bluuebunny/crossref_metadata_2025_split huggingface dataset:
GLUT1 Deficiency Syndrome and the Ketogenic Dietary Therapies
Authors: Klepper Joerg 
Published: March 2022

AbstractIn the fed state, the human brain relies entirely on glucose for energy metabolism. Glucose entry into the brain is exclusively mediated by the facilitated glucose transporter protein type 1 (GLUT1). Impaired glucose transport into the brain resulting from GLUT1 deficiency will cause a cerebral “energy crisis,” particularly in the young, because the developing brain requires three to four times more energy than the adult brain. Clinical features of GLUT1 deficiency are global developmental delay, early-onset epilepsy, and a complex movement disorder. In suspected cases, a lumbar puncture should be performed in a metabolic steady state following a 4- to 6-hr fast. In GLUT1 deficiency, cerebrospinal fluid (CSF) glucose concentrations usually are &lt; 50 mg/dl. GLUT1 deficiency is treatable only by means of a ketogenic diet, which provides ketone bodies as an alternative fuel for brain energy metabolism. The majority of patients with GLUT1 deficiency show immediate and continuing seizure control during ketogenic diet treatment.
Ketogenic Diet in Established Epilepsy Indications
Authors: Bergin Ann M. 
Published: March 2022

AbstractThe ketogenic diet (KD) provides an alternative strategy for seizure control in medication-resistant epilepsy. It is particularly valuable for those medication-resistant patients who are not surgical candidates. Years of observational evidence have been recently supported by a randomized controlled study indicating the benefit of diet treatment in children with refractory epilepsy, compared with a control group who delayed diet treatment for 3 months. Well-established uses include children with refractory, nonsurgical epilepsies, as well as epileptic encephalopathies, including infantile spasms and West syndrome, Lennox-Gastaut syndrome, and Dravet and Doose syndromes. The efficacy and role of diet therapy in these conditions are discussed.
Ketogenic Diet Therapy for Infants
Authors: van der Louw Elles J. T. M. , Auvin Stéphane , Cross J. Helen 
Published: March 2022

Abstract
Ketogenic diet therapy (KDT) is a nonpharmacologic treatment for children with pharmacoresistant epilepsy and/or metabolic diseases. For a long time, the KDT was not recommended for use in infancy (children &lt; 2 years old) because this is such a crucial period in development and the risk of nutritional inadequacies was considered too great. To date, side effects in infants are identified, well described, and manageable by close monitoring from a multidisciplinary team. The international consensus guidelines for infants published in 2016 give guidance on how the diet should be administered and in whom, with the aim to set out optimal clinical practice that can be utilized and followed in the care of an infant being treated with KDT. Future prospective intervention studies should focus on fine-tuning the recommendations to the needs of this specific age group, in order to enable them to reach their developmental milestones, to improve cognitive outcomes, and to limit the side effects (e.g., growth retardation) in the longer term. This chapter not only gives an update of the literature and summarizes the recommendations of the international infant guidelines, but also demonstrates some case calculations from clinical practice.
Ketogenic Diet in Status Epilepticus
Authors: Nabbout Rima 
Published: March 2022

Abstract
Overall, 15% of status epilepticus cases admitted to the hospital become super-refractory. In adults, super-refractory status epilepticus has a high mortality rate (&gt; 60%). Although the risk of death is low in the pediatric population, the risk of subsequent neurologic morbidity and cognitive problems is high. The therapeutic intervention aims to reduce its duration, mortality, and short- and long-term comorbidities. The ketogenic diet can be effective: the multiple mechanisms of action of KD, lack of interactions with other drugs, and both enteral and parenteral administration possibilities make it a good choice for refractory status epilepticus. The inherent combination of mechanisms can mimic polytherapy, an approach that is suggested to be a good choice. More research and clinical trials are needed.
Preventing Side Effects and Diet Discontinuation
Authors: Herren Cherie L. , Said Rana R. 
Published: March 2022

Abstract
In general, the ketogenic diet is well tolerated. Common side effects include constipation, vomiting, acidosis, and vitamin/mineral deficiencies. More significant side effects are rare, but include pancreatitis, hepatitis, kidney stones, and cardiomyopathy. During initiation, transient side effects can include dehydration, hypoglycemia, acidosis, vomiting, and refusal to eat. There are many reasons for ketogenic diet discontinuation, the most common being lack of efficacy after 3 to 6 months, or if seizures worsen. After 2 years of a patient’s effective use of the KD, most neurologists would consider discontinuation. The typical approach is a gradually lowering of the ratio of fat to protein and carbohydrate, then relaxing the weighing of ingredients, and finally adding new carbohydrate foods while keeping calories constant. This is followed by relaxation of calorie restriction and then gradual introduction of carbohydrate-containing foods. Approximately 80% of children will remain seizure-free when tapered off the KD if they have completely responded to diet therapy and are medication-free.
Ketogenic Diet, Social Behavior, and Autism
Authors: Cheng Ning , Masino Susan A. , Rho Jong M. 
Published: March 2022

Abstract
The ketogenic diet (KD) is a metabolism-based therapy. There have been promising results from both patients and animal models of autism spectrum disorder (ASD) treated with the KD, indicating that it could afford beneficial effects in this disease. Notably, abundant evidence from animal models suggests that the KD improves social interaction and communication, which are hallmark areas affected in ASD. This is not entirely surprising, because metabolic dysregulation is hypothesized to play a critical pathophysiologic role. However, the mechanisms accounting for the effects of the KD on social behavior remain largely unknown. This chapter reviews the recent evidence regarding use of the KD in the treatment of autism, especially with respect to socialization functions, and discusses the future directions for this line of research.
Ketogenic Diets and Neuroinflammation
Authors: Ruskin David , Dupuis Nina , Auvin Stéphane 
Published: March 2022

AbstractThe high-fat, low-carbohydrate ketogenic diet (KD) is an established and proven treatment for pharmacoresistant epilepsy. Recently, the KD has been validated as a treatment option for some inflammation-induced epileptic encephalopathies. Given the broad neuroprotective properties of the KD in various experimental models of neurologic disorders, there are emerging potential future applications. Indeed, there is growing clinical and basic laboratory evidence that the KD exerts anti-inflammatory effects. Ketone bodies, caloric restriction, and polyunsaturated fatty acids—among other substrates and mediators—might be involved in the modulation of inflammation by the KD. This chapter reviews the evidence that, in part through anti-inflammatory effects, the KD holds promise in the treatment of certain epileptic disorders, neuropathic pain, multiple sclerosis, and Parkinson’s disease.
The Ketogenic Diet in the Treatment of Schizophrenia
Authors: Sarnyai Zoltán , Kraeuter Ann-Katrin , Palmer Christopher M. 
Published: March 2022

Abstract
Evidence is emerging that supports the use of ketogenic dietary intervention in the treatment of schizophrenia and other chronic psychotic disorders. The cause of schizophrenia is unknown. Current theories include the dopamine hypothesis and the view that schizophrenia is a neurodevelopmental disorder. Emerging evidence suggests that bioenergetics and mitochondrial dysfunction may play a role. Long-standing clinical and epidemiologic observations have found high prevalence rates of obesity, diabetes, cardiovascular disease, and premature mortality in people with schizophrenia, suggesting a connection with metabolic disorders. The ketogenic diet is a metabolic intervention that may improve bioenergetic deficiencies in the brains of people with schizophrenia, resulting in improvement of clinical symptoms. Basic science, animal, and human studies are reviewed and synthesized in order to explore this exciting and emerging field.
Ketogenic Diet and Adenosine in Epilepsy
Authors: Kawamura Masahito 
Published: March 2022

AbstractIn recent decades, several mechanisms have been reported to underlie the anticonvulsant effects of the ketogenic diet (KD). These mechanisms were found by using in vivo and in vitro animal models. This chapter reviews in vivo and in vitro approaches for investigating antiseizure mechanisms of the KD. In vivo animal models have been used with three types of seizure models: (1) electrical shock-induced seizure models, (2) drug-induced seizure models, and (3) genetically modified seizure models. In vitro animal models have been used by reproducing conditions of the KD: direct application of ketone bodies and hippocampal slices from KD-fed animals. Both can be used successfully for investigating the KD’s mechanisms. The discussion also focuses on adenosine-based mechanisms of antiseizure effects found by using in vivo and in vitro animal models. Adenosine might be one of the key mechanisms of the anticonvulsant effects of the KD.
Ketogenic Diet, Aging, and Neurodegeneration
Authors: Xu Kui , Sethuraman Aarti , LaManna Joseph C. , Puchowicz Michelle A. 
Published: March 2022

AbstractThe brain, unlike other organs, is normally completely dependent on glucose, but is capable of using ketones as an alternate energy source, as occurs with prolonged starvation or chronic feeding of a ketogenic diet (high fat, low carbohydrate). Over the past decade, research has consistently shown that ketosis is neuroprotective against ischemic insults in rodents. This chapter focuses on investigation of the mechanistic links to neuroprotection by ketosis in the aged. Recovery from stroke and other pathophysiologic conditions in the aged is challenging. Cerebral metabolic rate for glucose (CMRglu), cerebral blood flow (CBF), and/or the defenses against oxidative stress are known to decline with age, suggesting dysfunction of the neurovascular unit. One mechanism of neuroprotection by ketosis involves succinate-induced stabilization of hypoxia-inducible factor 1α (HIF-1α) and its downstream effects on intermediary metabolism. It is possible that ketone bodies play a role in the restoration of energy balance (stabilization of ATP supply), as well as act as signaling molecules, through the upregulation of anti-inflammatory and prosurvival pathways targeted by HIF-1α.
Metabolic Seizure Resistance via BAD and KATP Channels
Authors: Martínez-François Juan Ramón , Danial Nika , Yellen Gary 
Published: March 2022

Abstract
Ketogenic diets are a very effective treatment for epilepsy. On a ketogenic diet, ketone bodies provide an alternative brain fuel, replacing much of the glucose ordinarily used by the brain. This change in fuel utilization may alter neuronal excitability and help produce the anticonvulsant effect of the diet. Brain fuel utilization can also be modified by a nondietary approach: genetic alteration of the protein BAD, which has known roles in regulating both apoptosis and glucose metabolism. When the metabolic function of BAD is genetically altered in mice, it produces reduced glucose metabolism and increased ketone body metabolism in neurons and astrocytes. This effect is related to regulation of BAD by phosphorylation and is independent of its apoptotic function. Mice with BAD modifications that produce a decrease in glucose metabolism exhibit strong resistance to behavioral and electrographic seizures in vivo. At the cellular level, BAD alteration leads to decreased seizurelike activity in the entorhinal cortex and hippocampus, two brain areas critical for seizure generation and propagation. BAD’s seizure protective effect is lost upon selective deletion of ATP-sensitive potassium (KATP) channels in the dentate gyrus, suggesting that KATP channels in this brain region may mediate BAD’s anticonvulsant effect.
Lactate Dehydrogenase
Authors: Sada Nagisa , Inoue Tsuyoshi 
Published: March 2022

Abstract
Glucose is transported into neurons and is used as an energy source. It is also transported into astrocytes and is converted to lactate, which is then released to neurons and is used as another energy source. The latter is called the astrocyte–neuron lactate shuttle. The lactate shuttle is a metabolic pathway, but it also plays important roles in neuronal activities and brain functions. Our studies have revealed that lactate dehydrogenase (LDH), a metabolic enzyme in the lactate shuttle, is involved in epilepsy and the ketogenic diet. Interestingly, LDH is inhibited by stiripentol, a clinically used antiepileptic drug for Dravet syndrome. This chapter provides an overview of electrical regulation by the ketogenic diet and astrocyte–neuron lactate shuttle, and then introduces LDH as a metabolic target in epilepsy.
Amino Acids in the Treatment of Neurologic Disorders
Authors: Hartman Adam L. 
Published: March 2022

Abstract
Studies of metabolism- and diet-based therapies in the acute treatment of neurologic disorders and neuroprotection have focused primarily on the quality and quantity of fat supplementation or carbohydrate restriction. However, protein is another key dietary component that is underappreciated and understudied. Several amino acids have been shown to stop, terminate, or prevent seizures. In addition, some have been shown to exert neuroprotective effects in other neurologic disorders. Amino acids (and their metabolites) may exert their effects by acting at membrane or cytoplasmic receptors, by serving as substrates for membrane transporters, and by acting as modulators of signaling pathway activity. This chapter highlights examples of each of these mechanisms of action in select nervous system disorders.
Triheptanoin in Epilepsy and Beyond
Authors: Borges Karin 
Published: March 2022

AbstractTriheptanoin, the triglyceride of heptanoate (C7 fatty acid), is a novel treatment that is being used to treat patients with rare genetic metabolic disorders. In the gastrointestinal tract, triheptanoin is hydrolyzed to heptanoate, which diffuses into the blood and the rest of the body. Within mitochondria, heptanoate and its liver ketone metabolites are then metabolized to acetyl-CoA and propionyl-CoA. After carboxylation, the latter becomes succinyl-CoA, which can be anaplerotic—refilling a deficient tricarboxylic acid (TCA) cycle. Here, data are summarized and discussed in relation to triheptanoin’s anticonvulsant effects in rodent seizure models and clinical trials. Clinical improvements in people with long-chain fatty acid oxidation deficiencies were mostly reported with regard to cardiac dysfunction and are summarized. Moreover, there are increasing preclinical and clinical studies indicating that triheptanoin can be antioxidant and sometimes beneficial in other neurologic and neuromuscular disorders, which are also summarized here. In general, triheptanoin treatment appears to be safe. Tolerability can be an issue due to gastrointestinal side effects, such as diarrhea, bloating, and nausea, which often can be managed with smaller, more frequent doses of triheptanoin and mixing it with food. However, despite its efficacy in long-chain fatty acid oxidation deficiencies, beneficial effects of triheptanoin in neurologic conditions appear to be limited. In summary, triheptanoin is safe and promising for a variety of conditions, and it is now important to identify the disorders that respond to this anaplerotic treatment.
Social Work and Palliative Care—The Early History
Authors: Saunders Dame Cicely 
Published: March 2022

Abstract
This historic reprint of an article written by Dame Cicely Saunders for the British Journal of Social Work was adapted from a talk given in 2000 to the Annual General Meeting of the Association of Hospice and Palliative Care Social Workers. It was also published in the Oxford Textbook of Palliative Social Work (2011), edited by Altilio and Otis-Green, as it highlights the influence of Saunders’ social work background in her development of the concept of “total pain,” which recognizes the need to assess and address the multidimensional aspects of human suffering if we are to improve quality of life for those facing end of life.
Social Work in Pediatric Palliative Care
Authors: Jones Barbara L. , Remke Stacy S. , Carnahan-Metzger Rachel , Phillips Farya 
Published: March 2022

Abstract
Social workers have long been integral to efforts to improve care for children and their families along the continuum of illness and strive to address the unique needs of children with serious illness. Pediatric palliative social workers are often in a position to assist families in identifying and addressing their greatest concerns at a time of overwhelming stress, identifying the psychosocial, social justice, and family systems variables that influence and inform their responses and needs. The social work skill sets that include person-in-context assessment, therapeutic counseling, interpersonal skills, group facilitation, and systems knowledge are of great value in pediatric palliative care teams.
Adolescents and Young Adults Living with Serious Illness
Authors: Cheung Christabel K. , Wiener Lori 
Published: March 2022

Abstract
Adolescents and young adults (AYAs) living with serious illness are uniquely challenged by the conundrum of possessing the cognitive capacity to understand the gravity of their illness, yet lacking skills to cope with that understanding. They are tasked with navigating transitions from childhood to adulthood that are already characterized by tremendous growth, change, and heightened vulnerability to stress. AYAs benefit from early introduction of an integrated approach to palliative social work—combining knowledge and strategies from pediatric and adult settings, with uniquely AYA interventions that reflect their sociodemographic and contextual complexity. In this chapter, we define and characterize the AYA patient care population; describe the significance of palliative social work; highlight clinical strategies and skills for working with AYAs; detail a developmentally appropriate approach to advance care planning; and conclude by discussing self-care practices for palliative social workers interested in sustaining a rewarding career, infused with personal and professional growth.
Beyond Vulnerability
Authors: Gehlert Sarah , Moro Teresa 
Published: March 2022

Abstract
Living with chronic and serious illness confers vulnerability for many at the time of diagnosis and for some throughout the course of the illness as functional abilities decline. Individuals with disabilities often experience worse health and more systemic barriers to accessing quality healthcare than members of the general population. In addition, many individuals with disabilities experience healthcare disparities and engage with systems ill equipped to provide them with quality healthcare. In the United States, individuals with disabilities are often underserved and are without healthcare insurance coverage, access to quality palliative care services, and the ability to pay for needed services. Social workers will engage with individuals with these and other conditions in a variety of settings and need to be prepared to adapt their practice approach based on their individual needs and advocate for policy and systems of care that maximize agency and enhance access to care.
Dying in a Foreign Land
Authors: Carrion Iraida V. 
Published: March 2022

Abstract
Identifying diversity among immigrants in the palliative care setting is essential. It is vital to understand the country of origin and to have an understanding of the country’s regions, customs, specific characteristics, and geographical features that facilitates engagement and interventions with immigrants and their families. The ability to identify language preferences, religious/spiritual beliefs, and health beliefs during serious illness and at the end of their lives enables communication regarding treatment decisions. Social workers need to inform patients and their family members that they will maintain their confidentiality with regard to immigration status issues. Recognizing, validating, and exploring beliefs related to truth telling is important in serious illness and end-of-life care. Additionally, immigrants’ requests for palliative treatment and their wishes concerning the place of death and burial must be proactively assessed in the context of serious illness and its impact on mixed-status families.
Palliative Social Work and Heart Failure
Authors: O’Donnell Arden , Ng Tracy 
Published: March 2022

Abstract
Heart failure affects the lives of millions of Americans each year and results in significant physical and psychological stressors that can negatively impact quality of life. Palliative social workers possess unique skills that can benefit patients living with heart failure by supporting increased understanding of disease and its trajectory and enhancing communication with other clinicians, as well as maximizing quality of life. This chapter provides basic education and explores common interventions used to support this patient population. Key interventions include in-depth psychosocial assessment, facilitating goals of care conversations, and addressing patient-centered concerns commonly arising as patients navigate complex decision-making that sometimes accompany this disease.
Clinical Trials and the Role of Social Work
Authors: BrintzenhofeSzoc Karlynn 
Published: March 2022

Abstract
Increasing the role of palliative social workers in clinical trials can improve quality of life, access to good medical care, and access to state of the art treatments. In order for social workers to have a role on clinical trial multidisciplinary teams, their knowledge base needs to include many aspects of clinical trials. This chapter includes an introduction to this knowledge. It also offers ways social workers can add value to clinical trial multidisciplinary teams in terms of helping to improve recruitment of participants (e.g., improve diversity of participants through advocacy, ensuring participants are fully informed about the decision to join or withdraw from a study). This improvement will come from bringing expertise on minimizing social injustice issues and providing psychosocial support to the team and the participants.