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  1. Article ; Online: 2DG and glycolysis as therapeutic targets for status epilepticus.

    Sutula, Thomas P / Fountain, Nathan B

    Epilepsy & behavior : E&B

    2023  Volume 140, Page(s) 109108

    Abstract: 2-deoxy-D-glucose (2DG) is a glucose analog differing from glucose only by removal of an oxygen atom at the 2 position, which prevents the isomerization of glucose-6-phosphate to fructose-6-phosphate, and thereby reversibly inhibits glycolysis. PET ... ...

    Abstract 2-deoxy-D-glucose (2DG) is a glucose analog differing from glucose only by removal of an oxygen atom at the 2 position, which prevents the isomerization of glucose-6-phosphate to fructose-6-phosphate, and thereby reversibly inhibits glycolysis. PET studies of regional brain glucose utilization positron-emitting 18F-2DG demonstrate that brain regions generating seizures have diminished glucose utilization during interictal conditions, but rapidly transition to markedly increased glucose delivery and utilization during seizures, particularly in status epilepticus (SE). 2-deoxy-D-glucose has acute antiseizure actions in multiple in vivo and in vitro seizure models, including models of SE induced by the chemo convulsants pilocarpine and kainic acid, suggesting that focal enhanced delivery of 2DG to ictal brain circuits is a potential novel anticonvulsant intervention for the treatment of SE.
    MeSH term(s) Humans ; Deoxyglucose/therapeutic use ; Deoxyglucose/pharmacology ; Status Epilepticus/chemically induced ; Status Epilepticus/drug therapy ; Seizures/drug therapy ; Glucose ; Glycolysis ; Pilocarpine/toxicity
    Chemical Substances Deoxyglucose (9G2MP84A8W) ; Glucose (IY9XDZ35W2) ; Pilocarpine (01MI4Q9DI3)
    Language English
    Publishing date 2023-02-16
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2010587-3
    ISSN 1525-5069 ; 1525-5050
    ISSN (online) 1525-5069
    ISSN 1525-5050
    DOI 10.1016/j.yebeh.2023.109108
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  2. Book: Pharmacologic treatment of epilepsy

    Cole, Andrew J. / Fountain, Nathan B.

    (CNS spectrums ; 15,3, Suppl. 5 : Expert review supplement ; Case in point: Evidence-based insights for epilepsy management ; Pt. 3)

    2010  

    Author's details authors Andrew J. Cole ; Nathan B. Fountain
    Series title CNS spectrums ; 15,3, Suppl. 5 : Expert review supplement
    Case in point: Evidence-based insights for epilepsy management ; Pt. 3
    Case in point ; Evidence based insights for epilepsy management
    Case in point ; Evidence-based insights for epilepsy management
    Collection Case in point ; Evidence based insights for epilepsy management
    Case in point ; Evidence-based insights for epilepsy management
    Language English
    Size 8 S.
    Publisher MBL Communications
    Publishing place New York, NY
    Publishing country United States
    Document type Book
    HBZ-ID HT016422972
    Database Catalogue ZB MED Medicine, Health

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    Zs A 5171 -15,Suppl.5- not available for loan Zeitschriften-Lesesaal

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  3. Article ; Online: A critical review of fosphenytoin sodium injection for the treatment of status epilepticus in adults and children.

    Clay, Jordan L / Fountain, Nathan B

    Expert review of neurotherapeutics

    2021  Volume 22, Issue 1, Page(s) 1–13

    Abstract: Introduction: Status epilepticus (SE) is a neurological emergency that can occur in patients with or without epilepsy. Rapid treatment is paramount to mitigate risks of neuronal injury, morbidity/mortality, and healthcare-cost burdens associated with SE. ...

    Abstract Introduction: Status epilepticus (SE) is a neurological emergency that can occur in patients with or without epilepsy. Rapid treatment is paramount to mitigate risks of neuronal injury, morbidity/mortality, and healthcare-cost burdens associated with SE. Fosphenytoin is the prodrug of phenytoin designed to enable faster administration and improved tolerability as compared to intravenous (IV) phenytoin in the treatment of SE.
    Areas covered: This review evaluates the chemistry, pharmacokinetics, pharmacodynamics, safety, and tolerability of fosphenytoin. Efficacy data for fosphenytoin in the treatment of SE in adults and children are analyzed from initial phase I trials in 1988 through current phase III trials, including the Established Status Epilepticus Treatment Trial (ESETT).
    Expert opinion: IV phenytoin is an established treatment of SE, but its alkaline aqueous vehicle is associated with dermatologic irritation and systemic complications when rapidly infused. The water-soluble nature of its prodrug, fosphenytoin, allows for rapid infusion, and it is rapidly converted to phenytoin when administered intravenously or intramuscularly. In the ESETT, IV fosphenytoin demonstrated similar efficacy in treatment of established SE when compared to IV levetiracetam and IV valproate in adults and children, making it a reasonable choice in the treatment of SE that is unresponsive to benzodiazepines.
    MeSH term(s) Adult ; Anticonvulsants ; Child ; Humans ; Levetiracetam/adverse effects ; Phenytoin/adverse effects ; Phenytoin/analogs & derivatives ; Phenytoin/therapeutic use ; Status Epilepticus/drug therapy
    Chemical Substances Anticonvulsants ; Levetiracetam (44YRR34555) ; Phenytoin (6158TKW0C5) ; fosphenytoin (B4SF212641)
    Language English
    Publishing date 2021-12-19
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2112534-X
    ISSN 1744-8360 ; 1473-7175
    ISSN (online) 1744-8360
    ISSN 1473-7175
    DOI 10.1080/14737175.2021.2001328
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  4. Article ; Online: Analysis of seizure-cluster circadian periodicity from a long-term, open-label safety study of diazepam nasal spray.

    Fountain, Nathan B / Quigg, Mark / Murchison, Charles F / Carrazana, Enrique / Rabinowicz, Adrian L

    Epilepsia

    2024  Volume 65, Issue 4, Page(s) 920–928

    Abstract: Objective: Seizure clusters require prompt medical treatment to minimize possible progression to status epilepticus, increased health care use, and disruptions to daily life. Isolated seizures may exhibit cyclical patterns, including circadian and ... ...

    Abstract Objective: Seizure clusters require prompt medical treatment to minimize possible progression to status epilepticus, increased health care use, and disruptions to daily life. Isolated seizures may exhibit cyclical patterns, including circadian and longer rhythms. However, little is known about the cyclical patterns in seizure clusters. This post hoc analysis of data from a long-term, phase 3, open-label, repeat-dose safety study of diazepam nasal spray modeled the periodicity of treated seizure clusters.
    Methods: Mixed-effects cosinor analysis evaluated circadian rhythmicity, and single component cosinors using 12 and 24 h were used to calculate cosinor parameters (e.g., midline statistic of rhythm, wave ampitude, and acrophase [peak]). Analysis was completed for the full cohort and a consistent cohort of participants with two or more seizure clusters in each of four, 3-month periods. The influence of epilepsy type on cosinor parameters was also analyzed.
    Results: Seizure-cluster events plotted across 24 h showed a bimodal distribution with acrophases (peaks) at ~06:30 and ~18:30. A 12-h plot showed a single peak at ~06:30. Cosinor analyses of the full and consistent cohort aligned, with acrophases for both models predicting peak seizure activity at ~23:30 on a 24-h scale and ~07:30 on a 12-h scale. The consistent cohort was associated with increases in baseline and peak seizure-cluster activity. Analysis by epilepsy type identified distinct trends. Seizure clusters in the focal epilepsy group peaked in the evening (acrophase 19:19), whereas events in the generalized epilepsy group peaked in the morning (acrophase 04:46). Together they compose the bimodal clustering observed over 24 h.
    Significance: This analysis of seizure clusters treated with diazepam nasal spray demonstrated that seizure clusters occur cyclically in 12- and 24-h time frames similar to that reported with isolated seizures. Further elucidation of these patterns may provide important information for patient care, ranging from improved patient-centered outcomes to seizure-cluster prediction.
    MeSH term(s) Humans ; Anticonvulsants/adverse effects ; Circadian Rhythm ; Diazepam/adverse effects ; Epilepsy/drug therapy ; Epilepsy, Generalized/drug therapy ; Nasal Sprays ; Seizures/drug therapy
    Chemical Substances Anticonvulsants ; Diazepam (Q3JTX2Q7TU) ; Nasal Sprays
    Language English
    Publishing date 2024-02-23
    Publishing country United States
    Document type Clinical Trial, Phase III ; Journal Article
    ZDB-ID 216382-2
    ISSN 1528-1167 ; 0013-9580
    ISSN (online) 1528-1167
    ISSN 0013-9580
    DOI 10.1111/epi.17911
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  5. Article: Obliterating the Seizure Focus in AVMs is Effective: More Clinical Data Confirming Common Sense.

    Fountain, Nathan B

    Epilepsy currents

    2013  Volume 13, Issue 1, Page(s) 9–10

    Language English
    Publishing date 2013-02-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2270080-8
    ISSN 1535-7597
    ISSN 1535-7597
    DOI 10.5698/1535-7511-13.1.9
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  6. Article ; Online: Delivering quality care in epilepsy.

    Fountain, Nathan B

    Current opinion in neurology

    2013  Volume 26, Issue 2, Page(s) 174–178

    Abstract: Purpose of review: The science of quality of care in medicine has been emerging for the past decade, but it has only recently addressed epilepsy care. Quality of care in this sense refers to implementation of policies in large populations to improve ... ...

    Abstract Purpose of review: The science of quality of care in medicine has been emerging for the past decade, but it has only recently addressed epilepsy care. Quality of care in this sense refers to implementation of policies in large populations to improve care. This can have a large impact on epilepsy patients, as much of their care is delivered by generalists who can improve their care through the explicit direct requirements of quality measures.
    Recent findings: Eight epilepsy quality performance measures were recently approved by national organizations, but only three were adopted by Medicare and only one by the National Quality Forum. The main reason for not adopting them is the lack of high-level evidence. However, there is high-level evidence for the efficacy of epilepsy surgery and use of newer antiepileptic drugs for the treatment of intractable epilepsy. Other problems are the lack of information about gaps in care and the imprecision in epilepsy diagnosis coding.
    Summary: Quality measurement will continue in epilepsy care, so a working knowledge of the topic is required by healthcare providers. Implementation of standardized quality measures can improve the care of people with epilepsy if the measures have demonstrated efficacy and can address gaps in care, and implementation is feasible.
    MeSH term(s) Delivery of Health Care/standards ; Epilepsy/therapy ; Humans ; Medicare/standards ; United States
    Language English
    Publishing date 2013-04
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1182686-1
    ISSN 1473-6551 ; 1350-7540
    ISSN (online) 1473-6551
    ISSN 1350-7540
    DOI 10.1097/WCO.0b013e32835ee563
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  7. Article ; Online: Time-to-event clinical trial designs: Existing evidence and remaining concerns.

    Kerr, Wesley T / Auvin, Stéphane / Van der Geyten, Serge / Kenney, Christopher / Novak, Gerald / Fountain, Nathan B / Grzeskowiak, Caitlin / French, Jacqueline A

    Epilepsia

    2023  Volume 64, Issue 7, Page(s) 1699–1708

    Abstract: Well-designed placebo-controlled clinical trials are critical to the development of novel treatments for epilepsy, but their design has not changed for decades. Patients, clinicians, regulators, and innovators all have concerns that recruiting for trials ...

    Abstract Well-designed placebo-controlled clinical trials are critical to the development of novel treatments for epilepsy, but their design has not changed for decades. Patients, clinicians, regulators, and innovators all have concerns that recruiting for trials is challenging, in part, due to the static design of maintaining participants for long periods on add-on placebo when there are an increasing number of options for therapy. A traditional trial maintains participants on blinded treatment for a static period (e.g., 12 weeks of maintenance), during which participants on placebo have an elevated risk of sudden unexpected death in epilepsy compared to patients on an active treatment. Time-to-event trials observe participants on blinded treatment until a key event occurs (e.g., post-randomization seizure count matches pre-randomization monthly seizure count). In this article, we review the evidence for these designs based on re-analysis of prior trials, one published trial that used a time-to-second seizure design, and experience from an ongoing blinded trial. We also discuss remaining concerns regarding time-to-event trials. We conclude that, despite potential limitations, time-to-event trials are a potential promising mechanism to make trials more patient friendly and reduce placebo exposure, which are urgent needs to improve safety and increase recruitment to trials.
    MeSH term(s) Humans ; Anticonvulsants/therapeutic use ; Epilepsy/drug therapy ; Epilepsy/chemically induced ; Research Design ; Seizures/drug therapy ; Seizures/chemically induced ; Clinical Trials as Topic
    Chemical Substances Anticonvulsants
    Language English
    Publishing date 2023-05-02
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 216382-2
    ISSN 1528-1167 ; 0013-9580
    ISSN (online) 1528-1167
    ISSN 0013-9580
    DOI 10.1111/epi.17621
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  8. Article ; Online: A phase 1 open-label trial evaluating focused ultrasound unilateral anterior thalamotomy for focal onset epilepsy.

    Krishna, Vibhor / Mindel, Jesse / Sammartino, Francesco / Block, Cady / Dwivedi, Alok Kumar / Van Gompel, Jamie J / Fountain, Nathan / Fisher, Robert

    Epilepsia

    2023  Volume 64, Issue 4, Page(s) 831–842

    Abstract: Objective: Focused ultrasound ablation (FUSA) is an emerging treatment for neurological and psychiatric diseases. We describe the initial experience from a pilot, open-label, single-center clinical trial of unilateral anterior nucleus of the thalamus ( ... ...

    Abstract Objective: Focused ultrasound ablation (FUSA) is an emerging treatment for neurological and psychiatric diseases. We describe the initial experience from a pilot, open-label, single-center clinical trial of unilateral anterior nucleus of the thalamus (ANT) FUSA in patients with treatment-refractory epilepsy.
    Methods: Two adult subjects with treatment-refractory, focal onset epilepsy were recruited. The subjects received ANT FUSA using the Exablate Neuro (Insightec) system. We determined the safety and feasibility (primary outcomes), and changes in seizure frequency (secondary outcome) at 3, 6, and 12 months. Safety was assessed by the absence of side effects, that is, new onset neurological deficits or performance deterioration on neuropsychological testing. Feasibility was defined as the ability to create a lesion within the anterior nucleus. The monthly seizure frequency was compared between baseline and postthalamotomy.
    Results: The patients tolerated the procedure well, without neurological deficits or serious adverse events. One patient experienced a decline in verbal fluency, attention/working memory, and immediate verbal memory. Seizure frequency reduced significantly in both patients; one patient was seizure-free at 12 months, and in the second patient, the frequency reduced from 90-100 seizures per month to 3-6 seizures per month.
    Significance: This is the first known clinical trial to assess the safety, feasibility, and preliminary efficacy of ANT FUSA in adult patients with treatment-refractory focal onset epilepsy.
    MeSH term(s) Adult ; Humans ; Epilepsies, Partial/diagnostic imaging ; Epilepsies, Partial/surgery ; Epilepsies, Partial/drug therapy ; Seizures/drug therapy ; Anterior Thalamic Nuclei ; Attention ; Treatment Outcome
    Language English
    Publishing date 2023-03-01
    Publishing country United States
    Document type Clinical Trial, Phase I ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 216382-2
    ISSN 1528-1167 ; 0013-9580
    ISSN (online) 1528-1167
    ISSN 0013-9580
    DOI 10.1111/epi.17535
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  9. Article ; Online: Multifocal hypometabolic correlates to deficits of verbal memory in mesial temporal lobe epilepsy.

    Smetana, Racheal M / Batchala, Prem P / Lee, Bern G / Albataineh, Tamer / Broshek, Donna K / Fountain, Nathan B / Abbas, Salma / Quigg, Mark

    Epilepsy & behavior : E&B

    2023  Volume 143, Page(s) 109244

    Abstract: Background and objectives: Neuropsychological research on mesial temporal lobe epilepsy (MTLE) often highlights material-specific memory deficits, but a lesion-focused model may not accurately reflect the underlying networks that support episodic memory ...

    Abstract Background and objectives: Neuropsychological research on mesial temporal lobe epilepsy (MTLE) often highlights material-specific memory deficits, but a lesion-focused model may not accurately reflect the underlying networks that support episodic memory in these patients. Our study evaluated the pathophysiology behind verbal learning/memory deficits as revealed by hypometabolism quantified through 18-fluorodeoxyglucose positron emission tomography (FDG-PET).
    Methods: This retrospective study included thirty presurgical patients with intractable unilateral MTLE who underwent interictal FDG-PET and verbal memory assessment (12 females, mean age: 38.73 years). Fluorodeoxyglucose-positron emission tomography mapping was performed with voxel-based mapping of glucose utilization to a database of age-matched controls to derive regional Z-scores. Neuropsychological outcome variables included scores on learning and recall trials of two distinct verbal memory measures validated for use in epilepsy research. Pearson's correlations evaluated relationships between clinical variables and verbal memory. Linear regression was used to relate regional hypometabolism and verbal memory assessment. Post hoc analyses assessed areas of FDG-PET hypometabolism (threshold Z ≤ -1.645 below mean) where verbal memory was impaired.
    Results: Verbal memory deficits correlated with hypometabolism in limbic structures ipsilateral to language dominance but also correlated with hypometabolism in networks involving the ipsilateral perisylvian cortex and contralateral limbic and nonlimbic structures.
    Discussion: We conclude that traditional models of verbal memory may not adequately capture cognitive deficits in a broader sample of patients with MTLE. This study has important implications for epilepsy surgery protocols that use neuropsychological data and FDG-PET to draw conclusions about surgical risks.
    MeSH term(s) Female ; Humans ; Adult ; Epilepsy, Temporal Lobe/complications ; Epilepsy, Temporal Lobe/diagnostic imaging ; Epilepsy, Temporal Lobe/psychology ; Fluorodeoxyglucose F18 ; Retrospective Studies ; Positron-Emission Tomography/methods ; Memory Disorders/diagnostic imaging ; Memory Disorders/etiology ; Memory, Episodic
    Chemical Substances Fluorodeoxyglucose F18 (0Z5B2CJX4D)
    Language English
    Publishing date 2023-05-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2010587-3
    ISSN 1525-5069 ; 1525-5050
    ISSN (online) 1525-5069
    ISSN 1525-5050
    DOI 10.1016/j.yebeh.2023.109244
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  10. Article ; Online: A single-center survey on physical activity barriers, behaviors and preferences in adults with epilepsy.

    Alexander, Halley B / Arnel, Madison / O'Connell, Nathaniel / Munger Clary, Heidi M / Fanning, Jason / Brubaker, Peter / Fountain, Nathan B / Duncan, Pamela

    Epilepsy & behavior : E&B

    2023  Volume 149, Page(s) 109491

    Abstract: Background: Improved understanding of physical activity barriersand preferences in people with epilepsyis needed to successfully design and perform larger, more robust effectivenesstrials.: Methods: Adult patients at a single tertiary epilepsy center ...

    Abstract Background: Improved understanding of physical activity barriersand preferences in people with epilepsyis needed to successfully design and perform larger, more robust effectivenesstrials.
    Methods: Adult patients at a single tertiary epilepsy center between January and April 2020 were surveyed. The survey included a validated physical activity questionnaire (Physical Activity Scale for the Elderly) plus 15 items aimed to address 1) perceptions and beliefs regarding physical activity, 2) barriers to routine physical activity, and 3) willingness and ability to participate in a physical activity intervention and 4) current physical abilities, activities, and preferences.
    Results: 95 participants with epilepsy (age 42 ± 16.2, 59 % female) completed the survey. Sixty-five participants (68.4 %) reported that they believe that physical activity could improve their seizure frequency. However, 40 % of those surveyed said their neurologist had never talked to them about physical activity. The most commonly reported barriers to physical activity were lack of time (24.7 %) and fear of having a seizure (19.7 %), while barriers to intervention participation included being unable to come to in-person sessions (53 % of those willing to participate),living far away (39.3 %), time constraints (28.6 %), and lack of transportation (21.4 %).
    Conclusion: Future physical activity studies in people with epilepsy should focus on using tailored interventions that accommodate their unique beliefs and barriers.
    MeSH term(s) Adult ; Humans ; Female ; Aged ; Male ; Epilepsy ; Seizures ; Exercise ; Surveys and Questionnaires ; Fear
    Language English
    Publishing date 2023-11-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2010587-3
    ISSN 1525-5069 ; 1525-5050
    ISSN (online) 1525-5069
    ISSN 1525-5050
    DOI 10.1016/j.yebeh.2023.109491
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