bluuebunny/crossref_metadata_2025 huggingface dataset:
A 20-year-Old Male with Acute Lower-Extremity Weakness
Authors: Cohen Jeffrey A. , Mowchun Justin J. , Lawson Victoria H. , Robbins Nathaniel M.
Published: November 2017

A metabolic myopathy may be an overlooked etiology of recurrent exercised-induced weakness. This chapter discusses the clinical features and diagnostic considerations for adult patients with suspected metabolic myopathy. Adult patients with carbohydrate or fatty acid disorders typically have a history since childhood of exercise-induced myalgias, cramps, and fatigue. Episodes of myoglobinuria tend to present later, usually in the second decade. For any unexplained myopathy, especially if there is concern for a metabolic myopathy, there should also be consideration of a mitochondrial disease. Many mitochondrial disorders present with multiple neurological problems, such as deafness, seizures, encephalopathy, ptosis, or ophthalmoplegia. This chapter will discuss the complexities of genetic testing and muscle biopsy for the evaluation of a possible metabolic myopathy.
A 68-Year-Old Female with Progressive Pain and Weakness
Authors: Cohen Jeffrey A. , Mowchun Justin J. , Lawson Victoria H. , Robbins Nathaniel M.
Published: November 2017

Statin myopathy can occur at anytime during use. This chapter discusses an approach to diagnosis, and emphasizes management considerations, including awareness of statin metabolism by the cytochrome P-450 system. A statin must be discontinued in any patient with evidence of myopathy or myalgias. A muscle biopsy should be done in cases that do not improve clinically or by creatine kinase level. It is important to note that there are cases of apparent statin myopathy which transform into a chronic autoimmune inflammatory myopathy. Antibodies to hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase have recently been identified in the majority of patients with autoimmune statin myopathy and this test may give further weight to treat with immunotherapy.
A 72-Year-Old Female with Facial Weakness and Droopy Eyelids
Authors: Cohen Jeffrey A. , Mowchun Justin J. , Lawson Victoria H. , Robbins Nathaniel M.
Published: November 2017

Fatigable weakness is the hallmark of myasthenia gravis (MG). It may present with false localizing signs leading to an itinal incorrect diagnosis of a brainstem stroke. MRI scanning of the brain with specific sequences can rule out the diagnosis of stroke. Differential diagnosis of MG may also include also motor neuron disease. Electromyography is very helpful in confirming the diagnosis of motor neuron disease. The two major diseases of the neuromuscular junction are MG and Lambert-Eaton syndrome (LEMS). A table presents the differing characteristics of each. LEMS can be associated with malignancy and MG with thyoma. Laboratory examinations have greatly assisted in differentiating these two conditions. There is specific antibody testing for each condition. Repetitive stimulation and single fiber electromyography also improve diagnostic acumen.
A 44-Year-Old Male with Subacute Onset of Syncope
Authors: Cohen Jeffrey A. , Mowchun Justin J. , Lawson Victoria H. , Robbins Nathaniel M.
Published: November 2017

Syncope in a patient with orthostatic hypotension (OH) may indicate autonomic dysfunction. The definition of OH is presented. Clinical features of parasympathetic and sympathetic function are discussed. The differential of acute autonomic dysfunction includes a number of conditions. An autoimmune etiology may occur autoimmune autonomic ganglionopathy. Serologic testing can assist in this diagnosis. If autoimmune immune modulating therapies may be indicated. Autonomic neuropathy may be a paraneoplastuc syndrome. Autonomic testing can also help with documenting autonomic neuropathy as well as the whether the defects are predominately parasympathetic or sympathetic. Amyloid should be considered as should diabetes but both have a more chronic course. An appropriate tissue biopsy with Congo Red staining can help to confirm the diagnosis of amyloid.
Arch Disease
Authors: Chong Ji Y. , Lerario Michael P.
Published: November 2017

Atherosclerosis of the ascending aorta and arch can potentially lead to high rates of embolic stroke. Evaluating plaque elements for complexity on transesophageal echocardiogram can help stratify this risk of stroke. Either antiplatelets or anticoagulants can be used for stroke prevention.
Hole in My Heart
Authors: Chong Ji Y. , Lerario Michael P.
Published: November 2017

The presence of a patent foramen ovale (PFO) is associated with cryptogenic stroke, especially in young patients. Medical therapy for patients with stroke and PFO includes antiplatelet therapy or anticoagulation. PFO closure is not routinely recommended for stroke prevention.
Driving Is a Headache
Authors: Chong Ji Y. , Lerario Michael P.
Published: November 2017

Headache and hemorrhagic infarcts in patients who are hypercoagulable (including pregnancy and puerperium) should prompt an evaluation for dural venous sinus thrombosis. Intracranial venous thrombosis is a rare cause of stroke. Diagnosis is made with venous imaging such as magnetic resonance venography. Investigation for underlying prothrombotic state is needed. Treatment is typically with anticoagulation, despite hemorrhage on imaging.
Can I Go Home Now?
Authors: Chong Ji Y. , Lerario Michael P.
Published: November 2017

Transient ischemic attack (TIA) is a risk factor for subsequent stroke. A TIA diagnosis should incorporate findings on brain MRI and noninvasive angiography, if available. Some patients with TIA are at high risk of early recurrence. Rapid evaluation and treatment reduce that risk. Some new data suggest that short-term dual antiplatelet therapy may reduce stroke recurrence in patients with TIA or minor stroke.
Cardiac Arrest
Authors: Chong Ji Y. , Lerario Michael P.
Published: November 2017

Hypoxic–ischemic brain injury is common following cardiopulmonary arrest and is associated with high rates of mortality and morbidity. Therapeutic hypothermia has been helpful in increasing survival and functional outcomes in these patients. The neurological examination, neuroimaging studies, and ancillary serological and neurophysiological testing can be helpful in prognostication post-arrest.
A Sickle Pickle
Authors: Chong Ji Y. , Lerario Michael P.
Published: November 2017

Sickle cell disease may result in large vessel intracranial stenoses, which cause high rates of stroke. Screening for elevated velocities on transcranial Dopplers is a good way to stratify stroke risk. Patients at high stroke risk should participate in an exchange transfusion program indefinitely to reduce the rate of subsequent stroke. Although there is a high risk of stroke in pediatric sickle cell patients, the use of IV tPA in this population is largely unstudied and not routinely recommended due to unclear safety and efficacy.
Recurrent Headaches
Authors: Chong Ji Y. , Lerario Michael P.
Published: November 2017

Cavernous malformations may cause intracerebral hemorrhage and seizures. Surgical resection is considered in patients with accessible lesions and recurrent hemorrhage or refractory seizures. However, current nonrandomized data suggest that nonsurgical treatment of these lesions may be superior. Cavernous malformations may be familial.
An Incidental Finding
Authors: Chong Ji Y. , Lerario Michael P.
Published: November 2017

Intracranial aneurysms may be detected incidentally on imaging. Location and size of an intracranial aneurysm are helpful in stratifying risk of hemorrhage. Risk stratification is important for treatment decision-making. Modifiable risk factors associated with aneurysm growth and rupture (hypertension and tobacco use) should be addressed. Treatment needs to be individualized. Small aneurysms may be monitored. Surgery has been associated with neurological disability and cognitive impairment. Endovascular coiling may be associated with a higher rate of incomplete obliteration. There are no randomized trial data in patients with unruptured aneurysms.
Introduction
Authors: Hari Riitta , Puce Aina
Published: November 2017

Neuronal communication in the brain is associated with minute electrical currents that give rise to both electrical potentials on the scalp (measurable by means of electroencephalography [EEG]) and magnetic fields outside the head (measurable by magnetoencephalography [MEG]). Both MEG and EEG are noninvasive neurophysiological methods used to study brain dynamics, that is temporal changes in the activation patterns, and sequences in signal progression. Differences between MEG and EEG mainly reflect differences in the spread of electric and magnetic fields generated by the same electric currents in the human brain. This chapter provides an overall description of the main principles of MEG and EEG and provides background for the following chapters in this and subsequent sections.
Basic Physics and Physiology of MEG and EEG
Authors: Hari Riitta , Puce Aina
Published: November 2017

This chapter outlines the general principles of physics and physiology underlying MEG and EEG signals. It introduces charges and electric currents, and the associated electric potentials and magnetic fields. Basic laws of electricity and the relationships between magnetic and electrical fields are examined. The phenomenon of superconductivity is introduced and related to measurements of MEG signals with SQUID sensors. The effects of various tissues and current configurations on MEG and EEG signals are described. Basic principles of source localization, that is modeling the neuronal sources of the observed MEG and EEG signals are described. The spatial accuracy versus precision of source localization is illustrated. Volume conduction, current spread in the different compartments of the body is explained.
Analyzing the Data
Authors: Hari Riitta , Puce Aina
Published: November 2017

This chapter focuses on MEG and EEG data analysis following artifact detection and removal. Basic time-domain analyses and issues related task-related data are initially examined. Analysis approaches for spontaneous activity and single-trial data in the time- and frequency-domains are introduced, including signal power, time–frequency and coherence analyses, cross-frequency coupling, connectivity, global field power, and dissimilarity of signal patterns. Source-modeling approaches are presented in detail, current dipoles versus distributed sources are compared, and head models are discussed. Spatial resolution and extent of neural sources are examined. The chapter concludes with a section devoted to common pitfalls in data analysis and interpretation.
Evoked and Event-Related Responses
Authors: Hari Riitta , Puce Aina
Published: November 2017

This chapter discusses general aspects of evoked and event-related responses in MEG and EEG recordings. The earliest evoked responses occur within milliseconds from stimulus onset (for example in the auditory brainstem) and cortical responses continue for many hundreds of milliseconds poststimulus. Sustained potentials and fields can be recorded during long-duration stimuli, or during tasks involving motor planning, attention, and other cognitive operations. Interstimulus interval and physical stimulus characteristics can dramatically affect amplitudes and latencies of evoked responses. A distinction is made between transient and steady-state responses. Various nomenclatures adopted in literature for different types of evoked responses are discussed and recommendations are given for more consistency in nomenclature.
Visual Responses
Authors: Hari Riitta , Puce Aina
Published: November 2017

This chapter introduces visual evoked responses. Transient VEPs are maximal across the posterior scalp and consist of three main deflections—N75, P100, and N135. Magnetic VEFs also show a prominent occipital response peaking at around 100 ms. Visual stimulation can include light flashes, pattern onset/offsets, pattern reversals and natural images. The extent and eccentricity of the visual stimulus can selectively encompass foveal or extrafoveal regions, or include quadrants, hemifield or the entire visual field. Stimulus attributes such as visual angle, spatial frequency, luminance and contrast greatly affect VEF and VEP amplitudes and latencies. Selective responses in the dorsal and ventral visual streams can be elicited with carefully chosen stimuli. Steady-state responses to periodically varying visual stimuli can be used to frequency-tag different aspects of the visual stimulus.
The Social Brain
Authors: Hari Riitta , Puce Aina
Published: November 2017

This chapter discusses MEG and EEG studies of social cognition and interaction. Our understanding in this field mainly derives from experiments using isolated verbal and visual social stimuli in highly controlled laboratory environments. However, normal social interaction occurs in a complex dynamic environment where behavior must be adapted and synchronized with partners. Consequently, set-ups have been developed to study brain functions during naturalistic interactions, even “hyperscanning” two brains at the same time in settings of two-person neuroscience, based on knowledge acquired in previous well-controlled laboratory studies where the participants were in a spectator role. This chapter discusses past studies of social cognition, action observation, mirroring, interaction, and emotional processing, and examines how future studies of social neuroscience might be conducted.
Looking to the Future
Authors: Hari Riitta , Puce Aina
Published: November 2017

This chapter looks to the future of MEG and EEG. Advances are expected both in instrumentation and in data-analysis tools suitable for experiments carried out in naturalistic settings. Moreover, the person’s behavior should be analyzed in much more finer detail than is done at present. Machine-learning approaches allow decoding of different brain states and distinctions between some patient and control groups; they also have implications for the development of brain–machine interfaces and brain-controlled prosthetic devices. Data governance will gain more emphasis when big brain-imaging datasets will be more widely available to the research community. At the same time, new challenges emerge for ensuring data quality, replicability, statistical analysis, documentation, and visualization. The main contribution of MEG and EEG to neuroscience continue to be in the accurate temporal information they provide.
Glut1 Deficiency and the Ketogenic Diets
Authors: Klepper Joerg
Published: November 2017

Glucose is the essential fuel for the brain. Transport into brain is exclusively mediated by the facilitative glucose transporter Glut1. Glut1 deficiency results in a “brain energy crisis,” causing global developmental delay, epilepsy, and complex movement disorders including paroxysmal nonepileptic events. Early-onset absence epilepsy, paroxysmal exertion-induced dystonia, and stomatin-deficient cryohydrocytosis have been recognized as variants. Diagnosis is based on phenotype, isolated low CSF glucose, and mutations in the SLC2A1 gene. The condition is treated effectively by classical ketogenic diets providing ketones as an alternative fuel for the brain. The modified Atkins diet in adolescents and adults improves palatability and compliance at the expense of lower ketosis. Dietary treatment is continued into adolescence to meet the energy demand of the developing brain, raising concerns about long-term adverse effects. Current fields of research include novel compounds such as ketoesters and genetic approaches in Glut1-deficient mice as potential treatment options.
Ketogenic Diet in Established Epilepsy Indications
Authors: Bergin Ann M.
Published: November 2017

The ketogenic diet is a metabolic therapy that provides an alternative strategy for seizure control in medication-resistant epilepsy. Many decades of continued use of diet therapy, amassing consistent observational evidence, was recently supported by a randomized, controlled study indicating benefit of diet treatment in children with refractory epilepsy as compared with a control group who continued with standard of care and delayed diet treatment for three months. Well-established uses include children with refractory, nonsurgical epilepsies and epileptic encephalopathies including infantile spasms and West syndrome, Lennox Gastaut syndrome, and Dravet and Doose syndromes. Current knowledge on the efficacy and role of diet therapy in these conditions are discussed.
The Ketogenic Diet and Related Therapies in “Novel” Situations
Authors: Kessler Sudha Kilaru
Published: November 2017

The ketogenic diet (KD) is often considered as a treatment option for medication-resistant focal epilepsies and symptomatic generalized epilepsies, but is perhaps less commonly considered for idiopathic generalized epilepsies. The evidence for the use of the KD in two common idiopathic generalized epilepsy syndromes, childhood absence epilepsy and juvenile myoclonic epilepsy, is presented here.
Ketogenic Diet in Status Epilepticus
Authors: Nabbout Rima
Published: November 2017

Refractory status epilepticus (RSE) is associated with a significant risk of death or neurological morbidity. The ketogenic diet (KD) is a dietary therapy that succeeds in controlling seizures in otherwise RSE in children and adult patients. Inflammatory etiologies might be a particular target, but KD has reported efficacy in other etiologies. KD is well tolerated, and the effect is seen within days. Randomized and controlled studies are lacking in this area, and studies are needed to prove the efficacy of KD in RSE and to identify specific indications. This would help to increase its use and to implement it in intensive care units to resolve severe epileptic conditions quickly.
Metabolism-Based Treatments to Counter Cancer
Authors: Seyfried Thomas N. , Shelton Laura M.
Published: November 2017

Accumulating evidence indicates that cancer is a type of mitochondrial metabolic disease. Chronic damage to mitochondria causes a gradual shift in cellular energy metabolism from respiration to fermentation. Consequently, fermentable metabolites become the drivers of cancer. Mitochondrial injury can explain the long-standing “oncogenic paradox,” and all major hallmarks of cancer including genomic instability. Restriction of fermentable fuels therefore becomes a viable therapeutic strategy for cancer management. The ketogenic diet (KD) is a metabolic therapy that lowers blood glucose and elevates blood ketone bodies. Ketone bodies are a “super fuel” for functional mitochondria, but cannot be metabolized efficiently by tumor mitochondria. The efficacy of KDs for cancer management can be enhanced when used together with drugs and procedures (such as hyperbaric oxygen therapy) (that further target fermentation. Therapeutic ketosis can represent an alternative, nontoxic strategy for managing and preventing a broad range of cancers while reducing healthcare costs.
Ketogenic Diet as Adjunctive Therapy for Malignant Brain Cancer
Authors: Woolf Eric C. , Scheck Adrienne C.
Published: November 2017

Malignant brain tumors are devastating, and increased survival requires new therapeutic modalities. Metabolic dysregulation results in an increased need for glucose in tumor cells, suggesting that reduced tumor growth could be achieved with decreased glucose availability either through pharmacological means or use of a high-fat, low-carbohydrate ketogenic diet (KD). KD provides increased blood ketones to support energy needs of normal tissues and has been shown to reduce tumor growth, angiogenesis, inflammation, peritumoral edema, migration, and invasion. Furthermore, this diet can enhance the activity of radiation and chemotherapy in a mouse model of glioma, thus increasing survival. In vitro studies indicate that increasing ketones in the absence of glucose reduction can also inhibit cell growth and potentiate the effects of radiation. Thus, emerging data provide strong support for the use of KD in the treatment of malignant gliomas and thus far has led to a limited number of clinical trials.
Metabolic Therapy for Autism Spectrum Disorder and Comorbidities
Authors: Cheng Ning , Masino Susan A. , Rho Jong M.
Published: November 2017

Autism spectrum disorder (ASD) is a heretogenous developmental disorder characterized by deficits in sociability and communication and by repetitive and/or restrictive behaviors. Currently, only comorbid manifestations can be alleviated (such as seizures and sleep disturbance) not core behavioral symptoms. Recent studies have increasingly implicated mitochondrial dysfunction as a cause of ASD. Mitochondria play an integral role in many cellular functions and are susceptible to many pathophysiological insults. Derangements in mitochondrial structure and function provide a scientific rationale for experimental therapeutics. Meanwhile, the high-fat, low-carbohydrate ketogenic diet (KD) has been shown to enhance mitochondrial function through a multiplicity of mechanisms. Reviewed herein is clinical and basic laboratory evidence for the use of metabolism-based therapies such as the KD in the treatment of ASD, as well as emerging comorbid models of epilepsy and autism. Future research directions aimed at validating such therapeutic approaches and identifying novel mechanistic targets are discussed.
Dietary Therapy for Neurological Disorders
Authors: Stafstrom Carl E.
Published: November 2017

Dietary and metabolic therapies such as the high-fat, low-carbohydrate ketogenic diet (KD) are best known for the treatment of intractable epilepsy. Yet, dietary and metabolic approaches have also found some efficacy in a wide variety of other neurological diseases, including autism spectrum disorder, brain trauma, Alzheimer’s disease, sleep disorders, brain tumors, pain, and multiple sclerosis, as discussed in other chapters of this volume. This chapter provides an overview of clinical and experimental studies using the KD in an array of other neurologic disorders: amyotrophic lateral sclerosis, Parkinson’s disease, mood disorders, and migraine. Despite the wide spectrum of pathophysiological mechanisms underlying these disorders, it is possible that one or more final common metabolic pathways might be influenced by dietary intervention. There is compelling albeit preliminary evidence that correction of aberrant energy metabolism through dietary manipulation could favorably influence diverse neurological diseases.
Ketogenic Diet in a Hippocampal Slice
Authors: Kawamura Masahito
Published: November 2017

The hippocampus is thought to be a good experimental model for investigating epileptogenesis in and/or antiepileptic therapy for temporal lobe epilepsy. The hippocampus is also a useful target for researching the ketogenic diet. This chapter focuses on electrophysiological recordings using hippocampal slices and introduces their use for studying the anticonvulsant effects underlying ketogenic diets. The major difficulty in using hippocampal slices is the inability to precisely reproduce the in vivo condition of ketogenic diet feeding in this in vitro preparation. Three different approaches are reported to reproduce diet effects in the hippocampal slices: (1) direct application of ketone bodies, (2) mimicking the ketogenic diet condition with whole-cell patch-clamp technique, and (3) hippocampal slices from ketogenic diet–fed animals. Significant results have been found with each of these methods. These three approaches are useful tools to elucidate the underlying anticonvulsant mechanisms of the ketogenic diet.
Ketogenic Diet, Adenosine, Epigenetics, and Antiepileptogenesis
Authors: Lusardi Theresa A. , Boison Detlev
Published: November 2017

Epilepsy is common, affecting about 1% of the population. Conventional treatments are ineffective in about one third of patients, and current therapies do not prevent epilepsy or its progression. For individuals with drug-refractory epilepsy the ketogenic diet (KD) can provide seizure relief in approximately fifty percent of patients, with complete and permanent remission in some cases, suggesting possible antiepileptogenic effects of the diet. Whereas mechanisms underlying antiseizure effects of KD have been identified, mechanistic links between KD therapy and antiepileptogenesis constitute a novel area of research. An adenosine receptor-mediated role of KD therapy in seizure suppression is well established, and recent evidence demonstrates that the KD regulates adenosine homeostasis in the brain. Adenosine in turn has previously unappreciated epigenetic functions as a regulator of DNA methylation. This chapter discusses recent evidence that KD influences the epigenome through modulation of adenosine metabolism as a plausible antiepileptogenic mechanism of the diet.
Alzheimer’s Disease
Authors: Veech Richard L. , King M. Todd
Published: November 2017

Deficits in cerebral glucose utilization in Alzheimer’s disease (AD) arise decades before cognitive impairment and accumulation of amyloid plaques and neurofibrillary tangles in brain. Addressing this metabolic deficit has greater potential in treating AD than targeting later disease processes – an approach that has failed consistently in the clinic. Cerebral glucose utilization requires numerous enzymes, many of which have been shown to decline in AD. Perhaps the most important is pyruvate dehydrogenase (PDH), which links glycolysis with the Krebs cycle and aerobic metabolism, and whose activity is greatly suppressed in AD. The unique metabolism of ketone bodies allows them to bypass the block at pyruvate dehydrogenase and restore brain metabolism. Recent studies in mouse genetic models of AD and in a human Alzheimer’s patient showed the potential of ketones in maintaining brain energetics and function. Oral ketone bodies might be a promising avenue for treatment of Alzheimer’s disease.
Mitigation of Damage from Reactive Oxygen Species and Ionizing Radiation by Ketone Body Esters
Authors: Curtis William , Kemper Martin , Miller Alexandra , Pawlosky Robert , King M. Todd , Veech Richard L.
Published: November 2017

Reactive oxygen and nitrogen species, ROS and RNS, are ubiquitous in living cells. They have beneficial effects but are also the cause of a wide variety of diseases. However adding excessive amounts of reducing agents has a long history of clinical failure. This problem can be overcome by providing a novel ester of D-beta-hydroxybutyrate–R-1,3-butanediol, which is rapidly hydrolyzed to ketone bodies, the metabolism of which leads to the production of NADPH. The free cytosolic [NADP+]/[NADPH] redox potential is the most negative in the cell and sets the potential of the glutathione and ascorbic acid couples. Ketone bodies also act by inhibiting histone deacetylases, activating the transcription factor FOXO3 and increasing the transcription of enzymes involved in the destruction of ROS. Ketone esters would be effective in the treatment of a variety of disparate diseases where ROS play a role, ranging from Parkinson’s disease to radiation sickness and aging.
Effects of the Ketogenic Diet on the Blood-Brain Barrier
Authors: Banjara Manoj , Janigro Damir
Published: November 2017

Ketone bodies (KBs) are always present in the blood, and their levels increase after high-fat diet intake, prolonged exercise, or extended fasting. Thus, one can predict effects on the brain capillary endothelium from high levels of ketones in the blood. Prolonged exposure of blood-brain barrier (BBB) endothelial cells to KBs induces expression of monocarboxylate transporters and enhances brain uptake of KBs. In addition, cell migration and expression of gap junction proteins are up-regulated by KBs. Thus, beneficial effects of the ketogenic diet may depend on increased brain uptake of KBs to match metabolic demand and repair of a disrupted BBB. As the effects of KBs on the BBB and their transport mechanisms across the BBB are better understood, it will be possible to develop alternative strategies to optimize the therapeutic benefits of KBs for brain disorders where the BBB is compromised.
Ketone Supplementation for Health and Disease
Authors: Poff Angela M. , Kesl Shannon L. , D’Agostino Dominic P.
Published: November 2017

Exogenous ketone supplements rapidly elevate blood ketones in a dose-dependent manner regardless of dietary intake, making them a practical method of inducing therapeutic ketosis for medical use. It is thought that ketone supplementation could be used as a stand-alone therapy, or as a way to further augment the therapeutic efficacy of the ketogenic diet. Ketone supplementation could increase treatment compliance by allowing many patients to maintain a more normal lifestyle with a less restrictive diet. The therapeutic effects of ketone supplementation are likely mediated in part by a stabilization of blood glucose and insulin levels, an increase in metabolic efficiency, and an inhibition of oxidative stress and inflammation. Ketone supplements may also serve as an effective preventative medicine due to their potential ability to protect and enhance mitochondrial health and function. Indeed, preliminary evidence suggests there are a number of conditions for which exogenous ketone supplementation may be beneficial.
2-Deoxyglucose
Authors: Stafstrom Carl E. , Sutula Thomas P.
Published: November 2017

Metabolic regulation of excitability is increasingly appreciated as a strategy to control seizures and reduce pathogenesis. Inhibiting or bypassing glycolysis may be one way in which the ketogenic diet suppresses seizures. 2-deoxy-D-glucose (2DG) is a glucose analog that partially inhibits glycolysis and has antiseizure effects in several acute and chronic seizure models. The mechanisms underlying the acute and chronic effects of 2DG are being investigated. Preliminary studies provide evidence that the acute anticonvulsant actions of 2DG involve activity-dependent presynaptic suppression of excitatory synaptic transmission during network synchronization. The chronic effects of 2DG entail reduction of the expression of brain-derived neurotrophic factor and its receptor, tyrosine kinase B. Preclinical toxicology studies demonstrate that 2DG has a favorable toxicity profile at doses effective for seizure protection. Currently available preclinical studies support 2DG as a novel first-in-class metabolic treatment for epilepsy with an antiglycolytic mechanism distinct from all other anticonvulsants.
Breuer Discovers How the Balance Portion of the Inner Ear Works
Authors: Baloh Robert W.
Published: November 2017

Josef Breuer presented his initial work on the inner ear to the Imperial Society of Physicians in 1873. His basic premise was that the semicircular canals sense angular movement of the head by movement of the fluid (endolymph) within them. The endolymph moves relative to the walls of the canals because of its inertia. In dissecting the semicircular canals of pigeons, he noted nerve endings contacting cells at the base of the ampulla and microscopic hairs extending from the top of the cells into a gelatinous bulb (the cupula). He hypothesized that movement of the endolymph fluid triggered by angular head movements bent the tiny hairs, activating the nerve endings at the base of the hair cells. The nerves in turn passed on signals reflecting the direction and magnitude of hair deflection to the central nervous system. At approximately the same time, Ernst Mach came to a similar conclusion.
The War Years and Bárány’s Decision to Leave Vienna
Authors: Baloh Robert W.
Published: November 2017

As the conflict in Adam Politzer’s clinic heated up and with the approach of World War I, Robert Bárány volunteered for service in the army medical corps, in keeping with his pacifist ideas. Although he could have been excused from military service because of his ankylosed knee, Bárány was swept up in the wave of patriotism prevalent in Vienna. He was immediately assigned as an army surgeon to a hospital in the fortress of Przemysl near the Russian border. Przemysl was eventually overrun by Russian troops, and Bárány was transported along with more than 100,000 other prisoners in cattle cars across the Russian steppe to Turkistan. It was during his stay in Russia that Bárány received the exciting news from the Swedish minister in St. Petersburg that he had been awarded the 1914 Nobel Prize in Medicine for his work on the caloric reaction.
Bárány’s Test Battery and the First Description of Benign Paroxysmal Positional Vertigo
Authors: Baloh Robert W.
Published: November 2017

Robert Bárány developed an extensive battery of clinical tests of the vestibular system, most of which he outlined in his 1907 book on the physiology and pathology of the vestibular system. The basic concepts of his examination were to use the oculomotor responses (nystagmus) and postural responses (balance and past-pointing) to determine the functional status of the inner ear. Most of his work on the vestibular system was published in Vienna prior to his move to Uppsala, Sweden, after World War I. In Uppsala, he described several surgical techniques, including an operation to produce a fistula in the wall of the horizontal semicircular canal to improve hearing in patients with otosclerosis. Probably the most important article he wrote while in Uppsala was a paper published in 1921 describing a young woman with positional vertigo and nystagmus. This was the first detailed description of nystagmus associated with benign paroxysmal positional vertigo.
Bárány’s Life in Uppsala and His Work with Lorente de Nó
Authors: Baloh Robert W.
Published: November 2017

Lorente de Nó came to Uppsala, Sweden, in 1924 to work with Robert Bárány, with the goal of studying the central nervous system pathways of the vestibular nystagmus response. Bárány’s 1907 book described a patient with a lesion involving the reticular formation of the pons close to the abducens nucleus who could generate only the slow phase of nystagmus. With stimulation, the patient’s eyes slowly deviated to one side and became pinned. The patient also had a loss of voluntary eye movements. Bárány concluded that there must be separate centers in the brainstem for the production of the slow and fast phases of nystagmus. He speculated that the center for generating fast phases was in the reticular substance next to the abducens nucleus and that this component was under the influence of cortical control. Nó would go on to perform studies of these central pathways for generating nystagmus in rabbit.
Hallpike Defines the Syndrome of Benign Paroxysmal Positional Vertigo
Authors: Baloh Robert W.
Published: November 2017

In 1952, Charles Hallpike and Margaret Dix published a paper in which they described the clinical profile of three of the most common causes of vertigo—Ménière’s disease, vestibular neuronitis, and benign paroxysmal positional vertigo (BPPV). Their strategy was simple: First, identify the symptoms and natural history of the disease, then document the physical signs associated with the disease, and finally, when possible, correlate the clinical features with histological studies of the temporal bones. They provided the first clear clinical description and the first pathology associated with the syndrome of BPPV. They described the clinical features of a large number of cases they had seen in the Queen Square clinic. They concluded that positional nystagmus of the benign paroxysmal type, first described by Robert Bárány in 1921, was due, as Bárány believed, to otolith disease.
Schuknecht and His Breakthrough on Benign Paroxysmal Positional Vertigo
Authors: Baloh Robert W.
Published: November 2017

In 1949, Harold Schuknecht completed his residency in John Lindsay’s Otolaryngology Department at the University of Chicago and stayed first as a clinical instructor and then as an assistant professor. Schuknecht reviewed the temporal bone specimens from the patient reported by his mentor, John Lindsay, and from patients reported by Charles Hallpike and colleagues and was struck by the similarity in the pathologic changes. He concluded that in each case damage to the labyrinth resulted from occlusion of the anterior vestibular artery. Schuknecht believed that the delayed positional vertigo that occurred in these cases must have originated from the posterior semicircular canal. He reasoned that with degeneration of the superior vestibular labyrinth, otoconia would be released from the otolithic membrane of the utricular macule and that, in certain positions of the head, the otoconia would respond to gravity and thereby activate the cupula of the posterior semicircular canal.
Conclusions
Authors: Baloh Robert W.
Published: November 2017

Looking back, all the key information for understanding the mechanism of benign paroxysmal positional vertigo (BPPV) was known early in the 20th century, but it was not until the end of the century that a cure was discovered. Karl Wittmaack’s experiments were interrupted by World War I and were never published. Robert Bárány described the characteristic stereotyped appearance of the nystagmus associated with BPPV, and Charles Hallpike provided convincing evidence that BPPV was a benign condition originating from the inner ear, but both misinterpreted the nystagmus as originating from the gravity-sensing utricular macule. Harold Schuknecht focused attention on the posterior semicircular canal and otolithic debris, but his cupulolithiasis model failed to explain many of the typical features of the nystagmus. Not surprisingly, early treatment maneuvers based on the cupulolithiasis mechanism were not very effective. Understanding the canalithiasis model was the key to developing effective treatment maneuvers.
Falling All the Time
Authors: Walsh Richard A.
Published: November 2017

Progressive supranuclear palsy is a four-repeat tauopathy that is confirmed, like all neurodegenerative disease, at postmortem examination. An expanding group of clinical syndromes are now linked with this pathology in its early stages, although with disease progression there tends to be greater clinical similarity with the classical Richardson’s syndrome, an akinetic rigid form of parkinsonism with a progressive supranuclear gaze palsy and prominent frontal cognitive impairment. Currently, there are no disease-modifying therapies for progressive supranuclear palsy; however, there continues to be interest in immunotherapies targeted at tau pathology. Liaison with colleagues with an interest in palliative neurology is appropriate for patients in the advanced stages of the disease.
A New Loss of Order
Authors: Walsh Richard A.
Published: November 2017

The priority in the investigation of sporadic adult-onset ataxia is to identify potentially treatable causes, to improve gait or to reduce risk of recurrence. Disorders such as multiple sclerosis, alcohol-related cerebellar degeneration, and vitamin B12 deficiency are far more common than rarer causes such as paraneoplastic syndromes or recessive genetic disorders. Routine biochemistry, magnetic resonance imaging, and cerebrospinal fluid studies are typically performed as part of the workup to guide any further intervention and investigations. Advances in genetic testing using next-generation sequencing are revealing that many patients with presumed nongenetic sporadic ataxias have a genetic cause for their symptoms. Expert opinion to guide genetic testing in cases in which no alternative cause of ataxia is found is advisable.
Falls
Authors: Fox Susan H.
Published: November 2017

Frontal lobe gait disorders are characterized by a pattern of gait that is not explained by extrapyramidal or pyramidal dysfunction with dyspraxic features reflecting a “higher order” difficulty with the coding of the pattern of movement required for normal gait rather than the subcortical control of gait or the pyramidal final common pathway. Magnetic resonance imaging is the most useful single investigation that tends to reveal vascular or neurodegenerative etiologies, with the less common normal pressure hydrocephalus being the one treatable cause that should not be missed. The majority of higher order frontal lobe gait disorders are not treatable and patients require a wheelchair for safety.
A Tremor with an Abnormal Posture
Authors: de Bie Robertus M. A. , Ten Holter Susanne E. M.
Published: November 2017

Dystonic tremors are a commonly misdiagnosed group of primary tremor disorders, typically mistaken for Parkinson’s disease or essential tremor. Like most movement disorders, this is a clinical diagnosis, so the overlap in some features between all of these disorders can be confusing to less experienced and even more experienced physicians. A tremor in the presence of a dystonia is a dystonic tremor syndrome, regardless of the clinical features. Treatment of dystonic tremor can be challenging without the same gratifying response seen to levodopa in tremor associated with Parkinson’s disease or to beta-blockers and primidone in essential tremor. Deep-brain stimulation remains an option in the most disabling cases.
“I Have Never Seen Anything Like It Before”
Authors: Walsh Richard A.
Published: November 2017

Functional movement disorders represent up to 20% of cases referred to some movement disorders clinics. The longer the symptoms are present,, the lower the success rate in resolving functional syndromes. A good knowledge of the positive features on clinical examination that facilitate an early diagnosis is important. Psychiatric or psychological factors need not be present at the time of presentation to make a diagnosis of functional disease. This assists in the diagnosis and may allow closer and valuable involvement from psychiatry colleagues. Close and primary involvement of a neurologist to allow a diagnosis to be made in a timely manner to avoid unnecessary investigations is important.
Could It Possibly Be … ?
Authors: Fox Susan H.
Published: November 2017

There is increasing recognition of adult presentations of metabolic diseases typically associated with children. These phenotypes are often milder and potentially mistaken for more common adult-onset disorders, therefore requiring a high index of suspicion. The most common adult-onset clinical features involve focal dystonias and parkinsonism. Making a diagnosis of dopa-responsive dystonia in an adult typically involves a therapeutic trial of low-dose levodopa. Genetic testing may be useful to confirm dopa-responsive dystonia and rule out other causes of dystonia and tremor. The neurological examination should be performed carefully to ensure that subtle dystonia is not missed. A trial of levodopa may be warranted to ensure that late-onset dopa-responsive dystonia is not missed.
Always Worth a Second Look
Authors: Walsh Richard A.
Published: November 2017

The serotonin syndrome is a toxic syndrome resulting from excessive stimulation of central 5-HT1A and 5-HT2A receptors. This is most commonly an iatrogenic syndrome, which in its most severe form can be fatal. It is more common for milder forms to present, and there is increasing recognition of serotoninergic drugs that can give rise to serotonin syndrome when used in combination. It is essential for physicians to be familiar with the clinical features of serotonin toxicity and similar syndromes discussed in this chapter that are marked by altered awareness, autonomic instability, changes in muscle tone, and pyrexia. Withdrawal of the drug(s) believed to be responsible and supportive care are the primary therapeutic steps.
An Introductory Snapshot
Authors: Aminoff Michael J.
Published: November 2017

The name of Charles Bell has been given to a nerve, a facial palsy, a clinical sign, an involuntary muscle spasm, a muscle, and a fundamental law of physiology, making it well known to physicians, surgeons, and medical students alike, even though they generally have little knowledge or appreciation of his actual, very solid accomplishments. He suggested, in fact, new ways to look at—and to make sense of—the nervous system. Bell was revered by some contemporaries for his achievements; to others, however, his name and brilliance were tarnished by charges of intellectual dishonesty and fraud. This chapter introduces Charles Bell, summarizing his achievements and failings so that the reader has a general understanding of the subject of this biography. He is considered as a scientist–surgeon, as a clinician–educator, and as a polymath.
To Each His Due
Authors: Aminoff Michael J.
Published: November 2017

Charles Bell died in 1842. Many of his achievements have been forgotten, but they were nevertheless substantial. Physicians and surgeons know of him primarily because of the facial weakness and its associated signs named after him. New generations of scientists and educators, of surgeons and artists, should bear in mind the foundations on which they themselves build, but they should avoid the mistakes made by Bell. His quarrels with others over priority for certain discoveries, and the alteration of his previously published papers to support his claims, should be recalled—if at all—with regret for the behavior that marred an otherwise exceptional career. He was a brilliant but flawed human being who contributed much to the advance of knowledge.
Brain Tumors
Authors: Eseonu Chikezie , Rincon-Torroella Jordina , Quiñones-Hinojosa Alfredo
Published: November 2017

Brain tumor cases make up a significant part of the neurosurgery Oral Board Exam. A multitude of brain tumors exist and can be intraaxial or extraaxial. When considering a differential diagnosis for a brain lesion, infection, hematomas, infarctions, thrombosed aneurysms, inflammation, and demyelinating disease must be considered in addition to tumors. Common adult brain tumors consist of gliomas, meningiomas, metastases, and pituitary tumors. Management of brain tumors consists of understanding preoperative care, indications for surgery, surgical approaches, interpretation of preoperative and postoperative imaging, intraoperative and postoperative complications, and the role of adjuvant therapy, including chemotherapy and radiotherapy. Reviewing these essential points for the most common brain tumor cases and mastering the current treatment recommendations for common tumors will also be helpful for the boards.
Cranial Trauma and ICU Management
Authors: Simonds Gary
Published: November 2017

Head trauma is a commonly encountered diagnostic problem in neurosurgery and is thought by some to be relatively limited in its technical challenges—as such, it gives the examinee an opportunity to excel in this area. Six cases are presented, and each case includes the history and physical examination, imaging studies, analysis of case and treatment plan, and complications.. Cases include closed head injury with raised intracranial pressure, gunshot wound to the head, epidural hematoma, subdural hematoma, trauma with intracerebral hemorrhage, sinus thrombosis, and a depressed skull fracture. Sample questions and reasonable answers are also provided, with discussion that covers a wide range of treatment options.
Peripheral Nerve
Authors: Spinner Robert J.
Published: November 2017

Peripheral nerve is an important and historical part of neurosurgery. It also has been a major focus of both the written and oral examinations administered by the American Board of Neurological Surgeons (ABNS). The Oral Board candidate must be prepared for potentially one to several questions on some of the common disorders of the peripheral nervous system. In this chapter, a systematic approach to peripheral nerve problems is presented. Common areas that might be examined include tumors, injuries, inflammatory conditions, entrapments, and neuropathic pain. Five cases are illustrated, and “pearls” are provided. At the conclusion of the chapter are nine photographs representing problems the Oral Board candidate should be able to identify and answer.