ATL), 23 lesionectomies plus AH, and 75 lesionectomies without AH. All patients with delayed awakening or new neurological deficits due to hemorrhages were included in the study. An identical procedure was performed to detect symptomatic hemorrhages after 208 procedures for temporal tumor resection during the same time period. RESULTS: Symptomatic postoperative hemorrhages were found in 17 patients (3.8 %) undergoing epilepsy surgery, while the incidence was 3.0 % in a group with space-occupying temporal tumors (six patients). Hemorrhages showed a characteristic distribution after epilepsy surgery: in eight patients they were located remote from the site of surgery in the upper cerebellar vermis and foliae. Five typical hemorrhages associated with dysphasia were found in the left frontal operculum, only three patients had hematomas in the resection cavity, and one was located epidurally. Two patients had more than one location of hemorrhage. Transsylvian AH and ATL had a similar risk for postoperative hemorrhage, whereas none was found after lateral lesionectomies or transcortical AH. Intraoperative manipulations were associated with opercular hemorrhages; the only predisposing factor for resection site hematomas was older age, whereas cerebellar hemorrhages were associated with cerebrospinal fluid (CSF) loss during AH and ATL. There was no mortality in the TLE group, and 0.75 % permanent mild deficits. Seizure outcome did not differ from the rest of the group (82.5 % satisfactory seizure control). In contrast, all intraaxial hematomas after tumor surgery (N = 4, incidence 1.9 %) were located in or adjacent to the resection cavity. Prognosis was much worse with parenchymal hemorrhages after tumor surgery: three of four patients died, one survived with a severe hemiparesis, only two patients with extraaxial hematomas (incidence 1 %) had a complete recovery. The 3 % incidence of symptomatic hemorrhages was only insignificantly lower compared to the TLE group, patients with tumor surgery were older than TLE patients (49 versus 33 years), and in five of six patients only incomplete tumor resection was achieved. CONCLUSION: Although associated with a low permanent morbidity, features of postoperative hemorrhages after TLE surgery are characteristically different to complications after surgery for other indications, which has to be kept in mind for patient counseling and obtaining informed consent.

Outcome of epilepsy surgery in focal cortical dysplasia.

OBJECTIVE: To describe the outcome of surgery in patients with drug resistant epilepsy and a histopathological diagnosis of focal cortical dysplasia. METHODS AND SUBJECTS: Analysis of histories and presurgical and follow up data was carried out in 53 patients with a histological diagnosis of focal cortical dysplasia. Their mean age was 24.0 years (range 5 to 46), and they included 14 children and adolescents. Mean age at seizure onset was 12.4 years (0.4 to 36) and mean seizure duration was 11.6 years (1 to 45). RESULTS: The presurgical detection rate of focal cortical dysplasia with magnetic resonance imaging (MRI) was 96%. There were 24 temporal and 29 extratemporal resections; additional multiple subpial transections were done in 12 cases to prevent spread of seizure discharges. There was a 6% rate of complications with permanent neurological deficit, but no deaths. All resected specimens were classified by neuropathological criteria as focal cortical dysplasia. Balloon cells were seen in most cases of extratemporal focal cortical dysplasia. After a mean follow up of 50 months, 38 patients (72%) were seizure-free, two (4%) had less than two seizures a year, nine (17%) had a reduction of seizure frequency of more than 75%, and four (8%) had no improvement. Seizure outcome was similar after temporal and extratemporal surgery. The patients in need of multilobar surgery had the poorest outcome. CONCLUSIONS: Circumscribed lesionectomy of focal dysplastic lesions provides seizure relief in patients with chronic drug resistant temporal and extratemporal epilepsy. There was a trend for the best seizure outcome to be in patients with early presurgical evaluation and early surgery, and in whom lesions were identified on the preoperative MRI studies.

Down-regulation of mGluR8 in pilocarpine epileptic rats.

Activation of presynaptic metabotropic glutamate receptors (mGluRs) leads to a powerful inhibition of glutamate release from many synaptic terminals throughout the CNS. mGluRs as autoreceptors are believed to provide a negative feedback system that prevents potentially toxic accumulation of glutamate in the extracellular space during synchronous synaptic activity such as epileptic seizures. In this study we analyzed the function of presynaptic mGluR8 on terminals of the lateral perforant pathway in the pilocarpine model of limbic epilepsy. Field excitatory postsynaptic potentials (fEPSPs) recorded in hippocampal slices of rats that developed spontaneous recurrent seizures after pilocarpine-induced status epilepticus (SRS group) showed a significantly reduced sensitivity to Group III mGluR agonists and severe mossy fiber sprouting. The Group III mGluR agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4, 10 microM) depressed fEPSPs in the SRS group only by 26 +/- 21% compared to 50 +/- 18% in untreated rats. Similarly, the mGluR8 preferring agonist (R,S)-4-phosphonophenylglycine (PPG, 5 microM) was significantly less effective in slices from SRS rats (43 +/- 4% vs. 83 +/- 5%). Concentration-response curves for L-AP4 revealed that the EC(50) values were not different between the control and SRS group (13 +/- 7 microM vs. 9 +/- 9 microM), while the maximal depressing effect was significantly reduced. The remaining depressing effect of L-AP4 in the SRS group could be blocked by the Group III specific antagonists (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG) and alpha-methyl-L-AP4 (MAP4). Rats that did not develop SRS following pilocarpine-induced status epilepticus were indistinguishable from control rats: fEPSPs were highly sensitive to L-AP4 and there was no mossy fiber sprouting. The results show that pilocarpine-induced status epilepticus can lead to a downregulation of mGluR8 and suggest that the condition of SRS is associated with a deteriorated autoregulation of glutamate release.

Preoperative evaluation for epilepsy surgery (Bonn Algorithm).

SUMMARY: Epilepsy surgery has been established as a successful treatment in patients with drug-resistant focal epilepsies. Different standardized surgical approaches were developed for resective or functional treatment. Successful surgical treatment, however, necessitates a careful presurgical evaluation. Although there are international standards for non invasive and invasive presurgical procedures most centers differ in their diagnostic strategy. This article gives a survey of the Bonn Epilepsy surgery program within which more than 1300 patients have been treated. After the method of patient selection different we describe tools of non invasive and invasive evaluation. This article serves only as a description of current practice in one center with a relatively large volume of cases. It presents just one opinion of a specific group within a wide spectrum of possible algorithms for presurgical evaluation that have briefly been outlined for 33 centers in Engels book [4].

New-onset psychogenic seizures after intracranial neurosurgery.

BACKGROUND: Patients with physical brain abnormalities have an increased risk of developing psychogenic nonepileptic seizures (PNES). Here we describe patients who developed PNES after intracranial neurosurgery for indications other than the control of refractory epileptic seizures and explore whether neurosurgical intervention is at risk factor for PNES. METHOD: We searched the database of 372 patients diagnosed with PNES at our department over the last 10 years and identified 17 patients (4.6%) in whom PNES first started after intracranial neurosurgery. Surgical procedures included the complete or partial resection of a meningioma, AV malformation, cavernoma, plexus papilloma, neurinoma, astrocytoma, oligodendroglioma, dysontogenetic cyst, the drainage of a brain abscess and removal of a subdural hematoma. PNES were documented by ictal video-EEG, ictal EEG, or ictal observation and examination in all cases. The diagnosis of additional epileptic seizures were confirmed by ictal EEG/video-EEG, or made on the basis of a clinical assessment by an experienced epileptologist. FINDINGS: Five patients had purely psychogenic postoperative seizure disorders, twelve had epileptic and psychogenic attacks. Median age at neurosurgery was 32 years (range 5-54), median latency between surgery and onset of PNES was 1 year (range 0-17 years). INTERPRETATION: PNES may develop after intracranial neurosurgery undertaken for other indications than the control of refractory epileptic seizures. Younger patients with a history of pre-operative psychiatric problems or epileptic seizures and surgical complications may be at higher risk. A diagnosis of PNES should be considered in patients who develop refractory seizures after neurosurgery.

Does nutrition information about the energy density of meals affect food intake in normal-weight women?

This study investigated whether the energy density of foods affected energy intake when subjects were informed about the energy density of their meals. Forty normal-weight women ate breakfast, lunch, and dinner in the laboratory on three separate days. The entrée at each meal was varied in energy density to be either 1.25, 1.50, or 1.75 kcal/g (5.23, 6.28, or 7.32 kJ/g), but was held similar in macronutrient composition and palatability. On each day, the entrées at all three meals had the same energy density. All entrées were consumed ad libitum. Subjects were assigned to one of two groups. Subjects in the information group received a nutrition label with each meal, which showed the energy density of the entrée. Subjects in the no-information group did not receive any nutrition information. The results revealed that subjects in both groups had the same pattern of food intake across the three levels of energy density. Energy density significantly affected energy intake; subjects in both groups combined consumed 22% less energy in the condition of low energy density than in the condition of high energy density (p < 0.0001). These findings show that energy density can have a significant influence on energy intake, even when individuals are informed about the energy density of their meals.

Intracranial manifestation of osteosarcoma.

Involvement of the central nervous system in osteosarcoma is uncommon. These neoplasms are most often located at the metaphyses of tubular bones and rarely in flat bones of vertebra, ribs, pelvis, facial bones, or skull. Tumors of the latter bones may obviously spread into the cerebrum. Osteosarcomas primarily metastasize hematogenously to the lungs. Bone, lymph node, or brain metastases are mostly seen following or concomitantly with pulmonary metastatic disease. However, there are single cases of primary osteosarcoma of the brain parenchyma without bone association or tumor manifestation at other locations. Three illustrative cases highlight the diversity of the clinical presentation of cerebral osteosarcoma: a 22-year-old man with multiple brain metastases following late pulmonary relapse of an osteosarcoma of the tibia, a 31-year-old woman with an osteosarcoma of the left anterior cranial fossa arising from the skull base, and a 78-year-old man presenting with primary osteogenic sarcoma of the left frontal cerebral hemisphere. According to the current literature, 10-15% of all osteosarcoma patients experiencing relapse may beat risk for central nervous system metastases. To the authors' best knowledge, there are 11 cases of primary intracerebral or meningeal osteogenic sarcoma, including this case report, without any skeletal attachment.

Improved hybrid clamp: resolution of tail currents following single action potentials.

Hybrid clamp protocols, in which a discontinuous single electrode voltage clamp (dSEVC) amplifier is switched from current to voltage clamp during the recording, are frequently used to investigate conductance changes after high frequency trains of action potentials. This technique is advantageous because it combines physiological stimulation of the cell with the possibility of analyzing the consecutive conductance changes quantitatively. In this study an improved hybrid clamp protocol, called dynamic hybrid clamp, is developed that enables the experimenter to study tail currents after single action potentials. The protocol employs real time action potential detection to assure precise timing of the mode switch and utilizes an external sample and hold amplifier to avoid voltage steps during the switch to voltage clamp. With the use of whole-cell patch clamp recordings and high switching frequencies (> or =25 kHz), dSEVC can easily be started with a minimal delay (<1.5 ms) after single action potentials and tail currents underlying afterhyperpolarisations (AHPs) and afterdepolarisations ensuing single spikes are clearly resolved. The dynamic hybrid clamp should also be useful for analysis of spontaneously occurring events such as intrinsic or population bursts.

Presynaptic group II metabotropic glutamate receptors reduce stimulated and spontaneous transmitter release in human dentate gyrus.

Metabotropic glutamate receptors (mGluRs) control excitatory neurotransmission as inhibitory autoreceptors at many synapses throughout the CNS. Since pharmacological activation of mGluRs potently depresses excitatory transmission, anticonvulsive effects were found in a number of experimental epilepsies. However, although native rodent mGluRs and heterologously expressed human mGluRs have so far been investigated in great detail, our knowledge about native human mGluRs in situ is limited. Here we used acute human hippocampal slices prepared from hippocampi surgically removed for the treatment of temporal lobe epilepsy in order to investigate the modulation of glutamatergic transmission by human mGluRs at the perforant path-granule cell synapse. The broad spectrum mGluR agonist (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) profoundly and reversibly reduced field EPSPs (fEPSPs) with an EC(50) of 30+/-7.4 microM. Paired-pulse depression of fEPSPs was converted into strong facilitation. The inhibition of fEPSPs by ACPD was mimicked by the specific group II mGluR agonist (2S, 2'R, 3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV), while the specific group I agonist (S)-3,5-dihydroxyphenylglycine (DHPG) was ineffective. The effect of ACPD was blocked by group II antagonist (2S,3S,4S)-2methyl-2-(carboxycyclopropyl)glycine (MCCG) but was not changed by coapplication of the specific group III antagonist (S)2 amino2methyl4phosphonobutanoic acid (MAP4). ACPD reduced pharmacologically isolated intracellular EPSPs in granule cells to the same extent as fEPSPs, whereas a specific group III agonist had no effect on EPSPs. Whole-cell recordings from morphologically identified granule cells revealed that DCG-IV significantly reduced the frequency of miniature EPSCs (mEPSCs) in granule cells while the mean amplitude of mEPSCs was not affected. We conclude that in human dentate gyrus mGluR2/3 can almost completely depress glutamate release by a presynaptic mechanism which acts downstream of presynaptic voltage gated calcium-entry and most likely involves a direct modulation of the release machinery.

Vertebral artery injury after cervical spine trauma: a prospective study.

OBJECTIVES: Vertebral artery (VA) -injury is rarely symptomatic and can therefore easily be overlooked. However, thromboembolic complications may result in permanent morbidity or mortality due to brainstem ischemia and infarction. In this prospective study a standardized protocol for the diagnosis and management of VA-injury following blunt cervical spine trauma with subluxation or fractures affecting the transverse foramen was evaluated. METHODS: During a 48 months period 31 (12 female, 19 male; mean age 44.2 years) of 119 patients with blunt cervical spine trauma were suspicious for VA-injury and subjected to a predefined radiological work-up. Selective digital subtraction angiography (DSA) was performed at admission in 31 patients. For comparison magnetic resonance angiography (MRA) was added within 2 days in 7 patients. RESULTS: The incidence of VA injury detected by DSA (n = 5) was 4% in all types of blunt cervical spinal injury, 16% in cases suspicious for VA injury, i.e. cases with mono- or bifacet dislocation and/or cases with fractures extending into the transverse foramen. Unilateral VA-stenosis was found in 4 and VA-occlusion in one patients. In one case a VA-stenosis by an intimal flap after transverse foramen fracture was detected by DSA but not by MRA. In 2 patients with VA injury headache occurred without signs of vertebro-basilar insufficiency. All 5 patients with VA-injury were treated with anticoagulation without complications or side effects. 14 of 31 patients which had DSA/MRA had unstable spine conditions and were treated surgically within 4 days after admission. CONCLUSION: The subgroup of patients with dislocation or fracture related stenosis of the transverse foramen should undergo early angiography for establishment of anticoagulation to prevent thromboembolic complications. It appears that the radiological diagnosis of VA-insufficiency is more sensitive than clinical findings, which rarely indicate VA-insufficiency. In this series one VA injury was overlooked with MRA.

Vagus nerve stimulation: clinical experience in a large patient series.

During the last decade, intermittent electrical stimulation of the left cervical vagus nerve was established as a new add-on treatment of drug-resistant seizures. Particularly in Europe, the acceptance of vagus nerve stimulation (VNS) was tentative in the beginning because of unknown mechanisms of action. We report the outcome in a sample of 95 adult patients with drug-resistant seizures who have received implants since 1998. The last available follow-up data are included. Unavoidable medication changes (e.g., intoxication) were accepted to examine VNS under usual clinical conditions. Median percentage of reduction in seizure frequency as compared to baseline was 30%. The seizure responder rate (> or =50% reduction) was 45%. Four patients experienced total release from seizures. Adverse effects were mild in general. Seizure outcome was positively correlated with VNS duration. No potential clinical factor (e.g., syndrome, cause, or lesion) could be identified as an indicator of favorable outcome. Patients with on stimulation-on periods of 30 seconds (standard cycle) had a better outcome than patients with stimulation-on periods of 7 seconds (rapid cycle). During an embedded, randomized, controlled trial, no evidence was found for a differential outcome of initial standard cycle versus initial rapid cycle stimulation conditions. Taking into account the good cost-benefit ratio as well as positive effects on well-being, VNS has to be considered an appropriate strategy for the add-on treatment of drug-resistant seizures, particularly in cases not suitable for epilepsy surgery.