, a bio/informatics shared resource is still "open for business" - Visit the CDS website


Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 93

Publication Record

Connections

In Reply: Seizure Outcomes in Occipital Lobe and Posterior Quadrant Epilepsy Surgery: A Systematic Review and Meta-Analysis.
Harward SC, Englot DJ
(2019) Neurosurgery 84: E449
MeSH Terms: Epilepsy, Humans, Occipital Lobe, Seizures
Added June 22, 2019
0 Communities
1 Members
0 Resources
4 MeSH Terms
Vagus Nerve Stimulation for the Treatment of Epilepsy.
González HFJ, Yengo-Kahn A, Englot DJ
(2019) Neurosurg Clin N Am 30: 219-230
MeSH Terms: Epilepsy, Humans, Seizures, Treatment Outcome, Vagus Nerve Stimulation
Show Abstract · Added June 22, 2019
Vagus nerve stimulation (VNS) was the first neuromodulation device approved for treatment of epilepsy. In more than 20 years of study, VNS has consistently demonstrated efficacy in treating epilepsy. After 2 years, approximately 50% of patients experience at least 50% reduced seizure frequency. Adverse events with VNS treatment are rare and include surgical adverse events (including infection, vocal cord paresis, and so forth) and stimulation side effects (hoarseness, voice change, and cough). Future developments in VNS, including closed-loop and noninvasive stimulation, may reduce side effects or increase efficacy of VNS.
Copyright © 2018 Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
MeSH Terms
A Novel M PAM VU0486846 Exerts Efficacy in Cognition Models without Displaying Agonist Activity or Cholinergic Toxicity.
Rook JM, Bertron JL, Cho HP, Garcia-Barrantes PM, Moran SP, Maksymetz JT, Nance KD, Dickerson JW, Remke DH, Chang S, Harp JM, Blobaum AL, Niswender CM, Jones CK, Stauffer SR, Conn PJ, Lindsley CW
(2018) ACS Chem Neurosci 9: 2274-2285
MeSH Terms: Allosteric Regulation, Animals, Antipsychotic Agents, CHO Cells, Cognition, Cognitive Dysfunction, Conditioning, Psychological, Cricetulus, Exploratory Behavior, Fear, Mice, Morpholines, Prefrontal Cortex, Pyrazoles, Rats, Risperidone, Seizures
Show Abstract · Added March 3, 2020
Selective activation of the M subtype of muscarinic acetylcholine receptor, via positive allosteric modulation (PAM), is an exciting strategy to improve cognition in schizophrenia and Alzheimer's disease patients. However, highly potent M ago-PAMs, such as MK-7622, PF-06764427, and PF-06827443, can engender excessive activation of M, leading to agonist actions in the prefrontal cortex (PFC) that impair cognitive function, induce behavioral convulsions, and result in other classic cholinergic adverse events (AEs). Here, we report a fundamentally new and highly selective M PAM, VU0486846. VU0486846 possesses only weak agonist activity in M-expressing cell lines with high receptor reserve and is devoid of agonist actions in the PFC, unlike previously reported ago-PAMs MK-7622, PF-06764427, and PF-06827443. Moreover, VU0486846 shows no interaction with antagonist binding at the orthosteric acetylcholine (ACh) site (e.g., neither bitopic nor displaying negative cooperativity with [H]-NMS binding at the orthosteric site), no seizure liability at high brain exposures, and no cholinergic AEs. However, as opposed to ago-PAMs, VU0486846 produces robust efficacy in the novel object recognition model of cognitive function. Importantly, we show for the first time that an M PAM can reverse the cognitive deficits induced by atypical antipsychotics, such as risperidone. These findings further strengthen the argument that compounds with modest in vitro M PAM activity (EC > 100 nM) and pure-PAM activity in native tissues display robust procognitive efficacy without AEs mediated by excessive activation of M. Overall, the combination of compound assessment with recombinant in vitro assays (mindful of receptor reserve), native tissue systems (PFC), and phenotypic screens (behavioral convulsions) is essential to fully understand and evaluate lead compounds and enhance success in clinical development.
0 Communities
1 Members
0 Resources
MeSH Terms
PF-06827443 Displays Robust Allosteric Agonist and Positive Allosteric Modulator Activity in High Receptor Reserve and Native Systems.
Moran SP, Cho HP, Maksymetz J, Remke DH, Hanson RM, Niswender CM, Lindsley CW, Rook JM, Conn PJ
(2018) ACS Chem Neurosci 9: 2218-2224
MeSH Terms: Allosteric Regulation, Animals, CHO Cells, Calcium, Cricetulus, Dogs, Humans, Isoindoles, Mice, Oxazoles, Patch-Clamp Techniques, Prefrontal Cortex, Rats, Receptor, Muscarinic M1, Seizures
Show Abstract · Added March 3, 2020
Positive allosteric modulators (PAMs) of the M subtype of muscarinic acetylcholine receptor have attracted intense interest as an exciting new approach for improving the cognitive deficits in schizophrenia and Alzheimer's disease. Recent evidence suggests that the presence of intrinsic agonist activity of some M PAMs may reduce efficacy and contribute to adverse effect liability. However, the M PAM PF-06827443 was reported to have only weak agonist activity at human M receptors but produced M-dependent adverse effects. We now report that PF-06827443 is an allosteric agonist in cell lines expressing rat, dog, and human M and use of inducible cell lines shows that agonist activity of PF-06827443 is dependent on receptor reserve. Furthermore, PF-06827443 is an agonist in native tissue preparations and induces behavioral convulsions in mice similar to other ago-PAMs. These findings suggest that PF-06827443 is a robust ago-PAM, independent of species, in cell lines and native systems.
0 Communities
2 Members
0 Resources
MeSH Terms
Children with sickle cell anemia with normal transcranial Doppler ultrasounds and without silent infarcts have a low incidence of new strokes.
Jordan LC, Roberts Williams DO, Rodeghier MJ, Covert Greene BV, Ponisio MR, Casella JF, McKinstry RC, Noetzel MJ, Kirkham FJ, Meier ER, Fuh B, McNaull M, Sarnaik S, Majumdar S, McCavit TL, DeBaun MR
(2018) Am J Hematol 93: 760-768
MeSH Terms: Adolescent, Anemia, Sickle Cell, Cerebral Infarction, Child, Child, Preschool, Humans, Incidence, Ischemic Attack, Transient, Prospective Studies, Seizures, Stroke, Ultrasonography, Doppler, Transcranial
Show Abstract · Added March 24, 2020
In a prospective cohort study, we tested the hypothesis that children with sickle cell anemia (SCA) with normal transcranial Doppler ultrasound (TCD) velocities and without silent cerebral infarcts (SCIs) would have a lower incidence rate of new neurological events (strokes, seizures or transient ischemic attacks) compared to children with normal TCD measurements and SCIs, not receiving regular blood transfusions. Nonrandomized participants from the silent cerebral infarct transfusion (SIT) Trial who had screening magnetic resonance imaging (MRI) of the brain and normal TCD measurements were included. Follow-up ended at the time of first neurological event (stroke, seizure or transient ischemic attack), start of regular blood transfusion, or loss to follow-up, whichever came first. The primary endpoint was a new neurological event. Of 421 participants included, 68 had suspected SCIs. Mean follow-up was 3.6 years. Incidence rates of new neurological events in nontransfused participants with normal TCD values with SCIs and without SCIs were 1.71 and 0.47 neurological events per 100 patient-years, respectively, P = .065. The absence of SCI(s) at baseline was associated with a decreased risk of a new neurological event (hazard ratio 0.231, 95% CI 0.062-0.858; P = .029). Local pediatric neurologists examined 67 of 68 participants with suspected SCIs and identified 2 with overt strokes classified as SCIs by local hematologists; subsequently one had a seizure and the other an ischemic stroke. Children with SCA, without SCIs, and normal TCD measurements have a significantly lower rate of new neurological events when compared to those with SCIs and normal TCD measurements. Pediatric neurology assessment may assist risk stratification.
© 2018 Wiley Periodicals, Inc.
0 Communities
1 Members
0 Resources
MeSH Terms
Acute Management of Traumatic Brain Injury.
Vella MA, Crandall ML, Patel MB
(2017) Surg Clin North Am 97: 1015-1030
MeSH Terms: Brain Injuries, Traumatic, Humans, Intracranial Hypertension, Intracranial Pressure, Seizures
Show Abstract · Added June 26, 2018
Traumatic brain injury (TBI) is a leading cause of death and disability in patients with trauma. Management strategies must focus on preventing secondary injury by avoiding hypotension and hypoxia and maintaining appropriate cerebral perfusion pressure (CPP), which is a surrogate for cerebral blood flow. CPP can be maintained by increasing mean arterial pressure, decreasing intracranial pressure, or both. The goal should be euvolemia and avoidance of hypotension. Other factors that deserve important consideration in the acute management of patients with TBI are venous thromboembolism, stress ulcer, and seizure prophylaxis, as well as nutritional and metabolic optimization.
Published by Elsevier Inc.
0 Communities
1 Members
0 Resources
MeSH Terms
Unexpected Efficacy of a Novel Sodium Channel Modulator in Dravet Syndrome.
Anderson LL, Hawkins NA, Thompson CH, Kearney JA, George AL
(2017) Sci Rep 7: 1682
MeSH Terms: Action Potentials, Animals, Epilepsies, Myoclonic, Ion Channel Gating, Mice, Inbred C57BL, Mice, Knockout, NAV1.1 Voltage-Gated Sodium Channel, NAV1.6 Voltage-Gated Sodium Channel, Neurons, Pyramidal Cells, Pyridines, Seizures, Survival Analysis, Triazoles
Show Abstract · Added October 2, 2018
Dravet syndrome, an epileptic encephalopathy affecting children, largely results from heterozygous loss-of-function mutations in the brain voltage-gated sodium channel gene SCN1A. Heterozygous Scn1a knockout (Scn1a ) mice recapitulate the severe epilepsy phenotype of Dravet syndrome and are an accepted animal model. Because clinical observations suggest conventional sodium channel blocking antiepileptic drugs may worsen the disease, we predicted the phenotype of Scn1a mice would be exacerbated by GS967, a potent, unconventional sodium channel blocker. Unexpectedly, GS967 significantly improved survival of Scn1a mice and suppressed spontaneous seizures. By contrast, lamotrigine exacerbated the seizure phenotype. Electrophysiological recordings of acutely dissociated neurons revealed that chronic GS967-treatment had no impact on evoked action potential firing frequency of interneurons, but did suppress aberrant spontaneous firing of pyramidal neurons and was associated with significantly lower sodium current density. Lamotrigine had no effects on neuronal excitability of either neuron subtype. Additionally, chronically GS967-treated Scn1a mice exhibited normalized pyramidal neuron sodium current density and reduced hippocampal Na1.6 protein levels, whereas lamotrigine treatment had no effect on either pyramidal neuron sodium current or hippocampal Na1.6 levels. Our findings demonstrate unexpected efficacy of a novel sodium channel blocker in Dravet syndrome and suggest a potential mechanism involving a secondary change in Na1.6.
1 Communities
0 Members
0 Resources
14 MeSH Terms
Chloride Dysregulation, Seizures, and Cerebral Edema: A Relationship with Therapeutic Potential.
Glykys J, Dzhala V, Egawa K, Kahle KT, Delpire E, Staley K
(2017) Trends Neurosci 40: 276-294
MeSH Terms: Animals, Brain Edema, Brain Injuries, Traumatic, Chlorides, Extracellular Matrix, Humans, Neurons, Seizures, Symporters
Show Abstract · Added May 3, 2017
Pharmacoresistant seizures and cytotoxic cerebral edema are serious complications of ischemic and traumatic brain injury. Intraneuronal Cl concentration ([Cl]) regulation impacts on both cell volume homeostasis and Cl-permeable GABA receptor-dependent membrane excitability. Understanding the pleiotropic molecular determinants of neuronal [Cl] - cytoplasmic impermeant anions, polyanionic extracellular matrix (ECM) glycoproteins, and plasmalemmal Cl transporters - could help the identification of novel anticonvulsive and neuroprotective targets. The cation/Cl cotransporters and ECM metalloproteinases may be particularly druggable targets for intervention. We establish here a paradigm that accounts for recent data regarding the complex regulatory mechanisms of neuronal [Cl] and how these mechanisms impact on neuronal volume and excitability. We propose approaches to modulate [Cl] that are relevant for two common clinical sequela of brain injury: edema and seizures.
Copyright © 2017 Elsevier Ltd. All rights reserved.
0 Communities
1 Members
0 Resources
9 MeSH Terms
Seizure Outcomes in Occipital Lobe and Posterior Quadrant Epilepsy Surgery: A Systematic Review and Meta-Analysis.
Harward SC, Chen WC, Rolston JD, Haglund MM, Englot DJ
(2018) Neurosurgery 82: 350-358
MeSH Terms: Drug Resistant Epilepsy, Electroencephalography, Epilepsies, Partial, Female, Humans, Male, Seizures, Treatment Outcome, Vision Disorders
Show Abstract · Added June 23, 2017
BACKGROUND - Occipital lobe epilepsy (OLE) is an uncommon but debilitating focal epilepsy syndrome with seizures often refractory to medical management. While surgical resection has proven a viable treatment, previous studies examining postoperative seizure freedom rates are limited by small sample size and patient heterogeneity, thus exhibiting significant variability in their results.
OBJECTIVE - To review the medical literature on OLE so as to investigate rates and predictors of both seizure freedom and visual outcomes following surgery.
METHODS - We reviewed manuscripts exploring surgical resection for drug-resistant OLE published between January 1990 and June 2015 on PubMed. Seizure freedom rates were analyzed and potential predictors were evaluated with separate meta-analyses. Postoperative visual outcomes were also examined.
RESULTS - We identified 27 case series comprising 584 patients with greater than 1 yr of follow-up. Postoperative seizure freedom (Engel class I outcome) was observed in 65% of patients, and was significantly predicted by age less than 18 yr (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.13-2.18), focal lesion on pathological analysis (OR 2.08, 95% CI 1.58-2.89), and abnormal preoperative magnetic resonance imaging (OR 3.24, 95% 2.03-6.55). Of these patients, 175 also had visual outcomes reported with 57% demonstrating some degree of visual decline following surgery. We did not find any relationship between postoperative visual and seizure outcomes.
CONCLUSION - Surgical resection for OLE is associated with favorable outcomes with nearly two-thirds of patients achieving postoperative seizure freedom. However, patients must be counseled regarding the risk of visual decline following surgery.
Copyright © 2017 by the Congress of Neurological Surgeons
0 Communities
1 Members
0 Resources
9 MeSH Terms
Mutant IDH1 and seizures in patients with glioma.
Chen H, Judkins J, Thomas C, Wu M, Khoury L, Benjamin CG, Pacione D, Golfinos JG, Kumthekar P, Ghamsari F, Chen L, Lein P, Chetkovich DM, Snuderl M, Horbinski C
(2017) Neurology 88: 1805-1813
MeSH Terms: Action Potentials, Animals, Brain Neoplasms, Cells, Cultured, Cerebral Cortex, Chromosome Deletion, Chromosomes, Human, Pair 1, Female, Glioma, Glutarates, Humans, Isocitrate Dehydrogenase, Male, Middle Aged, Mutation, Neoplasm Grading, Neurons, Rats, Sprague-Dawley, Retrospective Studies, Seizures
Show Abstract · Added April 2, 2019
OBJECTIVE - Because the d-2-hydroxyglutarate (D2HG) product of mutant isocitrate dehydrogenase 1 (IDH1) is released by tumor cells into the microenvironment and is structurally similar to the excitatory neurotransmitter glutamate, we sought to determine whether IDH1 increases the risk of seizures in patients with glioma, and whether D2HG increases the electrical activity of neurons.
METHODS - Three WHO grade II-IV glioma cohorts from separate institutions (total N = 712) were retrospectively assessed for the presence of preoperative seizures and tumor location, WHO grade, 1p/19q codeletion, and IDH1 status. Rat cortical neurons were grown on microelectrode arrays, and their electrical activity was measured before and after treatment with exogenous D2HG, in the presence or absence of the selective NMDA antagonist, AP5.
RESULTS - Preoperative seizures were observed in 18%-34% of IDH1 wild-type (IDH1) patients and in 59%-74% of IDH1 patients ( < 0.001). Multivariable analysis, including WHO grade, 1p/19q codeletion, and temporal lobe location, showed that IDH1 was an independent correlate with seizures (odds ratio 2.5, 95% confidence interval 1.6-3.9, < 0.001). Exogenous D2HG increased the firing rate of cultured rat cortical neurons 4- to 6-fold, but was completely blocked by AP5.
CONCLUSIONS - The D2HG product of IDH1 may increase neuronal activity by mimicking the activity of glutamate on the NMDA receptor, and IDH1 gliomas are more likely to cause seizures in patients. This has rapid translational implications for the personalized management of tumor-associated epilepsy, as targeted IDH1 inhibitors may improve antiepileptic therapy in patients with IDH1 gliomas.
© 2017 American Academy of Neurology.
0 Communities
1 Members
0 Resources
MeSH Terms