bluuebunny/crossref_metadata_2025 huggingface dataset:
A 55-Year-Old Male with Right Foot Weakness
Authors: Cohen Jeffrey A. , Mowchun Justin J. , Lawson Victoria H. , Robbins Nathaniel M.
Published: November 2017

Hereditary neuropathies are common. They are often diagnosed when another medical issue begins, for example, orthopedic foot problems or chemotherapy that causes a persistent severe neuropathy. Our patient developed a peroneal neuropathy after a long international airline flight. Initially it was thought to be related to lumbosacral radiculopathy. Careful history, neurological examination, and electrodiagnostic testing was helpful in pointing to a peroneal neuropathy rather than a lumbosacral radiculopathy. Family history in evaluating patients with peripheral neuropathy is essential. The actual examination and testing of relatives may be necessary. Genetic testing for the confirmation of the diagnosis of hereditary neuropathy is outlined. Clinical features of the most common hereditary peripheral are listed. It is important to recognize that a patient has a hereditary neuropathy before therapy with a chemotherapeutic agent is initiated.
A 28-Year-Old Male with Weakness in the Setting of Cancer
Authors: Cohen Jeffrey A. , Mowchun Justin J. , Lawson Victoria H. , Robbins Nathaniel M.
Published: November 2017

Chemotherapy-induced peripheral neuropathy is a common complication of cancer therapy. The diagnosis is generally straightforward, based on the temporal association of symptoms with the offending agent. However, it can sometimes take on a different form of severe, fulminant neuropathy and must be differentiated from other neurologic conditions that occur in the setting of cancer. Particular care must be taken in the patient with clinical indicators of longstanding, hereditary neuropathy as these can confer a distinctive susceptibility to neurotoxicity. The diagnosis relies on an index of suspicion and the exclusion of mimics of toxic neuropathy. The most important and common agents responsible for toxic neuropathy and their range of effects on nerve are discussed.
Improving Symptoms
Authors: Chong Ji Y. , Lerario Michael P.
Published: November 2017

Patients with minor stroke symptoms or rapid improvement of symptoms are at high risk of subsequent worsening. Acute treatment with IV tPA is warranted if there is still a residual deficit that is disabling. Waiting for resolution of symptoms removes the possibility of some acute treatments that can only be administered within narrow time windows.
Hypertension and Confusion
Authors: Chong Ji Y. , Lerario Michael P.
Published: November 2017

Posterior reversible encephalopathy syndrome is a clinical–radiographic syndrome of progressive headaches, blurred vision, confusion, and seizures in the setting of vasogenic edema on brain imaging, which is often localized to the posterior white matter. The symptoms are classically triggered by severe hypertension, pregnancy and the puerperium, or exposure to immunosuppressive medications. The symptoms can be reversible if the offending etiology is quickly removed, but permanent deficits can remain if strokes or hemorrhage complicate the clinical course.
Worst Headache of Her Life
Authors: Chong Ji Y. , Lerario Michael P.
Published: November 2017

Aneurysmal subarachnoid hemorrhage typically causes sudden severe headache. Diagnosis is made by CT scan in most cases, but lumbar puncture may be needed if CT findings are normal and suspicion is high. Rapid evaluation and treatment are important because of the high morbidity and mortality associated with rebleeding and vasospasm.
Insights into the Human Brain
Authors: Hari Riitta , Puce Aina
Published: November 2017

The aim of MEG and EEG recordings is to obtain new information about human brain function, especially with respect to the millisecond-range neurodynamics in both the healthy and diseased brains and to relate this information to observed behavior. This chapter reviews some basic principles of human brain structure and function, including thalamocortical and other kinds of intrabrain connectivity that may be relevant for the design and interpretation of MEG and EEG recordings. Some basic aspects of electrical signaling in neurons and neural populations of the cerebral cortex are presented, including membrane potentials, action potentials, and postsynaptic potentials. The contribution of these electrical signals to MEG and EEG records are examined.
An Overview of EEG and MEG
Authors: Hari Riitta , Puce Aina
Published: November 2017

This chapter discusses the rather different histories of MEG and EEG. EEG has been used as a tool of clinical diagnostics since the 1930s with visual inspection of spontaneous EEG activity in patients suffering from various brain disorders, particularly epilepsy. For MEG, the evolution of applications has been the opposite: the first recordings were made in research laboratories and the recordings started by averaging a very high number of single trials, and it took some time before low-noise MEG equipment became available to allow single-trial analyses. Only with recent technical developments, especially with the advent of whole scalp–covering devices, has MEG become increasingly popular in the clinical environment. We discuss the evolution of both techniques with respect to the measurement of brain rhythms and evoked and event-related responses.
Practicalities of Data Collection
Authors: Hari Riitta , Puce Aina
Published: November 2017

This chapter provides a number of suggestions about optimization of MEG/EEG recording sessions to guarantee as good signal quality and as high signal-to-noise ratio as possible. It also advices for performing replicability checks on the data. The practical aspects of preparing and performing an EEG recording (skin preparation, electrode-impedance measurement) and postrecording infection control are presented. Similarly, practicalities of performing MEG recordings are discussed. Measurement of MEG sensor-array location with respect to landmarks on the scalp and different methods for the measurement of EEG electrode positions are presented. The chapter ends with a discussion on electrical safety in the MEG/EEG laboratory.
Data Acquisition and Preprocessing
Authors: Hari Riitta , Puce Aina
Published: November 2017

This chapter introduces principles of MEG/EEG data acquisition and preprocessing. MEG and EEG are recorded as analog (continuous-value) signals, amplified, and then filtered to remove undesirable components with lower and higher frequencies relative to the signals of interest. The analog signals are transformed to digital form by sampling (also called digitization) at rates that avoid aliasing, a very serious signal distortion described in this chapter; the appropriate sampling frequencies are at least 2 times the highest frequency in the sampled data (so-called Nyquist criterion). Different filter types (lowpass, highpass, bandpass, and notch) and their cut-off frequencies and roll-offs are examined. Examples of pitfalls that can occur with incorrectly selected filters and sampling rates are presented.
Artifacts
Authors: Hari Riitta , Puce Aina
Published: November 2017

This chapter focuses on different types of biological and nonbiological artifacts in MEG and EEG recordings, and discusses methods for their recognition and removal. Examples are given of various physiological artifacts, including eye movements, eyeblinks, saccades, muscle, and cardiac activity. Nonbiological artifacts, such as power-line noise, are also demonstrated. Some examples are given to illustrate how these unwanted signals can be identified and removed from MEG and EEG signals with methods such as independent component analysis (as applied to EEG data) and temporal signal-space separation (applied to MEG data). However, prevention of artifacts is always preferable to removing or compensating for them post hoc during data analysis. The chapter concludes with a discussion of how to ensure that signals are emanating from the brain and not from other sources.
Brain Rhythms
Authors: Hari Riitta , Puce Aina
Published: November 2017

This chapter provides examples of studies of MEG and EEG brain rhythms that have considerably increased understanding of the human brain’s sensory, motor, cognitive, and affective functions. Parieto-occipital alpha, Rolandic mu and auditory-cortex tau rhythms, as well as more widely spread beta, theta, gamma, delta and ultra-slow oscillations are described. Additionally, MEG/EEG signal changes that accompany different vigilance states, such as drowsiness and sleep, as well as anesthesia, are discussed. We emphasize the importance of timing information that MEG and EEG recordings, including the brain rhythms, provide. In this and subsequent chapters, we rely somewhat on our own studies and experiences, so as to give educational insights from the pitfalls and challenges we ourselves have experienced.
Other Sensory Responses and Multisensory Interactions
Authors: Hari Riitta , Puce Aina
Published: November 2017

This chapter discusses olfactory and visceral responses as well as the MEG/EEG signature of multisensory interaction. Olfactory stimuli can be embedded in a continuous humified airflow where the stimuli are presented at intervals of tens of seconds to avoid short-term habituation. Visceral stimulation typically requires purpose-built stimulating electrodes for direct access to the viscera. Studies of multisensory interaction are necessary because our everyday experiences involve inputs from multiple senses, the temporal coincidence of which allows the brain to construct representations of unique objects or events. Detection and correct interpretation of the nonlinear multisensory interactions call for careful considerations of both the sites of interaction and the changes in the amplitudes of evoked responses and spontaneous activity.
Motor Function
Authors: Hari Riitta , Puce Aina
Published: November 2017

Voluntary movements are preceded by slow brain activity, visible in EEG as the Bereitschaftspotential (the readiness potential), and in MEG as the readiness field. These slow shifts can begin a few seconds before movement onset in the primary motor cortex and in the premotor areas. Cortex–muscle coherence refers to coupling between MEG/EEG signals and the surface EMG of a steadily contracted muscle; it typically occurs at around 20 Hz and implies an efferent drive from the cortex to the muscle. Corticokinematic coherence can be measured as the coupling between MEG/EEG signals and the acceleration or velocity of a rhythmically moving limb; it typically occurs are the movement frequency and its first harmonic. Coherence of MEG/EEG signals can be computed also with respect to other peripheral signals, such as the fundamental frequency of the voice measured with an accerometer above the subject’s throat.
Brain Signals Related to Change Detection
Authors: Hari Riitta , Puce Aina
Published: November 2017

This chapter discusses, in the context of the predictive-coding framework, evoked responses to various changes in the environment and describes how the responses are related to variations in stimulus probability and the subject’s expectations. The focus is on three well-known responses: (a) the mismatch negativity peaking at 100 to 250 ms and elicited to changes in stimulus attributes, even when the stimuli are not attended to, (b) the P300 response peaking about 300 ms after attended low-probability “oddball” stimuli, and (c) the N400 peaking about 400 ms after semantic or lexical violations of sentences presented either visually or auditorily. Continent negative variation and error-related negativity are introduced as well.
Brain Disorders
Authors: Hari Riitta , Puce Aina
Published: November 2017

This chapter discusses clinical applications of spontaneous EEG and MEG as well as evoked responses in epileptic and stroke patients, and in presurgical mapping (including identification of the central sulcus). EEG and MEG remain, due to their excellent temporal resolution, the methods par excellence for diagnosing and identifying epileptic syndromes. Timing of discharges can differentiate primary and secondary (mirror) epileptic foci. In contrast to studies of clinical populations for research purposes, clinical assessment is always based on findings in individual subjects, and the tests thus have to be reliable with high specificity and high sensitivity, showing statistically significant differences compared with normative values of healthy subjects with similar attributes, including age. The chapter ends by discussing EEG monitoring in coma or brain death.
MEG/EEG in the Study of Brain Function
Authors: Hari Riitta , Puce Aina
Published: November 2017

This chapter summarizes some relative advantages and disadvantages of MEG and EEG, most of which have been previously elaborated. MEG and EEG are the two sides of the same coin and provide complementary information about the human brain’s neurodynamics. The combined use of MEG or EEG together and with other noninvasive methods used to study human brain function is advocated to be important for future research in systems and cognitive/social neuroscience. This chapter also examines combined use and interpretation of MEG/EEG with MRI/fMRI, and performing EEG recordings during non-invasive brain stimulation.
Overview: Ketogenic Diets and Pediatric Epilepsy
Authors: Kossoff Eric H.
Published: November 2017

When the classic ketogenic diet was created in 1921, it was one of the few treatments in existence for the treatment of epilepsy. As a result, its use was widespread and publications were plentiful. The advent of modern anticonvulsant drugs led to relative disuse of the ketogenic diet for many decades, however, until the Charlie Foundation reinvigorated interest and research in 1994. Today there are four major diets available, myriad methods to start and manage patients receiving this therapy, and growing numbers of adolescents and adults being treated. This section, “Ketogenic Diet for Epilepsy in the Clinic,” discusses all of these advances in practical implementation of dietary therapy. In addition, chapters focus on the “indications” for dietary therapy that are both proven and investigational at this time. Lastly, methods to prevent side effects are outlined.
“Alternative” Ketogenic Diets
Authors: Neal Elizabeth
Published: November 2017

As the classical ketogenic diet fast approaches a centennial anniversary, the wider ketogenic landscape has expanded considerably both in application and implementation. Although still extensively used today, this traditional dietary therapy has been the basis for development of alternative ketogenic protocols. One ketogenic diet incorporating medium chain fatty acids is used for many children and adolescents, who benefit from the generous carbohydrate allowance facilitated by the increased ketogenic potential of medium chain triglycerides. More recently, two less restrictive dietary approaches have been developed: the low glycemic index treatment and the modified Atkins diet. These are now being used worldwide as the advantages of a more liberal ketogenic diet are recognized, especially in adults and older children, supported by an increasing body of scientific data. This chapter explores the background and evidence for use of these alternative ketogenic diets.
Ketogenic Diet for Other Epilepsies
Authors: Hsieh David T. , Thiele Elizabeth A.
Published: November 2017

The ketogenic diet is the treatment of choice for epilepsy in certain disorders of brain metabolism, in particular glucose transporter protein 1 deficiency and pyruvate dehydrogenase deficiency. The International Ketogenic Diet Study Group has listed several other conditions for which the ketogenic diet has been reported as being particularly beneficial and could be offered earlier. Whether efficacy in these conditions is due in part to the broad-spectrum efficacy of the ketogenic diet or to specific mechanisms specific to these conditions is still under investigation. This chapter discusses the use of dietary therapies for the treatment of epilepsy in certain genetic disorders, including Rett syndrome and tuberous sclerosis complex, as listed by the International Ketogenic Diet Study Group, and additionally discusses the use of epilepsy dietary therapies in patients with Angelman syndrome and Sturge-Weber syndrome.
Preventing Side Effects and Diet Discontinuation
Authors: Herren Cherie L. , Said Rana R.
Published: November 2017

Generally, the ketogenic diet is well tolerated. On average, sixty percent of patients remain on the diet for over six months; those who stop typically do so due to lack of efficacy rather than tolerability. 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. With appropriate monitoring and supplementation, these adverse effects can be minimized so the patient can remain on the diet as long as indicated. In addition, there may be social issues, including refusal to eat and managing special occasions and holidays. With support and resources, most families are able to overcome these obstacles. Weaning from dietary therapy must be done gradually and with close supervision, as there may be an increase in seizures. Patients must be provided support and direction on how to safely discontinue the diet.
Glucose and Ketone Metabolism in the Aging Brain
Authors: Cunnane Stephen C. , Courchesne-Loyer Alexandre , St-Pierre Valerie , Vandenberghe Camille , Croteau Etienne , Castellano Christian-Alexandre
Published: November 2017

Brain glucose uptake is impaired in Alzheimer’s disease (AD). A key question is whether cognitive decline could be delayed if this defect were at least partly corrected or bypassed. Ketones (or ketone bodies) such as beta-hydroxybutyrate and acetoacetate are the brain’s main alternative fuels. Several studies have shown that in mild-to-moderate AD, brain ketone uptake is similar to that of healthy age-matched controls. Published clinical trials show that increasing ketone availability to the brain via nutritional ketosis has modest benefits on cognitive outcomes in mild-to-moderate AD and in mild cognitive impairment. Nutritional ketosis can be safely achieved by a high-fat ketogenic diet or supplements providing medium chain triglycerides. Given the acute dependence of the brain on its energy supply and the ineffectiveness of current therapeutic strategies for AD consideration be given to correcting the underlying problem of deteriorating brain fuel supply during aging.
Ketogenic Diet and Ketones for the Treatment of Traumatic Brain and Spinal Cord Injury
Authors: Streijger Femke , Plunet Ward T. , Tetzlaff Wolfram
Published: November 2017

Ketogenic diets (KD)—high in fat, adequate in protein, and very low in carbohydrates—were developed almost a century ago and are still used clinically for drug-resistant epilepsy and some rare metabolic disorders. Possible new indications for cancers, diabetes, obesity, and neurodegenerative disorders are being trialed in humans based on a growing body of preclinical data showing efficacy. However the underlying mechanisms of KD remain incompletely understood. This chapter focuses on the neuroprotective effects of KD after spinal cord injury (SCI) and traumatic brain injury (TBI), and discusses possible mechanisms of action. It considers the possible role of ketone bodies as alternative fuels for mitochondrial energy utilization and the actions of ketones outside the mitochondria as agonists of antioxidant and anti-inflammatory pathways. It places these into context with the known pathophysiology of SCI and TBI, and discusses possible roles of KD and ketone bodies for their treatment.
Anti-Inflammatory Effects of a Ketogenic Diet
Authors: Dupuis Nina , Auvin Stéphane
Published: November 2017

The high-fat, low-carbohydrate ketogenic diet (KD) is an established and proven treatment for pharmacoresistant epilepsy. Recently, the KD is being explored for some inflammation-induced epileptic encephalopathies. Given the broad neuroprotective properties of the KD in various experimental models of neurological disorders, there are yet additional potential future uses. Consistent with this, there is growing evidence that the KD exerts anti-inflammatory activity. Ketone bodies, caloric restriction, and polyunsaturated fatty acids 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.
Overview of Ketogenic Diet in the Laboratory
Authors: Boison Detlev
Published: November 2017

Increased clinical interest in the ketogenic diet and similar metabolic treatments has naturally spurred research into mechanisms underlying their anticonvulsant/antiepileptogenic efficacy; significant progress and new insights are being made after many decades of relative obscurity. This section, “Ketogenic Diet in the Laboratory,” includes discussions of a number of molecular targets that are affected by ketogenic diet feeding. New insights into mechanisms, combined with clinical observations, are potentially expanding the utilitiy of this metabolic approach. In parallel, several alternative experimental methods to either elucidate or mobilize ketogenic diet mechanisms are explored. Based on this laboratory research, putative and novel uses for metabolic treatments are proposed.
Ketogenic Diet and PPARgamma
Authors: Simeone Timothy A.
Published: November 2017

The ketogenic diet (KD) is an effective therapy for many patients with refractory epilepsy. It engages a wide array of antioxidant and anti-inflammatory processes and improves mitochondrial function, which is thought to underlie its neuroprotective, antiseizure, and disease-modifying effects. Potential roles of ketone bodies in these mechanisms are discussed elsewhere in this volume. This chapter focuses on the role of KD fatty acids as potential ligands for the nutritionally regulated nuclear transcription factor peroxisome proliferator activated receptor gamma (PPARgamma). PPARgamma regulates many of the pathways identified in the mechanism of the KD and, in recent years, has become a potential therapeutic target for neurodegenerative diseases. This chapter reviews what is known concerning PPARgamma in the brain, the evidence that PPARgamma has neuroprotective and antiseizure properties, and the evidence suggesting that PPARgamma may be involved in the antiseizure mechanisms of the ketogenic diet.
Metabolic Therapy and Pain
Authors: Ruskin David N.
Published: November 2017

Chronic pain is associated strongly with poor quality of life. Drug treatments for pain can be problematic; with the understanding that chronic pain syndromes often involve derangement of homeostasis, there is an increased interest in applying nonpharmacological metabolic therapies. This chapter surveys clinical and animal research into the effects of fasting, calorie restriction, ketogenic diet, and polyunsaturated fatty acid supplementation on pain. These dietary treatments can significantly ameliorate pain in inflammatory and neuropathic disorders. The choice among these treatments might depend on the specific pain syndrome and the tolerance of the patient for particular dietary modifications. Several possible mechanisms are discussed, some of which might be in common among these treatments, and some treatments might engage multiple mechanisms. Multiple mechanisms acting together could be ideal for restoring the disordered metabolism underlying some pain syndromes.
Ketogenic Diet, Aging, and Neurodegeneration
Authors: Xu Kui , LaManna Joseph C. , Puchowicz Michelle A.
Published: November 2017

The brain 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. Research has shown that ketosis is neuroprotective against ischemic insults in rodents. This review focuses on investigating the mechanistic links to neuroprotection by ketosis in the aged. Recovery from stroke and other pathophysiological conditions in the aged is challenging. Cerebral metabolic rate for glucose, cerebral blood flow, and 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 hypoxic inducible factor-1alpha (HIF1α) and its downstream effects on intermediary metabolism. The chapter hypothesizes that ketone bodies play a role in the restoration of energy balance (stabilization of ATP supply) and act as signaling molecules through the up-regulation of salvation pathways targeted by HIF1α.
Endocrine and Reproductive Effects of Ketogenic Diets
Authors: Harney Jacob P. , Gudsnuk Kathryn , Patel Ami , Vellipuram Anantha R. , Bandaru Sathyajit , Butler David
Published: November 2017

This chapter reviews endocrine, behavioral, and reproductive outcomes of the ketogenic diet (KD) in rodent mouse and rat models. KD treatment can result in conditions seen in metabolic syndrome, including dyslipidemia and inflammation. Females raised on low protein KDs will experience delayed puberty onset. Results presented suggest an increase in ketones and a decrease in spatial memory as percent protein drops. Postpubertal female pups fed KD experienced similar cognitive decline to KD-fed dams, despite consuming only normal rodent chow since weaning. This finding is consistent with the development of anatomical differences in the brains of pups from KD-fed versus rodent chow–fed controls. A thorough evaluation of the effects of different lipid and protein profiles (amount and type) will be necessary if KDs are going to be safe and effective long-term therapies for both sexes and in neurological disorders besides pediatric intractable epilepsy.
Metabolic Seizure Resistance via BAD and KATP Channels
Authors: Martínez-François Juan Ramón , Danial Nika N. , Yellen Gary
Published: November 2017

On a ketogenic diet, ketone bodies provide an alternative fuel, replacing much of the glucose used ordinarily by the brain. This switch is thought to underlie its anticonvulsant effects. 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 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 decreased glucose metabolism exhibit a marked increase in the activity of neuronal ATP-sensitive potassium (KATP) channels and strong resistance to behavioral and electrographic seizures in vivo. This seizure resistance is lost upon genetic ablation of KATP channels, suggesting that KATP channels mediate BAD’s anticonvulsant effect.
Lactate Dehydrogenase
Authors: Sada Nagisa , Inoue Tsuyoshi
Published: November 2017

Glucose is transported into neurons and used as an energy source. It is also transported into astrocytes, a type of glial cell, and converted to lactate, which is then released to neurons and used as another energy source. The latter is called the astrocyte-neuron lactate shuttle. Although the lactate shuttle is a metabolic pathway, it also plays important roles in neuronal activities and brain functions. We recently reported that this metabolic pathway is involved in the antiepileptic effects of the ketogenic diet. Lactate dehydrogenase (LDH) is a metabolic enzyme that mediates the lactate shuttle, and its inhibition hyperpolarizes neurons and suppresses seizures. This enzyme is also a molecular target of stiripentol, a clinically used antiepileptic drug for Dravet syndrome. This review provides an overview of electrical regulation by the astrocyte-neuron lactate shuttle, and then introduces LDH as a metabolic target against epilepsy.
Overview of Ketone-Based Metabolism
Authors: D’Agostino Dominic P.
Published: November 2017

Nutritional ketosis produces a nonpathological hyperketonemia resulting from decreased glucose availability, lower insulin, and increased fat oxidation. However, the restrictive nature of the ketogenic diet (KD) has limited the clinical applicability of therapeutic ketosis, due to practical considerations. Emerging data suggests that many of the benefits of the KD are mechanistically attributable to the ketone bodies or specific medium chain triglycerides, and this has motivated investigators to develop strategies to further augment the efficacy of the KD or use metabolic-based supplements to circumvent the need for dietary restriction to improve compliance and the maintenance of this therapeutic state. This section, “Ketone-Based Metabolism: General Health and Metabolic Alternatives,” includes chapters that discuss the expanding medical and performance applications of nutritional ketosis and the emerging science of ketones and other related metabolites as alternative fuels and potent signaling molecules.
Identifying the Molecular Mechanism of the Medium Chain Triglyceride (Ketogenic) Diet
Authors: Walker Matthew C. , Williams Robin S.B.
Published: November 2017

The medium chain triglyceride (MCT) ketogenic diet provides a highly effective and commonly used approach for treating drug-resistant epilepsy. It is associated with elevated levels of two MCT-derived fatty acids, decanoioc and octanoic acids. Researchers have identified a role for decanoic acid and a range of novel related chemicals in seizure control in multiple acute in vitro and in vivo models. A principal mechanism of decanoic acid is direct inhibition of AMPA receptors, key excitatory neurotransmitter receptors widely recognized as a target for seizure control. These data suggest a therapeutic mechanism of the MCT ketogenic diet through a direct fatty acid–dependent mechanism, independent of ketosis. This discovery will enable the development of an improved and, potentially, better-tolerated diet and the generation of a corresponding pharmaceutical approach. The diet should be termed the MCT diet, as the consequent ketosis may not be necessary for seizure control.
Triheptanoin in Epilepsy and Beyond
Authors: Borges Karin
Published: November 2017

Triheptanoin, the triglyceride of heptanoate (C7 fatty acid), is a novel treatment that is being used to treat patients with rare genetic metabolic disorders. When taken orally, triheptanoin is hydrolyzed in the gastrointestinal tract to heptanoate, which is thought to diffuse into the blood and body. Heptanoate and its liver ketone metabolites are then metabolized within cells to propionyl-CoA, which after carboxylation produces succinyl-CoA, resulting in anaplerosis—the refilling of a deficient tricarboxylic acid cycle. Here, data are summarized and discussed in relation to triheptanoin’s anticonvulsant effects in rodent seizure models. Biochemical data reveal that metabolic alterations found in brains of rodent seizure models can be restored by triheptanoin. Moreover, there are increasing preclinical and clinical studies indicating that triheptanoin is beneficial in other neurological and neuromuscular disorders, which are summarized here. Thus, triheptanoin seems to be a promising treatment for a variety of clinical conditions.
Politzer’s Otology Clinic and the Discovery of the Caloric Test
Authors: Baloh Robert W.
Published: November 2017

Robert Bárány began his training in Adam Politzer’s Otology Clinic at the University of Vienna in October 1903 after completing his surgical training at the Vienna General Hospital. During his training, Bárány became friends with Gustav Alexander, who already had been offered a position in Politzer’s clinic. Alexander stimulated Bárány’s interest in the vestibular apparatus of the inner ear and was influential in helping Bárány obtain his appointment in Politzer’s clinic. It was well known in Politzer’s clinic that one had to be extremely careful regarding the temperature of the water used to irrigate the ear canals in removing cerumen, otherwise the patient would become dizzy. Bárány discovered the mechanism of this caloric reaction and eventually received the Nobel Prize in Medicine. Bárány’s findings were considered to be pivotal in clinical otology. His colleagues at the clinic were less magnanimous in their praise of Bárány’s accomplishments and questioned his integrity.
Hallpike and the Pathology of Ménière’s Disease
Authors: Baloh Robert W.
Published: November 2017

Joseph Toynbee, an English physician, believed that the only way to develop a rational strategy for the treatment of ear diseases was to dissect the temporal bones of patients with known inner ear diseases. In his book Diseases of the Ear (1860), Toynbee noted that not one dissection of a diseased ear had been done before 1800, although thousands of dissections had been done on most other organs of the body. The techniques for examination of the temporal bones developed by Joseph Toynbee had multiple technical problems. German otolaryngologist Karl Wittmaack solved these problems and revolutionized the study of temporal bone specimens. An otologist in London, Charles Skinner Hallpike, became interested in studying temporal bone pathology while visiting Wittmaack’s clinic in Germany. Hallpike went on to develop his own temporal bone laboratory in which he worked with neurosurgeon Hugh Cairns to describe the pathology of Ménière’s disease.
Semont and Epley Maneuvers
Authors: Baloh Robert W.
Published: November 2017

Until 1980, treatment of benign paroxysmal positional vertigo (BPPV) mainly consisted of reassuring patients of the benign nature of the condition and a recommendation that they avoid the critical position changes that induced the vertigo. Most patients had a spontaneous remission, although not infrequently the condition recurred. The same benign course was seen whether BPPV occurred after head trauma or an ear infection or if it occurred spontaneously. Although brain lesions could produce positional vertigo and nystagmus, the stereotyped torsional vertical nystagmus of BPPV was a reliable signature of a benign inner ear disorder. In the 1980s, Alan Semont, a physical therapist in Paris, and John Epley, an otolaryngologist in Oregon, proposed the first treatment maneuvers specifically designed to remove otoconial debris from the posterior semicircular canal and cupula. Although initially there was skepticism regarding the efficacy of these maneuvers, they have been proven effective in multiple controlled treatment trials.
“Are My Children at Risk, Doctor?”
Authors: Walsh Richard A.
Published: November 2017

Few patients with Parkinson’s disease will be found to have a monogenic cause of their disease, even among those with early onset symptoms. The identification of a genetic etiology will in general have no implications on management but can be helpful in offering a prediction on prognosis, predicting response to treatment, and allowing genetic counseling to take place. Insights into the molecular mechanisms provided by a greater understanding of the genetics of Parkinson’s disease may offer the best hope for identifying future disease-modifying therapies. Next-generation sequencing techniques offer a more cost-effective approach to pursuing genetic testing where indicated.
“My Arm Is Not Working”
Authors: de Bie Robertus M. A. , Ten Holter Susanne E. M.
Published: November 2017

Corticobasal syndrome is a clinical diagnosis based on the presence of one or more movement disorders suggestive of basal ganglia dysfunction, typically asymmetrical, with evidence of associated cortical dysfunction. This is a pathologically heterogeneous group of disorders that can share a common phenotype. Corticobasal degeneration is one of these pathologies, representing one of the rarest forms of atypical parkinsonism. When confronted with a patient with higher cortical dysfunction, specific assessment for apraxia, cortical sensory loss, and cognition is indicated. Corticobasal syndrome is currently untreatable, regardless of the nature of the underlying pathology, and in most cases progression is fast with significant disability that is typically unresponsive to levodopa.
“I See Them Sitting on My Bed, Doctor”
Authors: Fox Susan H. , Picillo Marina
Published: November 2017

Many movement disorders specialists would consider dementia with Lewy bodies to be on one end of a spectrum of presentations associated with Lewy body pathology. Parkinson’s disease with preserved cognition sits at the other end of the spectrum, and over time it can be associated with a greater cortical Lewy body burden and related cognitive impairment. It is unclear what determines to what degree cognitive impairment is involved in a given patient, and the arbitrary time-based division between Parkinson’s disease and dementia with Lewy bodies is imperfect, although it serves to help recognition of this group of patients in whom management needs to be appropriately tailored.
Siblings with Instability
Authors: Walsh Richard A.
Published: November 2017

Over the past 5 years, there has been a shift in the approach to searching for a genetic diagnosis in familial ataxic syndromes. Whereas in the past, a limited but expensive search through a selection of commercially available genes using Sanger sequencing was performed, there is now widespread availability of gene panels utilizing next-generation sequencing techniques. This is an efficient and powerful approach that may achieve a diagnosis in more than 30% of patients with a familial ataxia that remain undiagnosed. However, accurate phenotyping remains critical to allow interpretation of sequence variants of uncertain significance, to identify biomarkers that may be useful to monitor future therapies, and to assist with the identification of underlying pathophysiology.
Advanced Treatment for Dystonia
Authors: de Bie Robertus M. A. , Ten Holter Susanne E. M.
Published: November 2017

Deep-brain stimulation is a last resort for the management of dystonia or dystonic movement disorders when oral or injectable therapies do not provide adequate relief to allow an acceptable quality of life. The underlying pathogenesis of dystonia is less well understood than in Parkinson’s disease, in which deep-brain stimulation is generally expected to provide effective and long-lasting benefit. Furthermore, it is likely that dystonia represents a number of different basal ganglia pathologies. The response of dystonia to deep-brain stimulation is typically delayed for up to weeks or months following a change in stimulation parameters. All of these factors make it more difficult to predict outcomes in dystonia following deep-brain stimulation, thus making patient selection all the more important.
The Ebbing Tide
Authors: Aminoff Michael J.
Published: November 2017

Charles Bell spent his final days in the chair of surgery at the University of Edinburgh. He was not well off and was disappointed that his reputation did not bring more referrals and requests for consultation. Despite his good intentions, however, he could not get back fully into an academic way of life. He had lost his sense of urgency and purpose, and he preferred to spend much time fishing and painting. He developed angina pectoris and, on 29 April 1842, died suddenly of a heart attack in the arms of his wife at Hallow Park, near Worcester, while on his way to London. He died a poor man, having been more concerned with teaching, writing, and advancing knowledge than with the acquisition of wealth, and his wife was therefore granted a civil pension by a grateful government.
The ABNS Oral Board Examination
Authors: Couldwell William T.
Published: November 2017

This chapter describes the American Board of Neurological Surgery (ABNS) Oral Board Examination and the specific requirements of candidate selection and eligibility for taking the examination. The actual organization of the examination, including how examiners score each candidate and the rigorousness of the process, are described. Methods of grading, discussion of marginal candidates, pass/fail determination, and outcomes are covered. The ABNS Oral Board Examination is the final step in the certification process of an individual neurosurgeon by the Board. It is usually undertaken within 5 years of completion of residency or postgraduate fellowship training. Its purpose is to explore the knowledge base of candidates, including how candidates apply their knowledge to provide safe and rational care of patients.
Vascular Neurosurgery
Authors: Leipzig Thomas
Published: November 2017

Vascular neurosurgery has long been one of the focal points of neurosurgical practice, and the topic is routinely included in the Oral Board Examination process. Each case involves clinical and diagnostic acumen, a solid grasp of the natural history and treatment risks, consideration of operative approaches, alternative treatment options, and the management of potentially catastrophic complications, as a result of what we have done or what we failed to do. Five cases are discussed in this chapter, and for each case the history and physical symptoms, imaging studies, analyses of the cases and treatment plans, and complications are provided. Key points are also presented after each case. The cases discussed include an aneurysmal subarachnoid hemorrhage (aSAH), an unruptured brain arteriovenous malformation (AVM), an intracerebral hemorrhage (ICH), a spinal dural arteriovenous fistula (dAVF), and symptomatic carotid stenosis.
Pain
Authors: Slavin Konstantin V.
Published: November 2017

Historically, surgery for pain has been a large part of general neurosurgical practice. A variety of destructive and decompressive interventions have been developed over the years, and a number of comprehensive textbooks have summarized neurosurgical involvement with management of all kinds of medically refractory pain syndromes. It is included in the core neurosurgical education curriculum and is an integral part of neurosurgical knowledge that is tested during the Oral Board Examination. Not surprisingly, cases involving complex pain conditions that require neurosurgical interventions routinely show up during examinations, and it is expected that examinees are comfortable performing these interventions and able to discuss indications, surgical details, outcomes, and complications. Cases include trigeminal neuralgia, plexopathy, cordotomy versus morphine pain pump for cancer pain, dorsal root entry zone myelotomy for brachial plexus avulsion, and complex regional pain syndrome.
Epilepsy and Functional Neurosurgery
Authors: Tandon Nitin , Slavin Konstantin V.
Published: November 2017

This chapter covers several aspects of the management of seizures and epilepsy relevant to a general neurosurgical practice. First, all candidates should know how to manage a patient presenting with a new-onset seizure or in status epilepticus with a brain lesion or after a craniotomy. Second, they are expected to be able to explain how to perform fundamental epilepsy procedures such as a temporal lobectomy for hippocampal sclerosis or resection of an epileptogenic lesion. Third, it is useful to have a clear process in place for mapping language and motor function for the resection of tumors located in the eloquent cortex. Lastly, the thought process behind developing an appropriate plan for the surgical management of movement disorders and the technical nuances of managing such cases are discussed.
Neurology
Authors: O’Phelan Kristine
Published: November 2017

The purpose of the Oral Board Examination is to determine a candidate’s competency in neurosurgical disorders, but also neurological disorders, which may mimic neurosurgical conditions. It is not uncommon for a candidate to be presented imaging studies that clearly appear surgical; however, after carefully listening to the history and relevant neurological findings, it will become apparent that the imaging does not explain the patient’s symptoms. Some of the common neurological ailments that the Oral Board examinee needs to be well aware of include amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Guillain-Barré syndrome, and Parsonage=Turner syndrome (brachial plexitis), some of which are covered either in this chapter or in other relevant chapters.
Research
Authors: Hellman Samuel
Published: November 2017

Research is an integral part of the author’s academic life. His clinical research began with how best to combine surgery, radiation, and chemotherapy to increase tumor cure. Since these modalities had different mechanisms of action as well as different toxicities and limitations, combining them offered the potential of more effective and less morbid treatments. While he began these studies with Hodgkin and other lymphomas, breast cancer was a major emphasis throughout his career. Lymphoma treatment has improved greatly, resulting in marked increases in cure rates. Breast cancer treatment now is more efficacious, with a significant reduction in the extent of surgery and its resulting functional and aesthetic effects. The author was an active participant in these efforts internationally. With Ralph Weichselbaum’s group he has shown how metastases can be cured early in their evolution.
Heroes
Authors: Hellman Samuel
Published: November 2017

The author’s medical heroes are recognized not only for their scientific accomplishments but also for their public actions to benefit humankind in general. Thomas Hodgkin is famous for the eponymous disease named for him and Marie Curie for the discovery of the first known radioactive substances, polonium and radium. But both did much more: Hodgkin, in his efforts to improve public health in Great Britain and in the Levant; and Curie, in harnessing diagnostic X-ray mobile field units in World War I, as well as making radium available for cancer treatment by publicizing its effectiveness and raising funds for its purchase and use at major international cancer centers. It is this continuum of involvement from science to public benefit that makes them the author’s heroes.
Friendly Fire
Authors: Webster Lynn R.
Published: November 2017

“Friendly Fire” tells the story of Jason Bing, a soldier who became dependent on pain medications prescribed for a service-related injury and who faced the stigma placed upon pain treatment and addiction within the U.S. military. His story illustrates the way that nearly all people in pain have to deal with prejudice and ignorance surrounding pain and opioids, regardless of what part of society they belong to. Chapter key idea: Cultural attitudes toward pain too often make a pain experience worse than it has to be.
The New Scarlet Letter
Authors: Webster Lynn R.
Published: November 2017

“The New Scarlet Letter” tells about Hal Garner, a former NFL player whose life fell apart after he experienced a career-ending injury and began abusing his opioid pain medications. Branded with the “new scarlet letter” A for addiction, he went through estrangement from friends and family, the loss of income and property, embarrassing public exposure, arrest, and multiple stints behind bars. Finally, though, a combination of standard and innovative treatments helped him come off opioids and begin rebuilding his life. Chapter key idea: Opioids can become more curse than cure, but it’s possible to overcome addiction to these medications.
Soul Mates
Authors: Webster Lynn R.
Published: November 2017

“Soul Mates” introduces readers to John Kay and Marsha Miller, two residents of the same small town in Utah. John developed chronic pain through two separate accidents on the job, and Marsha injured her back in a simple office mishap. Both saw their marriages and some of their other personal relationships fall apart after developing pain. But then one day they met in Dr. Webster’s office-and the friendship that resulted eventually ripened into love. As a married couple, they understood and helped each other through the ups and downs of their pain experiences. Chapter key idea: You may need only one person in your life to experience the joy of living again.