Clear‐cell ependymoma: A report of intracortical tumor with significant desmoplasia

We report a case of clear‐cell ependymoma in a 20‐month‐old girl who presented with seizures. The tumor had several uncommon features including a solid consistency, a purely intracortical location, and a remarkable degree of desmoplasia. Clinical, radiological, and pathological findings are presented. This case emphasizes the value of ultrastructural studies in pathological work‐up of brain tumors.     

Close association of HLA-B51 in persons with recurrent aphthous stomatitis.

The HLA typing profile of 26 Israeli subjects with recurrent aphthous stomatitis (RAS) was examined and compared with that of 100 healthy control subjects. HLA-B51 was found in six subjects (23%) with RAS and in nine control subjects (9%) (p < 0.05). HLA-Cw7 was found in six subjects with RAS (23%) and in five control subjects (5%) (p < 0.01). Eleven subjects had first-degree relatives who had RAS. Because a high frequency of HLA-B51 has been found in Behcet's syndrome and aphthous stomatitis is part of this syndrome, it is suggested that in some subjects with RAS the entire syndrome may actually develop in the future.     

Cervical paraspinal electromyography: normal values in 100 control subjects.

The normal electromyographic values and the significance of spontaneous activity, when examining the cervical paraspinal muscles, has been studied rarely, and there are very few studies concerning this issue.To obtain muscle unit potential (MUP) reference values for cervical paraspinal muscles, we examined 100 volunteers. Spontaneous activity and the analysis of 20 MUPs in every individual were checked by the automated MUP analysis program.In those individuals ages 20 to 40 years, no spontaneous activity was observed, and in the ones ages 40 to 60 years and 60 years or older, fibrillations and/or positive sharp waves were seen in 8% and 92%, respectively. MUP values were found to be close to those of upper limb muscles. Age has no significant effect on MUP values, except for mean amplitude that was increased in individuals ages 60 to 80 years.Our findings suggest that fibrillations and positive sharp waves do not have much electrodiagnostic value in the study of cervical paraspinal muscles of middle-aged and elderly subjects, when it is an isolated finding, and there is a need for an extended electromyographic examination, including other muscles, to exclude radiculopathy. Automated MUP analysis is easily performed, and our results may serve as reference values.     

Effect of extracorporeal piezoelectric lithotripsy shock waves on renal function measured by Tc-99m-DMSA using spect

Extracorporeal shock-wave lithotripsy has altered the therapeutic approach to urinary stone disease. Recently, a method was developed in which shock-wave generation is obtained piezoelectrically. To evaluate the effect of extracorporeal piezoelectric lithotripsy (EPL) on renal function, 20 patients were studied prior to and after EPL of renal calculi. Renal cortical function was evaluated by using a previously described and validated quantitative single photon emission computerized tomography (SPECT) method to measure individual absolute uptake of technetium-99m dimercaptosuccinic acid (Tc-99m-DMSA). Twenty kidneys were treated, and the 19 contralateral kidneys were without stone disease (1 patient had a single kidney). The absolute kidney uptake of Tc-DMSA in the normal kidneys was 21.4% +/- 6.2% before and 22.2% +/- 6.4% after EPL. For the treated kidneys the absolute update was 16.8% +/- 5.3% and 16.8% +/- 4.7% before and after, respectively. There was no statistical significant difference between pre- and post-treatment values. The absolute kidney uptake was significantly lower (p less than 0.01) in the treated than in the normal kidneys. This study indicates that the EPL procedure did not cause any damage to cortical function detectable by the DMSA uptake.     

GABAB receptor deficiency causes failure of neuronal homeostasis in hippocampal networks

Stabilization of neuronal activity by homeostatic control systems is fundamental for proper functioning of neural circuits. Failure in neuronal homeostasis has been hypothesized to underlie common pathophysiological mechanisms in a variety of brain disorders. However, the key molecules regulating homeostasis in central mammalian neural circuits remain obscure. Here, we show that selective inactivation of GABA_B, but not GABA_A, receptors impairs firing rate homeostasis by disrupting synaptic homeostatic plasticity in hippocampal networks. Pharmacological GABA_B receptor (GABA_BR) blockade or genetic deletion of the GB_1a receptor subunit disrupts homeostatic regulation of synaptic vesicle release. GABA_BRs mediate adaptive presynaptic enhancement to neuronal inactivity by two principle mechanisms: First, neuronal silencing promotes syntaxin-1 switch from a closed to an open conformation to accelerate soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly, and second, it boosts spike-evoked presynaptic calcium flux. In both cases, neuronal inactivity removes tonic block imposed by the presynaptic, GB_1a-containing receptors on syntaxin-1 opening and calcium entry to enhance probability of vesicle fusion. We identified the GB_1a intracellular domain essential for the presynaptic homeostatic response by tuning intermolecular interactions among the receptor, syntaxin-1, and the Ca_V2.2 channel. The presynaptic adaptations were accompanied by scaling of excitatory quantal amplitude via the postsynaptic, GB_1b-containing receptors. Thus, GABA_BRs sense chronic perturbations in GABA levels and transduce it to homeostatic changes in synaptic strength. Our results reveal a novel role for GABA_BR as a key regulator of population firing stability and propose that disruption of homeostatic synaptic plasticity may underlie seizure''s persistence in the absence of functional GABA_BRs.Neural circuits achieve an ongoing balance between plasticity and stability to enable adaptations to constantly changing environments while maintaining neuronal activity within a stable regime. Hebbian-like plasticity, reflected by persistent changes in synaptic and intrinsic properties, is crucial for refinement of neural circuits and information storage; however, alone it is unlikely to account for the stable functioning of neural networks (1). In the last 2 decades, major progress has been made toward understanding the homeostatic negative feedback systems underlying restoration of a baseline neuronal function after prolonged activity perturbations (2–4). Homeostatic processes may counteract the instability by adjusting intrinsic neuronal excitability, inhibition-to-excitation balance, and synaptic strength via postsynaptic or presynaptic modifications (5, 6) through a profound molecular reorganization of synaptic proteins (7, 8). These stabilizing mechanisms have been collectively termed homeostatic plasticity. Homeostatic mechanisms enable invariant firing rates and patterns of neural networks composed from intrinsically unstable activity patterns of individual neurons (9).However, nervous systems are not always capable of maintaining constant output. Although some mutations, genetic knockouts, or pharmacologic perturbations induce a compensatory response that restores network firing properties around a predefined “set point” (10), the others remain uncompensated, or their compensation leads to pathological function (11). The inability of neural networks to compensate for a perturbation may result in epilepsy and various types of psychiatric disorders (12). Therefore, determining under which conditions activity-dependent regulation fails to compensate for a perturbation and identifying the key regulatory molecules of neuronal homeostasis is critical for understanding the function and malfunction of central neural circuits.In this work, we explored the mechanisms underlying the failure in stabilizing hippocampal network activity by combining long-term extracellular spike recordings by multielectrode arrays (MEAs), intracellular patch-clamp recordings of synaptic responses, imaging of synaptic vesicle exocytosis, and calcium dynamics, together with FRET-based analysis of intermolecular interactions at individual synapses. Our results demonstrate that metabotropic, G protein-coupled receptors for GABA, GABA_BRs, are essential for firing rate homeostasis in hippocampal networks. We explored the mechanisms by which GABA_BRs gate homeostatic synaptic plasticity. Our study raises the possibility that persistence of epileptic seizures in GABA_BR-deficient mice (13–15) is directly linked to impairments in a homeostatic control system.