Neurovascular coupling is optimized to compensate for the increase in proton production from nonoxidative glycolysis and glycogenolysis during brain activation and maintain homeostasis of pH, pCO, and pO.

During transient brain activation cerebral blood flow (CBF) increases substantially more than cerebral metabolic rate of oxygen consumption (CMRO) resulting in blood hyperoxygenation, the basis of BOLD-fMRI contrast. Explanations for the high CBF versus CMRO slope, termed neurovascular coupling (NVC) constant, focused on maintenance of tissue oxygenation to support mitochondrial ATP production. However, paradoxically the brain has a 3-fold lower oxygen extraction fraction (OEF) than other organs with high energy requirements, like heart and muscle during exercise.

Elevated homocarnosine and GABA in subject on isoniazid as assessed through 1H MRS at 7T.

Typical magnetic resonance spectroscopy J-editing methods designed to quantify GABA suffer from contamination of both overlapping macromolecules and homocarnosine signal, introducing potential confounds. The aim of this study was to develop a novel method to assess accurately both the relative concentrations of homocarnosine as well as GABA free from overlapping creatine, homocarnosine and macromolecule signal. A novel method which utilized the combination of echo time STEAM and MEGA-sLASER magnetic resonance spectroscopy experiments at 7T were used to quantify the concentration of GABA and homocarnsoine independently, which are typically quantified in tandem.

Deep Versus Lobar Intraparenchymal Hemorrhage: Seizures, Hyperexcitable Patterns, and Clinical Outcomes.

Objectives: To compare electrographic seizures, hyperexcitable patterns, and clinical outcomes in lobar and deep intraparenchymal hemorrhage. Additionally, to characterize electrographic seizure and hyperexcitable pattern predictors in each group and determine seizure risk with thalamic involvement.

Design: Retrospective cohort study.

The use and yield of continuous EEG in critically ill patients: A comparative study of three centers.

Objective: Continuous EEG (cEEG) monitoring of critically ill patients has gained widespread use, but there is substantial reported variability in its use. We analyzed cEEG and antiseizure drug (ASD) usage at three high volume centers.

Methods: We utilized a multicenter cEEG database used daily as a clinical reporting tool in three tertiary care sites (Emory Hospital, Brigham and Women's Hospital and Yale - New Haven Hospital).

Cyclic seizures in critically ill patients: Clinical correlates, DC recordings and outcomes.

Objective: To describe EEG and clinical correlates, DC recordings and prognostic significance of cyclic seizures (CS).

Methods: We reviewed our prospective continuous EEG database to identify patients with CS, controls with non-cyclic status epilepticus (SE) and controls without seizure matched for age and etiology. EEG was reviewed with DC settings.

A comparison of the power spectral density of scalp EEG and subjacent electrocorticograms.

Objective: Our study investigated the effects of the intact skull on background EEG rhythms recorded simultaneously by subdural electrocorticography (ECoG) and scalp EEG.

Methods: We performed a retrospective analysis of twenty patients undergoing intracranial EEG monitoring. EEG and ECoG were recorded simultaneously from the central and occipital scalp and subjacent subdural electrodes removed (median 46 mm, interquartile 27-65) from the craniotomy.

Clinical Correlates and Prognostic Significance of Lateralized Periodic Discharges in Patients Without Acute or Progressive Brain Injury: A Case-Control Study.

Purpose: Lateralized periodic discharges (LPDs, also known as periodic lateralized epileptiform discharges) in conjunction with acute brain injuries are known to be associated with worse prognosis but little is known about their importance in absence of such acute injuries. We studied the clinical correlates and outcome of patients with LPDs in the absence of acute or progressive brain injury.

Methods: This is a case-control study of 74 patients with no acute brain injury undergoing continuous EEG monitoring, half with LPDs and half without, matched for age and etiology of remote brain injury, if any, or history of epilepsy.

Brief potentially ictal rhythmic discharges in critically ill adults.

Importance: Brief potentially ictal rhythmic discharges, termed B(I)RDs, have been described mainly in neonates, and their significance in adults remains unclear.

Objective: To describe the incidence of B(I)RDs in critically ill patients and investigate their association with seizures and outcome.

Design, Setting, And Participants: We reviewed the records of prospectively identified patients with B(I)RDs and patients serving as controls matched for age (±5 years) and primary diagnosis.

Similarity of lateralized rhythmic delta activity to periodic lateralized epileptiform discharges in critically ill patients.

Importance: The increasing use of continuous electroencephalography (EEG) monitoring in the intensive care unit has led to recognition of new EEG patterns that are of unclear or unknown significance.

Objective: To describe an EEG pattern, lateralized rhythmic delta activity (LRDA), encountered in critically ill subjects and determine its clinical significance in this setting. DESIGN, SETTING, AND PARTICIPANTS Retrospective review at an academic medical center of EEG recordings, medical records, and imaging studies of critically ill patients with LRDA and comparison with subjects with lateralized periodic discharges (also known as periodic lateralized epileptiform discharges), subjects with focal nonrhythmic slowing, and controls.

Blockade of GABA synthesis only affects neural excitability under activated conditions in rat hippocampal slices.

The primary goal of this study was to establish whether inhibition of GABA synthesis was sufficient to induce network hyperexcitability in a rat hippocampal slice model comparable to that seen with GABA receptor blockade. We used field and intracellular recordings from the CA1 region of rat hippocampal slices to determine the physiological effects of blocking GABA synthesis with the convulsant, 3-mercaptoproprionic acid (MPA). We measured the rate of synthesis of GABA and glutamate in slices using 2-13C-glucose as a label source and liquid chromatography-tandem mass spectrometry.

Neurometabolism in human epilepsy.

Purpose: Because of the large and continuous energetic requirements of brain function, neurometabolic dysfunction is a key pathophysiologic aspect of the epileptic brain. Additionally, neurometabolic dysfunction has many self-propagating features that are typical of epileptogenic processes, that is, where each occurrence makes the likelihood of further mitochondrial and energetic injury more probable. Thus abnormal neurometabolism may be not only a chronic accompaniment of the epileptic brain, but also a direct contributor to epileptogenesis.

Glutamate and astrocytes--key players in human mesial temporal lobe epilepsy?

Approximately one-third of all patients with epilepsy continue to suffer from seizures even after appropriate treatment with antiepileptic drugs. Medically refractory epilepsies are associated with considerable morbidity and mortality, and more efficacious therapies against these disorders are clearly needed. However, the discovery of better therapies has been lagging due to an incomplete understanding of the mechanisms underlying the development of epilepsy (epileptogensis) and seizures (ictogenesis) in humans.

Brain homocarnosine and seizure control of patients taking gabapentin or topiramate.

Purpose: To assess the relation between seizure control and brain homocarnosine and gamma-aminobutyric acid (GABA) levels of patients with complex partial seizures taking gabapentin (GBP) or topiramate (TPM) as adjunctive therapy.

Methods: In vivo measurements of GABA and homocarnosine were made of a 14-cc volume in the occipital cortex by using (1)H spectroscopy with a 2.1-Tesla magnetic resonance spectrometer and an 8-cm surface coil.

Acute effects of gabapentin and pregabalin on rat forebrain cellular GABA, glutamate, and glutamine concentrations.

The effects of antiepileptic drugs, gabapentin, pregabalin and vigabatrin, on brain gamma-aminobutyric acid (GABA), glutamate and glutamine concentrations were studied in Long Evans rats using proton magnetic resonance spectroscopy (MRS) of perchloric acid extracts. Cellular glutamate concentrations significantly decreased by 7% (P<0.05) 2 hours after intraperitoneal injection of 100mg/kg gabapentin and 4% (P<0.

N-acetyl-aspartate, total creatine, and myo-inositol in the epileptogenic human hippocampus.

Background: Mesial temporal lobe epilepsy (mTLE) is characterized by hippocampal atrophy, decreased N-acetyl-aspartate, and a low N-acetyl-aspartate/total creatine ratio, often attributed to neuron loss and gliosis. Qualitative studies reported that N-acetyl-aspartate content was significantly lower in hippocampal sclerosis.

Objective: It was proposed to measure the effects of neuron loss and gliosis on the hippocampal content of N-acetyl-aspartate, total creatine, and myo-inositol in mTLE.

GABA and glutamate in the human brain.

Cortical excitability reflects a balance between excitation and inhibition. Glutamate is the main excitatory and GABA the main inhibitory neurotransmitter in the mammalian cortex. Changes in glutamate and GABA metabolism may play important roles in the control of cortical excitability.

Neuronal and glial metabolite content of the epileptogenic human hippocampus.

Mesial temporal lobe epilepsy is characterized by hippocampal atrophy, hypometabolism, and decreased N-acetylaspartate, often attributed to neuron loss and gliosis. Twenty hippocampal specimens were obtained during temporal lobectomy and frozen quickly. Perchloric acid extracts of the small metabolites were analyzed by proton magnetic resonance spectroscopy.

Glutamate-glutamine cycling in the epileptic human hippocampus.

Purpose: Several findings suggest that energy metabolism and the glutamate-glutamine cycle may be impaired in epilepsy. Positron emission tomography often shows interictal hypometabolism of the epileptogenic hippocampus. In vivo microdialysis studies show that seizure-associated glutamate release is doubled, and clearance is slowed.

Gabapentin and vigabatrin increase GABA in the human neocortical slice.

The effects of antiepileptic drugs, gabapentin and vigabatrin, on gamma-aminobutyric acid (GABA) concentrations were studied in human (n=14) and rat (n=6) neocortical slice preparations. In this study, neocortical slices were incubated with gabapentin, vigabatrin or no drugs for 3 h in an oxygenated environment. Proton magnetic resonance spectroscopy (MRS) of perchloric acid (PCA) extracts was used to measure GABA concentrations.