bluuebunny/crossref_metadata_2025 huggingface dataset:
Refractory Chronic Migraine
Authors: Newman Lawrence C. , Levin Morris , Halker Singh Rashmi B. , Michael Rebecca L.
Published: March 2022

This chapter discusses refractory chronic migraine (CM), which is defined as ≥15 headache days/month for more than 3 months and on at least 8 days/month the headache has the features of migraine headache. CM has been shown to cause greater headache-related disability, headache impact, societal burden, and lower quality of life scores compared with episodic migraine. In general, all patients with CM require preventive therapy; only onabotulinumtoxinA (OBTA) is approved for the prevention of CM. Many patients receiving treatment with OBTA experience a “wearing off” of the beneficial effects before their next dose is due, often within the past 2 weeks. Increasing the OBTA dose from 155 units to 195 units or redosing at 10 rather than 12 weeks may prevent wear-off. Meanwhile, bridge therapies include occipital nerve or sphenopalatine nerve blocks at the 10-week mark. Adding oral preventive medications or injectable calcitonin gene-related peptide monoclonal antibodies to the OBTA may reduce migraine attacks.
High-Altitude Headache
Authors: Newman Lawrence C. , Levin Morris , Halker Singh Rashmi B. , Michael Rebecca L.
Published: March 2022

High-altitude headache (HAH) is classified as a disorder of homeostasis. It tends to occur when ascending altitudes higher than 2500 m and resolves within 24 hours of descending to less than 2500 m. More than 30% of mountaineers will experience a headache at elevations, particularly with rapid ascent and at very high altitudes. HAH can accompany acute mountain sickness, with other symptoms part of this syndrome being nausea, fatigue, dizziness, loss of appetite, dyspnea, and sleep disturbance. This chapter defines the etiology of HAH as well as the related problem of acute mountain sickness. Readers are provided with an understanding of the pathophysiology of HAH, as well as practical management options.
Headache Treatment in Depression and Anxiety
Authors: Newman Lawrence C. , Levin Morris , Halker Singh Rashmi B. , Michael Rebecca L.
Published: March 2022

This chapter discusses headache treatment in depression and anxiety. The most common mood disorders seen in headache patients include depression, anxiety, and bipolar disorder. It is crucial to screen for psychiatric comorbidities in all headache patients because these seem to increase the risk of development of headache chronicity, decrease quality of life, and complicate management. Of utmost importance is to recognize a patient who may be at risk for harm to themself or others. Suicide attempts seem to be more frequent in patients suffering from migraine than in the general population, especially in women and in those who have migraine with aura. As such, it is important that clinicians have a clear strategy for dealing with a suicidal patient. Although monotherapy for mood disorder and migraine can be considered for mild cases, often a collaborative approach with psychiatry is necessary to ensure both psychiatric disease and headache are adequately managed.
Menstrual Headaches
Authors: Newman Lawrence C. , Levin Morris , Halker Singh Rashmi B. , Michael Rebecca L.
Published: March 2022

This chapter discusses menstrually related migraine (MRM), which are typical from 2 days prior to the onset of menses to the third day of flow. The majority of women with migraine, in fact, experience MRM. The headaches are generally not associated with auras, for unclear reasons. The two main proposed pathophysiological mechanisms of MRM are a drop in estrogen blood levels and prostaglandin release. Many women report that their menstrual migraines are more severe, disabling, and refractory to treatment compared to migraines at other times of the month. Focused “miniprophylaxis” treatments during the perimenstrual period can be very successful, but acute treatments are generally necessary as well, including triptans. Estrogenic agents are contraindicated in younger women who have migraine with aura because of postulated increased stroke risks, although their use can sometimes be justified if low doses are used and other risk factors are minimized.
Headache in the Elderly
Authors: Newman Lawrence C. , Levin Morris , Halker Singh Rashmi B. , Michael Rebecca L.
Published: March 2022

In the United States, people older than age 65 years comprise the fastest growing segment of the population. Migraine is typically thought of as a disease of young people, and although it is true that migraine rarely has its onset after age 50 years and that many individuals with migraine report that their headaches improve as they grow older, the prevalence of migraine in the elderly is significant. Estimates suggest that 3–10% of those older than age 65 years suffer from migraine, report migraine-related disability, and require treatment. This chapter summarizes the differential diagnosis of headaches in the older patient population and also discusses considerations when selecting acute migraine treatment for older patients. Although many patients have contraindications to triptan therapy, new acute treatments including gepants and lasmiditan are now available for patients who previously had limited options.
Recurring Headaches in Medication-Averse Patients
Authors: Newman Lawrence C. , Levin Morris , Halker Singh Rashmi B. , Michael Rebecca L.
Published: March 2022

This chapter discusses recurring headaches in medication-averse patients. When patients are averse to pharmaceutical intervention, it is worthwhile exploring their reasons, many of which are quite valid, including previous intolerable adverse effects. Overaggressive attempts to alter their preferences might be counterproductive, leading to a lack of trust and poor compliance. On the other hand, listening to their specific concerns and addressing them when possible might set the stage for introducing low-risk and well-tolerated medication, perhaps starting with very low dosages, in conjunction with nonpharmaceutical measures. These options include nutriceuticals, behavioral treatments, electrical and magnetic stimulation, and physical techniques such as massage.
COVID-19 Cephalalgia
Authors: Newman Lawrence C. , Levin Morris , Halker Singh Rashmi B. , Michael Rebecca L.
Published: March 2022

This chapter assesses COVID-19 cephalalgia. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus can attack essentially any part of the nervous system; central nervous system manifestations include headache, meningitis, encephalitis, seizures, and stroke. Headaches are reported in as many as 40% of those affected by the SARS-CoV-2 virus and are usually resistant to analgesics. COVID-19–related headaches may be caused by activation of the trigeminal–vascular pathways by viral entry into the brain through the olfactory bulb, direct viral infection across the blood–brain barrier, or as the result of the cytokine storm that follows SARS-CoV-2 infection. The headache of COVID-19 may have characteristics that resemble migraine or be nonspecific like other headaches associated with systemic viral infections. If abnormalities are found on the neurological exam, a workup for sinister causes of headaches must be undertaken.
Introduction
Authors: Holzer Jacob C. , Dew Andrea J. , Recupero Patricia R. , Gill Paul
Published: March 2022

Lone-actor terrorism is a complex, multidimensional process involving different contexts, ideologies, geographic regions, circumstances, drives, individuals, and modes of violence. Important concepts reviewed in the chapters of this volume include clinical and behavioral variables, developmental aspects, the role of rhetoric and the internet, the influence of organized groups on the individual, geographic differences, legal issues, forensic mental health assessments, ethical considerations, and the role of law enforcement at the federal, state, and local levels, among several other variables. A better understanding of these variables may allow for a better appreciation of the etiology of lone-actor terrorism and its impact on society.
Clinical Psychiatric and Neuropsychiatric Aspects of Lone-Actor Terrorism
Authors: Granacher Robert P. , Kushner Danielle B. , Holzer Jacob C.
Published: March 2022

Individuals who engage in violence defined as “lone-actor terrorism” vary widely—in background, ideology, and the etiological “drive” of their behavior, methodology, and geographic site of the index incident. In addition to these factors, clinical variables are present in at least some if not most cases. These variables include clinical conditions such as schizophrenia, mood and anxiety disorders, personality disorders, traumatic brain injuries, autistic spectrum disorders and substance abuse, adjustment difficulties, and psychological trauma. This chapter reviews two important areas: the first section explores a limited number of cases with respect to clinical aspects to highlight the variance in clinical aspects, and the second section reviews different mechanisms, as found in some conditions, which may be relevant in individual cases of lone-actor terrorism.
The Role of Psychometrics in Investigating Lone-Actor Terrorism
Authors: Moczynski Nancy P. , Schiller Allen R. , Farah Theodora Najla , Drogin Eric Y.
Published: March 2022

There exists no universally recognized profile for the “terrorist personality.” Researchers continue to investigate relevant psychological constructs for lone-actor terrorists in an attempt to provide a scientifically informed basis for predicting vulnerability to radicalization and risk for subsequent acts of violence. While documentation of psychometrically based evaluations of lone-actor terrorists has proved exceptionally difficult to obtain, results obtained primarily from open sources suggest that certain emotional, behavioral, and other correlates are increasingly identifiable in this population. In particular, such conditions and situations as depressive disorders; narcissism; extreme, overvalued beliefs; deficits in social cognition; psychosis; and thwarted personal goals continue to surface as potentially relevant factors. This chapter examines the current state of psychometrics in relation to lone-actor terrorism with attention to key diagnostic entities, psychological evaluation methodologies, proven psychometric instruments, the interference of deception and lack of effort, and prospects for the further development of targeted assessment protocols.
Understanding Lone-Actor Violence Through Linguistic Analysis
Authors: Vegt Isabelle W. J. van der , Kleinberg Bennett , Gill Paul
Published: March 2022

This chapter seeks to understand lone-actor terrorists through their use of language. Studies examining terrorist and extremist online postings, pre-attack threats, and manifestos are described. The authors specifically focus on efforts in which linguistic analysis is performed automatically, for example, to measure potential warning signs of violence in text. Following this overview, the authors identify shortcomings to the current approach and provide suggestions on how to further improve our understanding of lone-actor terrorism through language. The increased importance of detecting and countering the narratives of potentially violent individuals online further necessitates focusing on automated approaches to linguistic analysis. They conclude that openness and collaboration between security professionals and researchers is needed to effectively detect and counter terrorist and extremist narratives.
Means, Mechanisms, and Trends of Operationalizing Violence
Authors: Winter Christopher , Spaaij Ramón , Price Marilyn
Published: March 2022

Lone-actor terrorists have utilized a diverse range of weapons to conduct their attacks, ranging from simple melee weapons to firearms (both legal and illegal), vehicles, and explosives. A lone actor terrorist’s choice of weapon is influenced by prior examples of a weapon being used but also, crucially, by that weapon’s availability, a factor that is constrained by the societal and legal frameworks the lone actor terrorist operates in. This is particularly evident with firearms, with more permissive gun control regimes often allowing for easier access to semi-automatic rifles. The use of these weapons has become particularly evident in the United States after the expiry of the Federal Assault Weapons Ban in 2004. As a result, and in the absence of significant legislative change, semi-automatic rifles have become the weapon of choice for lone-actor terrorists in the US.
Lone-Actor Terrorism
Authors: Hassan Steven , Caven-Atack Jon , Shah Mansi J. , Malhotra Simran
Published: March 2022

.This chapter explores the social-psychological forces that destructive/authoritarian cults use as they apply to lone-actor terrorists influenced online. The authors contrast the methods used by authoritarian religious, political, commercial, and therapy groups to show that virtual sources—most notably the World Wide Web—can replace in-person recruitment and inclusion. These lone-actor terrorists adopted a worldview and became part of a virtual society. This virtual social bond can be as powerful as a real social bond. The authors consider case examples to show the dynamics of exploitative persuasion in the build-up to their violence. The BITE model of authoritarian control and influence continuum are presented as ways to evaluate undue influence.
Threat Assessment
Authors: Meloy J. Reid , Holzer Jacob C.
Published: March 2022

In this chapter, the authors present the theoretical model and empirical measurement of the Terrorist Radicalization Assessment Protocol (TRAP-18), a structured professional judgment instrument for those engaged in risk assessment of persons of concern for acts of terroristic violence. The instrument demonstrates both interrater reliability and content, criterion, discriminant, and postdictive validity in a number of studies to date. The TRAP-18 is then used to analyze the case of Timothy McVeigh, a white ethnic nationalist who carried out an act of domestic terrorism in Oklahoma City in 1995, claiming the lives of 168 men, women, and children.
Developing a Risk Assessment and Intervention Strategy
Authors: Holzer Jacob C. , Dew Andrea J. , Recupero Patricia R. , Gill Paul
Published: March 2022

The goal of this volume is to present a comprehensive approach to the complex, multifaceted concept of lone-actor terrorism by spanning a number of different perspectives, including historic, clinical, law enforcement, intelligence, legal, ethical, geographic, use of social media, and propaganda, among other areas. Two interceding events during the writing of this book—the COVID pandemic and the Washington, DC, Capitol insurrection, have implications for the risk of terrorism. The authors propose number of different practical interventions and areas of research that can be considered for the potential to reduce lone-actor terrorism risk to society.
Case 3
Authors: Burri Haran , Johansen Jens Brock , Linker Nicholas J. , Theuns Dominic
Published: March 2022

A patient implanted with a dual-chamber PM for sinus dysfunction was followed up. He was asymptomatic.
Case 4
Authors: Burri Haran , Johansen Jens Brock , Linker Nicholas J. , Theuns Dominic
Published: March 2022

A patient implanted with a DDD PM for sinus dysfunction complained of palpitations. A Holter recording was performed.
Case 12
Authors: Burri Haran , Johansen Jens Brock , Linker Nicholas J. , Theuns Dominic
Published: March 2022

A 45-year-old man presented to the emergency room with several episodes of presyncope. The majority of these were unprovoked episodes, but he was able to reproduce his symptoms by leaning forwards. He had a dual-chamber PM implanted 9 years previously following iatrogenic AVB during ablation for atrioventricular nodal reciprocating tachycardia. He was otherwise fit and well.
Case 16
Authors: Burri Haran , Johansen Jens Brock , Linker Nicholas J. , Theuns Dominic
Published: March 2022

A capture threshold test was performed in a patient in chronic AF awaiting AVN ablation. His lead had been implanted and was connected to the atrial port, with a backup RV lead connected to the ventricular port.
Case 17
Authors: Burri Haran , Johansen Jens Brock , Linker Nicholas J. , Theuns Dominic
Published: March 2022

A 12-lead ECG was recorded in a patient with HBP during a capture threshold test.
Case 20
Authors: Burri Haran , Johansen Jens Brock , Linker Nicholas J. , Theuns Dominic
Published: March 2022

A patient with paroxysmal AVB was implanted with a PM with HBP.
Case 22
Authors: Burri Haran , Johansen Jens Brock , Linker Nicholas J. , Theuns Dominic
Published: March 2022

A capture threshold test was performed in a patient with AVB and a DDD PM with an atrial lead and a His lead connected to the ventricular port.
Case 24
Authors: Burri Haran , Johansen Jens Brock , Linker Nicholas J. , Theuns Dominic
Published: March 2022

A patient with infranodal 2:1 AVB was implanted with a dual-chamber PM with an atrial lead and a left bundle branch area pacing lead.
Case 26
Authors: Burri Haran , Johansen Jens Brock , Linker Nicholas J. , Theuns Dominic
Published: March 2022

An 80-year-old patient received a leadless VVI PM for chronic AF with slow ventricular rate and intermittent dizziness. This device was preferred to a standard PM due to mechanical issues at both shoulders.
Case 29
Authors: Burri Haran , Johansen Jens Brock , Linker Nicholas J. , Theuns Dominic
Published: March 2022

A 52-year-old female attended the device clinic for follow-up. She had a dual-chamber ICD implanted for secondary prevention due to non-ischaemic dilated cardiomyopathy with sustained VT.
Case 31
Authors: Burri Haran , Johansen Jens Brock , Linker Nicholas J. , Theuns Dominic
Published: March 2022

A patient with dilated cardiomyopathy with a history of sustained VT had a dual-chamber ICD implanted at another centre for secondary prevention.
Case 33
Authors: Burri Haran , Johansen Jens Brock , Linker Nicholas J. , Theuns Dominic
Published: March 2022

A patient with ischaemic heart disease and a history of sustained VT had been implanted 3 days ago with a dual-chamber ICD. He consulted for malaise with two shocks.
Case 34
Authors: Burri Haran , Johansen Jens Brock , Linker Nicholas J. , Theuns Dominic
Published: March 2022

A patient with a DDD ICD presented for follow-up. He complained of palpitations and dizziness.
Case 38
Authors: Burri Haran , Johansen Jens Brock , Linker Nicholas J. , Theuns Dominic
Published: March 2022

A patient with a CRT-D was seen at follow-up. The patient had no complaints. Biventricular pacing was delivered in 96% of the time, with 4% VS events.
Case 45
Authors: Burri Haran , Johansen Jens Brock , Linker Nicholas J. , Theuns Dominic
Published: March 2022

A 29-year-old man, implanted with an S-ICD for secondary prevention of sudden death, presented for routine follow-up with several bouts of dizziness and palpitations.
Case 52
Authors: Burri Haran , Johansen Jens Brock , Linker Nicholas J. , Theuns Dominic
Published: March 2022

A 50-year-old woman who had been implanted 5 years ago with a CRT-D, and had normalized her ejection fraction, presented at follow-up without any complaints.
Case 55
Authors: Burri Haran , Johansen Jens Brock , Linker Nicholas J. , Theuns Dominic
Published: March 2022

A patient with a CRT-D was seen at follow-up. The patient did not have any complaints. Biventricular pacing was delivered in 97% of the time, with 3% VS events. There were no VT/VF episodes (VT monitor zone 150–188 bpm, fast VT zone 188–240 bpm, VF zone >240 bpm).
Case 61
Authors: Burri Haran , Johansen Jens Brock , Linker Nicholas J. , Theuns Dominic
Published: March 2022

A 66-year-old man with a cardiac resynchronization defibrillator for secondary prevention of sudden cardiac death presented for routine follow-up. He had no complaints.
Case 63
Authors: Burri Haran , Johansen Jens Brock , Linker Nicholas J. , Theuns Dominic
Published: March 2022

A patient with dilated cardiomyopathy was implanted with a CRT-D. He presented with dyspnoea. The device memory indicated 88% biventricular pacing.
Case 64
Authors: Burri Haran , Johansen Jens Brock , Linker Nicholas J. , Theuns Dominic
Published: March 2022

During remote follow-up, a low percentage of CRT pacing was reported in a patient with a CRT-D device.
Case 69
Authors: Burri Haran , Johansen Jens Brock , Linker Nicholas J. , Theuns Dominic
Published: March 2022

A 60-year-old man presented to the pacing department for a routine device check 6 months following an implant of a primary prevention CRT-D. This was implanted for persisting severe LV systolic dysfunction due to aortic regurgitation, treated with a mechanical aortic valve replacement. He had NYHA class III dyspnoea and LBBB.
Case 70
Authors: Burri Haran , Johansen Jens Brock , Linker Nicholas J. , Theuns Dominic
Published: March 2022

A patient implanted with a CRT-D underwent repositioning of a dislodged coronary sinus lead.
Abortion exceptionalism and the law in the United Kingdom and United States
Authors: Parsons Jordan A. , Romanis Elizabeth Chloe
Published: March 2022

In this chapter, we outline the legal frameworks that govern abortion provision in the UK (including Great Britain and Northern Ireland) and the US. We argue that abortion is ‘exceptionalised’ within these frameworks such that abortion care in both jurisdictions is distinguished from other aspects of healthcare. This ‘abortion exceptionalism’, which is the use of unique rules to place limitations on why, where, and how abortion care can be provided, has the effect of labelling abortion care as ‘nonessential’, even though abortion is increasingly being appropriately recognised as essential healthcare. This has resulted in abortion being subject to increased regulation, supervision, and limitations on decision-making.
Piecemeal progression and home use of misoprostol in the United Kingdom
Authors: Parsons Jordan A. , Romanis Elizabeth Chloe
Published: March 2022

In this chapter, we detail the chain reaction of approving home use of misoprostol for the purposes of early medical abortion that took place throughout the UK over a four-year period, beginning in 2017. Home use of misoprostol can, in many ways, be considered a stepping-stone to the approval of home use of mifepristone. This has been the case in Great Britain. Observing the steps that led to the introduction of home use of misoprostol, we highlight three important procedural aspects of abortion policy in Great Britain (and, to a lesser extent, Northern Ireland): (i) that this policy development can be considered, at best, evidence informed rather than evidence based, (ii) that a highly political use of the precautionary principle is employed, and (iii) that the individual nations of Great Britain have a tendency to stay within arm’s reach of each other on abortion policy.
A telemedical continuum for early medical abortion
Authors: Parsons Jordan A. , Romanis Elizabeth Chloe
Published: March 2022

In this chapter, we argue that it is important to recognise telemedical care pathways in the provision of early medical abortion as existing on a continuum. Various service models already exist, ranging from the simple addition of videoconferencing to allow satellite clinics to provide in-person care to the complete absence of face-to-face contact in the care pathway. There are, then, several tried and tested care pathways. This range should not only be recognised as the reality of existing provision but should be embraced for the purposes of intra-service options. Where feasible, providers should offer patients options at each stage of the care pathway, allowing them to choose a mixture of in-person and telemedical elements in line with their subjective values and preferences. This ultimately enhances patient autonomy and furthers patient-centred care.
The necessity of telemedical abortion during a pandemic
Authors: Parsons Jordan A. , Romanis Elizabeth Chloe
Published: March 2022

In this chapter, we demonstrate the importance of service model changes to abortion care to continue to meet the demand for abortion during the COVID-19 pandemic. We consider the necessity and importance of availability of abortion in the circumstances, and how existing socio-legal barriers to care in the UK and US were exacerbated by the pandemic. We suggest that in the circumstances, changes to allow home use of mifepristone—and consequently to enable the lawful provision of telemedical abortion—were necessary and a human rights imperative to ensure access to abortion. As well as highlighting the demonstrable need for telemedical provision of early medical abortion and how it can resolve access problems that are exacerbated in the context, we make legal arguments for the necessity of its provision—appealing to human rights jurisprudence in the context of the UK, and the Constitution in the US.
The legal and policy response to abortion care in the United Kingdom during COVID-19
Authors: Parsons Jordan A. , Romanis Elizabeth Chloe
Published: March 2022

In this chapter, we consider the changes to abortion law introduced in Great Britain in March 2020 in response to access concerns related to the COVID-19 pandemic. These changes allowed, for the first time in Great Britain, home use of mifepristone. This meant people could access abortion entirely remotely, and thus safely, from their homes. Before these changes, remote abortion care was unlawful because it was not lawful for persons to receive abortion medications without attending a clinic nor for them to administer mifepristone at home. This chapter outlines how these changes came to fruition, the substantive detail of the changes, and what they mean for abortion care in Great Britain. We also consider why these changes have not been made, and the impact of this, in Northern Ireland. We argue that these changes to the law should be made permanent in order to address socio-legal barriers to care.
Alternative Ketogenic Diets
Authors: Neal Elizabeth
Published: March 2022

As the classic ketogenic diet celebrates its centennial anniversary, the wider ketogenic landscape has expanded considerably both in application and implementation. As less restrictive dietary approaches have been developed, including the low-glycemic-index treatment and the modified Atkins diet, these approaches are now being used worldwide. The advantages of a more liberal ketogenic diet have been recognized, especially for adults and older children, and are supported by an increasing body of scientific data. The choice of a specific diet will depend on the patient’s age, lifestyle, food preferences, and feeding method. In view of its reduced demands on time for training and supervision, the modified Atkins diet is often the first choice in centers with fewer dietitians.
GLUT1 Deficiency Syndrome and the Ketogenic Dietary Therapies
Authors: Klepper Joerg
Published: March 2022

In 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 < 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

The 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

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 < 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

Overall, 15% of status epilepticus cases admitted to the hospital become super-refractory. In adults, super-refractory status epilepticus has a high mortality rate (> 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

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

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

The 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

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

In 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

The 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

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

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

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

Triheptanoin, 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.
From the First ECMO Patient Into the Future
Authors: Jiritano Federica , Lorusso Roberto
Published: March 2022

Extracorporeal membrane oxygenation (ECMO) is indicated in severe heart or lung failure unresponsive to conventional treatments. In experienced centers, overall survival and survival-to-discharge rates are 70% and 55%, respectively. Since its first application in 1971, several investigations have been able to improve ECMO management and benefits, although complications remain common and life threatening in some cases. Outstanding advancement, in either technology or understanding and management, have been achieved from the very first cases, and substantial changes have been witnessed in ECMO care from the 1970s until now. In the future, most of the current ECMO limits most likely will be overcome. ECMO will be automatically controlled, and the patient will be able to recover at home, with remarkable changes in ECMO patient management and outcome, even at long term.
Development and Staffing of an ECMO Service
Authors: Fowles Jo-anne , Vuylsteke Alain
Published: March 2022

Many centers are developing extracorporeal membrane oxygenation (ECMO) services to meet the need for the increasing number of patients requiring ECMO as a support for cardiac and/or respiratory failure. Developing an ECMO service is a complex process with many interdependent facets. In addition to the infrastructure based around a well-equipped intensive care unit, an ECMO service needs a strong interprofessional team with specific training requirements. Specialized, well-maintained equipment and the ability to transfer patients safely is crucial. This all needs to be underpinned by comprehensive guidelines and robust clinical governance processes. This chapter outlines the principles of developing and staffing an ECMO service. The chapter opens with a stem case outlining the requirements and considerations, followed by some key questions and discussion, concluding with a set of multiple-choice questions.
Echocardiography in the Management of ECMO Patients
Authors: Allen Sara J. , Sidebotham David
Published: March 2022

Echocardiography is an invaluable tool in the management of both veno-arterial (V-A) and veno-venous (V-V) extracorporeal membrane oxygenation (ECMO). Prior to ECMO establishment, echocardiography aids decision-making regarding the appropriate mode of support (V-A or V-V) and provides real-time guidance of guidewire insertion and cannula placement during institution of ECMO. During ECMO support, echocardiography is used to assess the effectiveness of left ventricular (LV) support, to diagnose complications, and to assess readiness to wean from ECMO. In the post-ECMO period, echocardiography is used to assess ongoing cardiac recovery. Consensus guidelines and further studies will enable complications unique to the management of ECMO to be more readily identified.
Airway Management in ECMO Patients
Authors: Howitt Samuel , Maybauer Marc O.
Published: March 2022

Airway management in patients requiring extracorporeal life support (ECLS) in the form of mechanical circulatory support (MCS) or extracorporeal membrane oxygenation (ECMO) can be problematic. In addition to the generic risks of airway management common to all patients undergoing anesthesia, preexisting cardiorespiratory compromise may be exacerbated by induction of anesthesia, leading to rapid and marked deterioration. Consequently, the choice of techniques and drugs to be used requires careful consideration. Recently published guidelines provide a framework for planning and clinical decision-making around the time of anesthetic induction and airway management. Once MCS or ECMO has been established, airway bleeding is relatively common due to a combination of therapeutic anticoagulation, hyperfibrinolysis, and thrombocytopenia often encountered in these patients. Bleeding into the airway may lead to impaired ventilation and inadequate gas exchange requiring emergent procedures to ensure adequate oxygenation.
Ambulance Ground Transportation of ECMO Patients
Authors: van Leeuwen Grace , Di Nardo Matteo , Patroniti Nicolò
Published: March 2022

Extracorporeal membrane oxygenation (ECMO) is generally used in patients with severe respiratory and/or cardiac failure or in patients waiting for solid organ transplantation. ECMO is performed by specialized centers, but patients in need of ECMO are frequently taken care of at other centers. Thus, many ECMO centers have developed transport programs with a mobile unit. Actually, more than 1400 transports on ECMO have been reported. The reported survival of patients transferred with ECMO is equivalent to that reported for patients not transferred with ECMO. This chapter summarizes the story of the ECMO transport, its development and improvement over time and provides suggestions to new centers willing to start this activity. It is imperative, that the staff performing the ECMO transport must be properly trained and experienced not only in ECMO cannulation and management, but also in intensive care transport and air transport medicine.