bluuebunny/crossref_metadata_2025 huggingface dataset:
Adult Hippocampal Neurogenesis, Pattern Separation, and Generalization
Authors: Klemenhagen Kristen C. , Schneier Franklin R. , Fyer Abby J. , Simpson H. Blair , Hen René
Published: November 2017

Almost one-third of adult Americans will have an anxiety disorder in their lifetime, with enormous personal, societal, and financial costs. Among the most disabling of these disorders are post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), social anxiety disorder, generalized anxiety disorder, and panic disorder. Although there are evidence-based treatments for these disorders, as many as 50% of patients do not respond, and there is a considerable need for new therapies. This chapter proposes that the excessive generalization seen in patients with pathological anxiety is due to impaired hippocampal functioning, specifically a deficit in the neural process of pattern separation, which relies upon the dentate gyrus and is sensitive to neurogenesis. Preclinical findings indicate that stimulating DG neurogenesis improves pattern separation and reduces anxiety behaviors in mice. As a result the authors hypothesize that pharmacological or environmental manipulations aimed at stimulating neurogenesis will be beneficial for the treatment of anxiety disorders.
Secondary Messenger Systems in PTSD
Authors: Schmidt Ulrike
Published: November 2017

Second messengers such as cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), inositoltriphosphate, and diacylglycerol (DAG) are a prerequisite for the signal transduction of extracellular receptors. The latter are central for cellular function and thus are implicated in the pathobiology of a variety of disorders, such as schizophrenia, bipolar disorder, major depression, and post-traumatic stress disorder (PTSD). This chapter focuses on the involvement of second messenger molecules and their regulators as direct targets in human and animal PTSD and aims to stimulate the underdeveloped research in this field. The synthesis of literature reveals that second messengers clearly play a central role in PTSD-associated brain regions and processes. In particular, pituitary adenylate cyclase-activating polypeptide (PACAP), an important regulator of intracellular cAMP levels, as well as protein kinase c, the major target of DAG, belong to the hitherto most promising PTSD candidate molecules directly involved in second messenger signaling.
Fluid Biomarkers Indicative of Neurodegenerative Diseases
Authors: Zetterberg Henrik , Schott Jonathan M.
Published: November 2017

A major unifying feature of neurodegenerative diseases (NDDs) is excessive neuronal loss. Depending on when and where this occurs, patients may express distinct neurological and psychiatric symptoms. Neurodegeneration is accompanied by protein aggregation, inflammation, and microglial activation that may be drivers of the disease or in some circumstances may be protective reactions to the neurodegenerative process. A key development over the past decade has been our ability to leverage these accompanying central nervous system changes to develop clinically impactful biomarkers of specific NDDs. This has been crucial in helping us develop an understanding the time line of progression of these diseases, in their early diagnosis and to help target patients appropriately in therapeutic clinical trials, This chapter gives an overview of both established and novel fluid biomarkers for neurodegeneration, protein accumulation, inflammation, and microglial activation across different neurodegenerative diseases. Common as well as disease-specific biomarker changes in cerebrospinal fluid and blood are emphasized.
Predementia Disorders
Authors: Pillai Jagan A.
Published: November 2017

Neurodegenerative disorders (NDDs) are currently conceptualized as proteinopathies with a long trajectory of pathological changes preceding the onset of clinical symptoms by over a decade. Predementia, the stage of disease before onset of clinical symptoms and dementia where significant irreversible neuronal damage and cognitive decline have yet to occur, is seen as a promising stage to target for a new generation of therapeutic interventions. This chapter reviews the growing understanding of the predementia stages across NDDs and some of the developing challenges to the present clinical characterization of the predementia stage. It further surveys the clinical trials being currently undertaken across NDDs in this domain.
Cell Culture, iPS Cells and Neurodegenerative Diseases
Authors: Nat Roxana , Eigentler Andreas
Published: November 2017

Somatic reprogramming technology, which enables the conversion of adult human non-neural cells into neurons, has progressed rapidly in recent years. The derivation of patient-specific induced pluripotent stem (iPS) cells has become routine. The inherent broad differentiation potential of iPS cells makes possible the generation of diverse types of human neurons. This constitutes a remarkable step in facilitating the development of more appropriate and comprehensive preclinical human disease models, as well as for high throughput drug screenings and cell therapy. This chapter reviews recent progress in the human iPS cell culture models related to common and rare NDDs, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, spinal muscular atrophy, and degenerative ataxias. It focuses on the pathophysiological features revealed in cell cultures, and the neuronal subtypes most affected in NDDs. The chapter discusses the validity, limitation, and improvements of this system in faithfully and reproducibly recapitulating disease pathology.
Cancer Screening in Japan
Authors: Quelch John A. , Rodriguez Margaret L.
Published: November 2017

How do we persuade consumers to engage in short and long-term behaviors that are in their self-interest? This chapter focuses on different messaging approaches to persuade consumers to invest time and money in taking preventive actions and also to adhere to their doctors’ advice, once given (for example, by adhering to a prescription regimen).
“Dumb Ways to Die”
Authors: Quelch John A.
Published: November 2017

How do we persuade consumers to engage in short and long-term behaviors that are in their self-interest? This chapter focuses on different messaging approaches to persuade consumers to invest time and money in taking preventive actions and also to adhere to their doctors’ advice, once given (for example, by adhering to a prescription regimen).
23andMe
Authors: Quelch John A. , Rodriguez Margaret L.
Published: November 2017

As more emphasis is placed on consumer engagement and empowerment in the health care arena there are some who wish to control or nudge consumer behavior in the “right” direction, especially if they perceive consumers to be insufficiently educated to handle the new information available to them.
Introduction
Authors: Montgomery Erwin B.
Published: November 2017

Even by the standards at the time of the first edition, programming for some patients can still be a challenge. Even with the old systems, there were literally thousands of possible combinations of stimulator parameters which often intimidates programmers. The increase in functionality, such as multiple stimulation patterns and interleaved electrode configurations, has exponentially increased the number of combinations of DBS settings. Fortunately, most patients respond to a similar and narrow range of combinations, provided that the DBS stimulating leads are optimally placed. For other patients, however, dedicated effort is required to identify the optimal combination. The greatest danger for patients is that programmers will give up too soon. The premise of this text is that post-operative DBS programming can be made more effective and efficient by knowing some basic electrophysiological principles and some details of neuroanatomy.
Principles of Electrophysiology
Authors: Montgomery Erwin B.
Published: November 2017

In many ways, post-operative DBS programming is “prescribing electricity” in much the same sense as “prescribing medications.” The principles of pharmacokinetics and pharmacodynamics that guide the rational use of medications find parallels in DBS. Many drugs have their effect by binding to ligand-gated channels, particularly channels that control the flow of electrical charges, in the form of ions across the cell membrane of the neuron in the soma. The binding of drugs to receptors can open the receptor to approximate the normal opening by endogenous neurotransmitters, or to block the channel from opening when endogenous neurotransmitters are released. In the case of DBS, the electrical charges manipulated in the nervous system similarly affect neuronal membrane channels; however, these initially and primarily are voltage gated ionic conductance channels, which are described in detail in this chapter.
Approach to DBS in the Vicinity of the Subthalamic Nucleus
Authors: Montgomery Erwin B.
Published: November 2017

The regional anatomy around the DBS lead in the subthalamic nucleus (STN) determines efficacy and adverse effects. Understanding the regional anatomy allows the programmer to adjust the stimulation to provide optimal benefit and the absence of adverse effects.The STN lies near the junction of the diencephalon and mesencephalon. It is just ventral to the thalamus, just lateral to the brachium conjunctivum and red nucleus, and medial and dorsal to the internal capsule. These structures are important because inappropriate stimulation causes side effects. For examples: Electrical fields spreading to ascending sensory medial lemniscus and spinothalamic pathways behind the STN produce paresthesias. Inadvertent stimulation of the brachium conjunctivum can cause ataxia and loss of balance. The red nucleus lies in the brachium conjunctivum, and the exiting axons from the oculomotor nucleus run within the red nucleus. Electrical fields spreading to these structures can result in disconjugate gaze and diplopia. Stimulating the internal capsule laterally or dorsally can cause tonic muscle contractions.
Approach to DBS in the Vicinity of the Globus Pallidus Interna
Authors: Montgomery Erwin B.
Published: November 2017

The regional anatomy around the DBS lead in the globus pallidus interna (GPi) determines efficacy and adverse effects. Understanding the regional anatomy allows the programmer to adjust the stimulation to provide optimal benefit and the absence of adverse effects. Just ventral to the sensorimotor region of the GPi is the optic tract. Spread of stimulation to the optic tract can produce phosphenes (the experience of seeing light without light actually entering the eye). The internal capsule lies just posterior to the globus pallidus, and stimulation there can cause tonic muscle contractions. Anteriorly lies the non-motor region, and stimulation of this region could cause changes in cognition and personality, although the incidences of these problems is much less that with STN DBS. This chapter discusses the regional anatomy of the GPi segment, adverse effects from malpositioning of DBS leads, approaches to GPi DBS for Parkinson’s, treating dystonia with DBS of the GPi, and treating hyperkinetic disorders.
Helpful Programming Hints
Authors: Montgomery Erwin B.
Published: November 2017

A number of suggestions are offered to make the post-operative care of patients with implanted systems more effective and safe. The choice of constant current versus constant voltage stimulation and the consequences and implications of that choice are reviewed. For example, with constant voltage stimulation, the programmer should wait at least two weeks after lead implantation before programming the IPG. Starting DBS too soon after implantation can cause marked adverse effects because of changes in tissue impedance is high immediately after implantation. The use of a monopolar survery at the initiation of DBS is advocated as are clarification of patient responses, impedance checks, assureing that the range of electrode configurations and stimulation parameters that patients and caregivers can implement are within safety margins, systematic clear and adaquete documentation, resetting counters and indicators, and encouraging the patient keeps the patient controller available at all times. Topics of troubleshooting are reviewed.
Discrete Neural Oscillators
Authors: Montgomery Erwin B.
Published: November 2017

The therapeutic mechanisms of action of DBS likely involve neural and neuronal oscillators. “Neuronal oscillators” describes periodic fluctuations of electrical potentials across the neuronal membrane, particularly in the soma, which is reflected in an action-potential-initiating segment. “Neural oscillators” describes closed loop (feedback) multi-neuronal polysynaptic circuits, on account of the propagations of action potentials through the circuit. Neural oscillators are the focus of this chapter. The features, properties and dyanmics introduced in Chapter 16 – Basic Oscillators are extended from continuous harmonic oscillators to discrete neural oscillators. While discrete oscillators received scant attention to date, systems of discrete oscillators have much richer set of dynamics that could provide better understanding of the pathophysiology and physiology of neural systems, such as the basal ganglia-thalamic-cortical system as well as greater insights into the therapeutic mechanisms of action underlying DBS.
Personal Knowledge and Study Participation
Authors: Dresser Rebecca
Published: November 2017

This chapter examines the educational value of becoming a research subject. Scientists in earlier times considered self-experimentation an essential component of their work. They thought that exposing themselves to untested interventions was the most ethical way to gauge the human response to those interventions. The practice was also educational, for it produced useful information that helped researchers plan subsequent human studies. Self-experimentation was eventually replaced by more sophisticated scientific methods and comprehensive ethical codes governing human research. But it is time to bring back the practice of self-experimentation, albeit in modified form. Serving as a study subject can be a valuable form of education for people who conduct and review proposals for human research.
The Everyday Ethics of Human Research
Authors: Dresser Rebecca
Published: November 2017

This chapter describes subjects’ views on their research experiences. Subjects have their own opinions about research ethics. For example, a study staff’s kind or rude behavior strongly influences whether subjects feel respected in the research process. Subjects also describe study burdens that researchers and other outsiders don’t always recognize. People deciding whether to allow a family member with dementia to participate in research tend to be more concerned about protecting their relative’s current welfare than about promoting his or her previous values. Findings like these show what people with personal research experience can contribute to the work of research ethics review committees, study teams designing and conducting research, and groups developing ethical and regulatory policies on specific research questions.
The Hidden World of Subjects
Authors: Dresser Rebecca
Published: November 2017

This chapter looks at subjects’ concealed misbehavior in research. When their personal interests conflict with the demands of participation, some subjects put their own interests first. They don’t follow study requirements and try to hide this fact from researchers. In rejecting the restrictions research imposes, subjects diminish the value of research results. They create risks to themselves and others; they also disregard ethical responsibilities to adhere to research agreements and tell the truth. At the same time, rule-breaking subjects expose ethical problems in the design and conduct of clinical trials. Features of the research environment create fertile ground for concealed rule-breaking. Intensified policing and guidance are two common strategies for reducing subject misbehavior, but collaborative reforms are more consistent with the partnership model of clinical research.
Embedded Ethics in Developing-Country Research
Authors: Dresser Rebecca
Published: November 2017

This chapter considers subject inclusion in multinational studies. Many studies are initiated and financed by wealthy countries but are conducted in low-income countries. Community engagement and participatory research have a long history in developing-country research. Over the years, there has been impressive progress in including experienced subjects and other community members in research activities and in integrating research staff into communities where research is being carried out. This progress is due in part to the contributions of social scientists examining and evaluating various ways to involve subjects and other community residents in research decisions. The practice of “embedded ethics” is an advance that should be applied in domestic research as well.
Procreative Liberty
Authors: de Melo-Martín Inmaculada
Published: November 2017

Proponents of reprogenetics usually use a right-based liberal approach as the framework to assess and defend these technologies. They claim that reproductive choice is a basic freedom and that interfering with individuals’ autonomous reproductive choices is legitimate only when such choices clearly and seriously harm others. This chapter shows that, although appeals to procreative freedom are persuasive regarding some aspects of reproduction, they fail to settle important questions about the permissibility of reprogenetics. It calls attention to the lack of agreement on the existence and nature of reproductive liberty. It then shows that even if one agreed that reproductive liberty entails the right to procreate, further argument is needed to show that such a right also involves a right to have a particular child. It also shows that proponents’ contention that no relevant harms can be proven to result from the use of reprogenetics is unpersuasive.
Enhancing the Assessment of Reprogenetic Technologies
Authors: de Melo-Martín Inmaculada
Published: November 2017

Mitochondrial replacement, a new technological development that allows the creation of an embryo with genetic material from three different people, two of whom are women, has been enthusiastically embraced by reprogenetic proponents. Unlike other reprogenetic technologies currently in use, mitochondrial transfer results in germline modifications. This chapter offers a more adequate assessment of reprogenetic technologies, one that attends to context, is gendered, and recognizes the value-laden nature of these technologies. It points out that even if one were to accept that these techniques have a reasonable safety profile—something for which current evidence is actually lacking—attention to the ends that these techniques will presumably help achieve, and to the values that they reinforce and oppose, calls for skepticism about their moral permissibility.
A Brief Overview of the Effect of War Injuries on Sexual Health and Intimacy
Authors: Ellis Kathryn
Published: November 2017

This chapter establishes definitions of sexual health and intimacy, provides insight into how they interact and affect successful relationships, and communicates the importance of addressing the sexual and intimacy needs of injured service members and their partners. Common deployment-related diagnoses, including post-traumatic stress disorder, traumatic brain injury, orthopedic injuries, spinal cord injuries, genital injuries, burns, and facial injuries, and their possible corresponding limitations are reviewed, along with how such limitations can result in sexual avoidance and intimacy avoidance, thus leading to more relationship issues and poor quality of life. The experience of partners, including perceptions about the dependence of the injured service member, is discussed as well.
Training Health Care Providers to Deal with Sexual Health and Intimacy Issues
Authors: Miletski Hani
Published: November 2017

This chapter outlines and describes the training for health care providers so that they can be more helpful to our wounded warriors who are dealing with sexual health and intimacy issues. Unfortunately, few medical and mental health care providers are trained in intimacy and sexuality matters, and many are not comfortable discussing these intimate issues at all. Therefore, the first step is to complete a Sexual Attitude Reassessment (SAR) seminar, if possible. In addition, training suggestions for knowledge building and skill development are described. These include the inviting the patient to talk, the PLISSIT model (Permission, Limited Information, Specific Suggestions, Intensive Therapy), taking a sexual history, and sex therapy.
Psychological Aspects of Infertility Post-Injury
Authors: Covington Laura S.
Published: November 2017

This chapter explores how service members with injuries that damage sexual and reproductive functioning may experience the psychosocial implications of impaired fertility. It addresses a general overview of infertility and then describes the experience within the military context. Infertility can be an invisible, secondary wound that is not felt until one considers procreation and that may last for many years. Further, infertility is an injury that affects not only the service member but also his or her partner. Many ethical considerations and barriers, including limited insurance coverage and accessibility for treatment, make it difficult to access technologies for reproduction. Fertility preservation and sperm harvesting should be considered as options by service members before deployment. While advances in technologies can help injured service members to procreate, the challenges and emotional fallout are significant and need to be addressed in treatment, counseling, and public policy.
Evolution of Sexual Trauma Treatment in the Military
Authors: Lande R. Gregory , Ghurani Sawsan , Burton Cara N. , Earley Kerrie
Published: November 2017

Military sexual trauma (MST) continues to be a widespread area of concern and has received much attention across the nation over the past decade. MST is a significant risk factor for developing post-traumatic stress disorder (PTSD). The military component of MST makes this trauma even more of a risk factor due to the military culture of developing strong emotional bonds of trust essential for combat operations. Due to the paucity of evidence based treatments for PTSD secondary to MST, many treatment facilities would treat PTSD secondary to MST and combat PTSD with the same therapies, however, this proved to be insufficient. The Psychiatry Continuity Service at Walter Reed National Military Medical Center recognized this gap in treatment and specifically designed an outpatient intensive day program to provide a comprehensive clinical interventions targeting MST.
Sources of Contaminants in the Home
Authors: Denninghoff James S. , vom Saal Frederick S.
Published: November 2017

Exposure to contaminants in the home and all indoor spaces can cause disease, including chronic inflammation, allergy, and asthma. Controlling dust, which can contain mold spores, insect parts, fecal material, pet dander, skin fragments, packaging materials, dust mites, volatile cleaning agents, and carpet fragments, is essential for clean indoor air. Dust is a vector for chemical toxins and organic and inorganic materials, which are sources of inflammation. The triggered immune response plays a central role in the pathogenesis of asthma, allergy, and sinusitis. Controlling humidity is necessary to minimize mold and the infiltration of dust mites and other insects in the home.
Interaction of Pharmaceuticals with Environmental Chemicals
Authors: Martino-Andrade Anderson J. , Swan Shanna H.
Published: November 2017

This chapter describes research on several commonly used analgesics that have been described as endocrine-disrupting chemicals, leading to concerns about possible interactions between therapeutic drugs and chemicals in the environment. Mild analgesics such as acetaminophen are widely used by pregnant women worldwide. In vitro, in vivo, and epidemiologic studies report that prenatal exposure to acetaminophen and other mild analgesics can cause hormonal disturbances resulting in gonadal development and male genital abnormalities, particularly cryptorchidism. These results suggest the potential for interaction between mild analgesics and environmental chemicals such as phthalates because they appear to disrupt similar hormonal signaling systems and cause common reproductive changes. Given the increased prevalence of prenatal exposure to phthalates and analgesics, these potential adverse effects should be taken into account when considering the risks and benefits of mild analgesic use during pregnancy.
Classic Toxicology vs. New Science
Authors: Vandenberg Laura N.
Published: November 2017

Endocrine-disrupting chemicals (EDCs) are compounds that interfere with hormone action. Many EDCs are agonists or antagonists of estrogen, androgen, or thyroid hormone receptors. EDCs are found in many consumer products and are detected at low doses in humans. Using traditional methods from toxicology and risk assessment, these compounds have often been considered benign based on the low exposure levels and few overt signs of toxicity. However, thousands of epidemiology studies have found associations between EDC exposures and disease outcomes, suggesting that the methods used to prioritize chemicals and identify safe levels of exposure have failed. This chapter discusses the unique properties of EDCs that defy traditional chemical safety expectations. The presumption that chemicals are safe until proved harmful has allowed humans to be exposed to hundreds of chemicals that may be unsafe, at least during sensitive periods of development. Recommendations are offered for revising toxicologic evaluations to protect public health.
A 50-Year-Old Male with Speech, Swallowing, and Behavioral Difficulties
Authors: Cohen Jeffrey A. , Mowchun Justin J. , Lawson Victoria H. , Robbins Nathaniel M.
Published: November 2017

Treatment issues are discussed in the setting of a very challenging patient with amyotrophic lateral sclerosis with frontotemporal dementia (FTD), including management of neurological symptoms and cognitive dysfunction. Features of FTD are discussed. It is now appreciated that FTD is more common than previously thought. FTD can occur before the onset of motor symptoms. An ALS multidisciplinary clinic is the best approach for the care of ALS patients. Ethical issues are analyzed in this case as well. The need for the discussion of end of life issues is important for the patient family and caregivers. The careful consideration of tracheostomy and ventilator use is important in light of pulmonary function. Pulmonary function testing and sleep studies are helpful in managing respiratory issues. Palliative care consultation can be very beneficial.
A 30-Year-Old Male Requiring Management of Progressive Weakness
Authors: Cohen Jeffrey A. , Mowchun Justin J. , Lawson Victoria H. , Robbins Nathaniel M.
Published: November 2017

Management of Guillain-Barré syndrome involves several factors. Pulmonary function tests are important to monitor. Telemetry and blood pressure must be monitored because of the significant risk of autonomic dysfunction. Intravenous immunoglobulin is the immunotherapy of choice for this disease, as it is less complicated to administer than plasma exchange. Supportive management issues to address include deep vein thrombosis prophylaxis, bowel/bladder care as ileus and urinary retention may be develop secondary to dysautonomia, physical/occupational/speech therapy consults, nutrition, and pain control. Gabapentin can also be helpful for GBS-related pain. This chapter discusses an approach to treatment that includes the role of respiratory and autonomic monitoring as well as immunotherapy considerations.
A 61-Year-Old Male with Severe Shoulder and Cervical Pain
Authors: Cohen Jeffrey A. , Mowchun Justin J. , Lawson Victoria H. , Robbins Nathaniel M.
Published: November 2017

Severe shoulder pain in the absence of a clear orthopedic cause may be due to acute brachial plexitis. Numbness and tingling in association with weakness and muscle atrophy that cannot be accounted for by a single nerve or nerve root distribution suggests the diagnosis. Additional clues suggesting brachial plexitis include intensity of shoulder pain and antecedent events such as illness, vaccination, injury, unusual physical activity or surgery. The approach to diagnosis of plexitis/plexopathy and appropriate evaluation for etiology are discussed. Management of this condition is conservative, relating to pain control and judicious use of mobilization and strengthening with physical therapy. Prognosis is generally good with recovery of strength occurring in weeks to months.
A 68-Year-Old Male with Progressive Numbness and Gait Difficulties
Authors: Cohen Jeffrey A. , Mowchun Justin J. , Lawson Victoria H. , Robbins Nathaniel M.
Published: November 2017

Paraproteinemic demyelinating peripheral neuropathies require specific diagnostic and management approaches. The clinical features as well as the type of monoclonal protein and possible associated antibodies are all important considerations in evaluation and management of these complex presentations. It is important to recognize anti-myelin associated glycoproteins positive peripheral neuropathy, which is associated with IgM gammopathy, and typically presents with a sensory ataxia. Hematologic disease may mimic chronic inflammatory demyelinating polyneuropathy. This chapter also describes the role of hematological evaluation for patients with peripheral neuropathy and a monoclonal gammopathy.
A 44-Year-Old Man with Bilateral Facial Droop
Authors: Cohen Jeffrey A. , Mowchun Justin J. , Lawson Victoria H. , Robbins Nathaniel M.
Published: November 2017

Facial neuropathy is most commonly seen as an idiopathic unilateral palsy known as Bell’s palsy. Generally, acute onset of typical lower motor neuron facial weakness that is not associated with other atypical or suspicious features, remains unilateral, and recovers completely requires no further workup. A recurrent or bilateral peripheral facial palsy makes an idiopathic cause less likely and prompts a more in-depth workup. The appropriate work-up of unilateral or bilateral facial palsy guided by the presence or absence of associated clinical findings is discussed. The major differentials for bilateral facial paresis include brainstem (especially pontine and prepontine) tumors, Lyme disease (especially in endemic areas), basal menigitides, Guillain-Barre syndrome, and sarcoidosis.
A 44-Year-Old Female with Buttock Pain
Authors: Cohen Jeffrey A. , Mowchun Justin J. , Lawson Victoria H. , Robbins Nathaniel M.
Published: November 2017

Sciatic neuropathy presents with buttock pain worsened by sitting on the affected side and associated with ankle and knee extension weakness. Electrodiagnostic evaluation will help to distinguish it from peroneal or tibial mononeuropathies, lumbosacral plexopathy, or lumbosacral radiculopathy. It can be difficult to distinguish from a peroneal mononeuropathy due to the preferential involvement of the peroneal division of the sciatic nerve. EMG study of the short head of the biceps femoris allows for distinction between these entities. Long-term outcome and prognosis studies are sparse although Preservation of distal lower-extremity strength may be a significant predictor earlier and/or better clinical recovery.
A 34-Year-Old Male with Possible Myopathic Process
Authors: Cohen Jeffrey A. , Mowchun Justin J. , Lawson Victoria H. , Robbins Nathaniel M.
Published: November 2017

Adult-onset spinal muscular atrophy (SMA type IV) presents in a manner similar to a myopathy. Normal CK and a neurogenic pattern of denervated changes on electrodiagnostic study suggest the actual diagnosis. The diagnosis of SMA is confirmed by the presence of a homozygous deletion or mutation of the SMN1 gene in most patients. Both the presence of SMN1 deletion/mutation and the effectiveness of rescue from a second copy of the gene, SMN2, determines the age at onset and severity of SMA. Differential includes other genetic conditions affecting motor neurons, postpolio syndrome, monomelic amyotrophy, and motor neuropathies/poly-radiculopathies. The management of SMA is predominantly supportive, but this can significantly impact quality of life.
A 39-Year-Old Man with Low Back Pain and Scapular Winging
Authors: Cohen Jeffrey A. , Mowchun Justin J. , Lawson Victoria H. , Robbins Nathaniel M.
Published: November 2017

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common muscular dystrophy, following Duchenne muscular dystrophy and myotonic dystrophy. The clinical secerity is extremely variable, with symptom onset anywhere from infancy to middle adulthood. The cardinal clinical features of facioscapulohumeral muscular dystrophy include facial weakness and scapular winging. Other important examination findings including scalloping of the trapezius, “Popeye” forearms, horizontal axillary folds, and a positive Beevor’s sign. It can rarely present as a pattern of weakness mimicking limb-girdle muscular dystrophy with approximately 20% of patients eventually requiring a wheelchair for ambulation. Creatine kinase is normal or mildly elevated. Genetic testing for the D4Z4 repeat contraction on chromosome 4q35 detects 95% of cases but may not reflect severity of the disease.
A 19-Year-Old Male with Stiffness and Weakness After Waking
Authors: Cohen Jeffrey A. , Mowchun Justin J. , Lawson Victoria H. , Robbins Nathaniel M.
Published: November 2017

The distinctive, but somewhat odd, development of intermittent “attacks” of weakness/stiffness define this disorder. Interview of the patient to determine the impact of diet (including timing, content and relationship of attack to fasting), activity, emotional stress, alcohol intake, cold exposure, time of day and physiologic perturbations (eg – electrolytes, infection, dehydration, etc) help to confirm and categorize the periodic paralysis. Periodic paralyses are most often associated with a genetic channelopathy. However, they can also occur as a result of a secondary causes including thyroid disturbance or distal renal tubular acidosis. The clinical picture, laboratory investigation, and treatment of this condition are presented.
An 80-Year-Old Myasthenia Gravis Patient with Worsening Weakness
Authors: Cohen Jeffrey A. , Mowchun Justin J. , Lawson Victoria H. , Robbins Nathaniel M.
Published: November 2017

In myasthenia gravis, weakness and respiratory insufficiency can occur quickly. It is important for the treating physician to recognize this and institute treatment rapidly. Increasing weakness of the neck may herald impending respiratory insufficiency. The single breath count is an easy way ti assess ventilatory function. Because of bulbar weakness and increasing secretions usually bi-level positive pressure airway pressure is used with extreme caution. Intubation with effective management if the airway is preferred. Differentiation of myasthenic crisis from cholinergic crisis is explained; although cholinergic crisis is relatively uncommon. Treatment modalities can include intravenous immunoglobulin, plasma exchange, and corticosteroids. Corticosteroids should be used with caution since they may exacerbate myasthenic symptoms. Treatment with a steroid sparing agent is discussed. A table is presented which lists signs and symptoms that can suggest the need for intubation.
Masquerade
Authors: Chong Ji Y. , Lerario Michael P.
Published: November 2017

The diagnosis of a stroke mimic is typically made after the acute setting when the window for acute treatment has closed. Patients with stroke mimics who are eligible for tPA may safely be treated with a minimal risk of intracranial hemorrhage.
Malignant Edema
Authors: Chong Ji Y. , Lerario Michael P.
Published: November 2017

Large middle cerebral artery (MCA) and cerebellar strokes can cause rapid neurological deterioration and death from edema, mass effect, and herniation. Hemicraniectomy in select patients with malignant MCA syndromes is life-saving, but patients are often left with significant disability. Younger patients may derive the most benefit from hemicraniectomy. Cerebellar strokes can also cause obstructive hydrocephalus, which may exacerbate herniation and brainstem compromise. Surgical decompression through suboccipital craniectomy relieves posterior fossa pressure and reduces mortality in these patients.
Unidentified Bright Objects
Authors: Chong Ji Y. , Lerario Michael P.
Published: November 2017

There are many modifiable risk factors for stroke. Screening for risk factors in the primary care setting and instituting early lifestyle modification or medical treatment of risk factors will lower the risk of incident stroke.
Small Vessel Disease
Authors: Chong Ji Y. , Lerario Michael P.
Published: November 2017

Lacunar strokes are strongly associated with hypertension. Long-term blood pressure management is important after lacunar stroke. Antiplatelet therapy should be instituted for secondary stroke prevention.
Obstructed Flow
Authors: Chong Ji Y. , Lerario Michael P.
Published: November 2017

Patients with symptomatic carotid stenosis benefit from revascularization. The risk of recurrent stroke is highest during the early period after a transient ischemic attack or stroke. Carotid endarterectomy and carotid stenting are options for treatment and should be considered within the first 2 weeks if feasible.
Aphasia and Atherosclerosis
Authors: Chong Ji Y. , Lerario Michael P.
Published: November 2017

High-grade intracranial atherosclerosis is associated with a high risk of recurrent stroke. Medical therapy with antiplatelet therapy and aggressive risk factor control is the preferred treatment regimen for stroke prevention in patients with intracranial atherosclerosis. Current stenting techniques are associated with high morbidity and mortality.
Investigating the Occult
Authors: Chong Ji Y. , Lerario Michael P.
Published: November 2017

Occult atrial fibrillation is more common than previously thought in patients with cryptogenic stroke, particularly in older cohorts. If stroke patients are suspected to have atrial fibrillation, intensive cardiac monitoring using implantable loop recorders or prolonged external monitors should be ordered and can result in higher rates of arrhythmia detection.
Young Adult with Headache and Blurred Vision
Authors: Chong Ji Y. , Lerario Michael P.
Published: November 2017

Traditional vascular risk factors such as hypertension, diabetes, and high cholesterol can contribute to stroke in young adults. In the absence of typical risk factors in a young patient, a more extensive evaluation is needed. Other, more unusual causes of stroke can include autoimmune, infectious, hematological, and toxic etiologies. Often, despite an exhaustive workup, the mechanism of stroke remains cryptogenic in younger patients.
Thunderclap Headache
Authors: Chong Ji Y. , Lerario Michael P.
Published: November 2017

Reversible cerebral vasoconstriction syndrome can cause thunderclap headache, subarachnoid hemorrhage, and stroke. The clinical presentation can be similar to aneurysmal subarachnoid hemorrhage and therefore requires rapid angiography. Angiographic findings of vasculopathy and resolution of clinical symptoms and imaging abnormalities support this diagnosis. This syndrome is most often incited following pregnancy or the ingestion of a vasoactive medication.
Numbness While on Anticoagulation
Authors: Chong Ji Y. , Lerario Michael P.
Published: November 2017

Hemorrhagic stroke is associated with high morbidity and mortality. A common cause of intracerebral hemorrhage (ICH) is hypertension. Patients with suspected ICH should be immediately evaluated with computed tomography (CT) scanning. If coagulopathic, correction of coagulopathy must be instituted rapidly. Hemorrhage due to hypertension usually occurs in subcortical locations. In patients with atrial fibrillation and ICH, a careful analysis of each individual’s risks and benefits must be performed prior to resuming anticoagulation for ischemic stroke prevention. Prevention involves aggressive blood pressure control.
Progressive Gait Dysfunction
Authors: Chong Ji Y. , Lerario Michael P.
Published: November 2017

Spinal vascular malformations are rare, with dural arteriovenous fistulas (AVFs) accounting for the majority of the pathology. Unlike spinal arteriovenous malformations, which cause abrupt neurological change as a result of hemorrhage, spinal dural AVFs tend to result in a progressive myelopathy through venous congestion and cord edema. If diagnosed and treated early with endovascular embolization or microsurgery, some deficits may be reversible.
Seizures, Sadness, and Spasticity
Authors: Chong Ji Y. , Lerario Michael P.
Published: November 2017

Due to the brain’s inherent neuroplasticity, stroke patients can make major functional improvements during the first 3–6 months post-injury. Aggressive physical, occupational, and speech therapies should be focused to address individual patient needs. Depression is very common post-stroke, and if left untreated, it may lead to worsened functional outcomes. The development of spasticity post-stroke can impair motor recovery and should be treated with physiotherapy, oral antispasmodics, or local botulinum toxin injections, depending on the severity.
Ménière Recognizes That Vertigo Can Originate from the Inner Ear
Authors: Baloh Robert W.
Published: November 2017

Prosper Ménière was the first clinician to conclude that vertigo can result from diseases of the inner ear. The symptom of vertigo originally fell under the rubric of apoplectiform cerebral congestion, a disorder thought to result from overfilling of blood vessels in the brain. Ménière noted that patients with vertigo and hearing loss associated with damage to the inner ear often have a benign course, and aggressive treatments such as bleeding can be more dangerous than the underlying disease. The first hint that the semicircular canals may be related to balance rather than hearing was provided by a Frenchman, Marie Jean Pierre Flourens. He systematically cut each semicircular canal in the pigeon and noted that the animal’s head and body tended to move in the plane of the damaged canal. The gyrations of the animals described by Flourens made Ménière think that vertigo in humans might be a similar phenomenon.
Ménière, a Man of Many Interests
Authors: Baloh Robert W.
Published: November 2017

Prosper Ménière was born in1799 in Angers, France. Ménière completed 3 years at the Preparatory School of Medicine at the University of Angers before moving to Paris in 1819 to complete his medical studies. He received his doctorate of medicine in 1828 and was appointed as an aide in the clinic of the famous surgeon Baron Dupuytren in the Hôtel-Dieu. The way that Ménière went about educating himself on the anatomy, physiology, and pathology of the ear after his appointment to head the Deaf-Mute Institute in 1838 provides insight to his analytic approach. In the years that he served as Director of the Deaf-Mute Institute, Ménière socialized with some of the most prominent members of mid-19th-century France. He was probably as well known a figure in society as he was as a physician. Ménière was a complex man with many different interests and many talents.
Breuer’s Experiments on the Semicircular Canals and Otolith Organs
Authors: Baloh Robert W.
Published: November 2017

After his groundbreaking work in the mid-1860s, Josef Breuer continued to perform experiments on the inner ear balance receptors in animals. He studied the macules of fish, reptiles, and birds and noted that all these creatures had three macules arranged in the planes of the semicircular canals, perpendicular to one another. By contrast, mammals had only two macules located in the utricle (horizontal plane) and saccule (vertical plane), again perpendicular to each other. He developed the concept of “slip” to describe the movement of the otoconial membrane over the underlying sensory epithelium that occurred with linear displacement or gravity. He developed a mathematical model to hypothesize that in humans there was only one combination of responses from the two macules on each side for a single head position in space.
Breuer’s Contributions to Psychiatry and Philosophy
Authors: Baloh Robert W.
Published: November 2017

Josef Breuer was a practicing physician who saw many patients with psychiatric symptoms. He was a scientist and philosopher, but at his core he was a physician. His foray into the field of psychiatry can be directly traced to his patients, particularly a girl who became ill while she was nursing her sick father. Breuer and Freud called the girl Anna O. in their book on hysteria, but later it was revealed that her name was Bertha Pappenheim. Breuer first told Freud about Pappenheim in November 1882 approximately 5 months after he stopped treating her. It would be more than a decade, however, before they published her case history. Breuer and Freud collaborated on numerous clinical cases, but Breuer did not write any further on psychoanalysis. Breuer did maintain an active interest in the function of the inner ear until his death in 1925.
Schuknecht’s Temporal Bone Bank in Boston
Authors: Baloh Robert W.
Published: November 2017

When Harold Schuknecht arrived at Harvard in 1961, he immediately set up a temporal bone laboratory and began collecting specimens. Schuknecht obtained two specimens from patients with a typical clinical picture of benign paroxysmal positional vertigo (BPPV). In these specimens, Schuknecht identified a prominent granular basophilic staining mass attached to the cupula of the left posterior semicircular canal. Based on his findings, Schuknecht coined the term “cupulolithiasis” (“stones on the cupula”) to explain the clinical syndrome of BPPV. He assumed that substances having a specific gravity greater than endolymph and thus subject to movement with changes in the direction of gravitational force come into contact with the cupula of the posterior semicircular canal. With the head in the erect position, the posterior canal ampulla is located inferiorly, whereas in the provocative test position (supine, head hanging, ear down) the posterior canal assumes a superior position.
Smoothing out the Ups and Downs
Authors: Walsh Richard A.
Published: November 2017

The progressive loss of nigrostriatal dopaminergic neurons with advancing disease exposes the trough between every dose of levodopa in Parkinson’s disease. This is due to the combination of a loss of native dopamine production to fill in this interdose interval and a reduction in dopaminergic terminals to take up and release dopamine long beyond its short plasma half-life. The clinical result is wearing off—an awareness in patients of returning symptomatology while waiting for their next dose. Where consistent and impacting negatively on function on any level, there are a number of initial oral approaches to smooth out dopaminergic stimulation before more invasive advanced therapeutic options need to be considered.
“He Wants It All the Time, Doctor”
Authors: de Bie Robertus M. A.
Published: November 2017

Impulse-control disorders are an increasingly recognized complication of dopaminergic therapy in Parkinson’s disease, being present in approximately 15% of patients treated with dopamine agonists but also observed in patients treated with levodopa (referred to as “dopamine dysregulation syndrome”). Impulse-control disorders include pathological gambling, hypersexuality, compulsive shopping, and compulsive eating. Factors associated with a higher risk for impulse-control disorders are a young age at disease onset, a history of addictive behavior before the disease started, a family history of addiction such as alcoholism, and being male. It is undoubtedly true that current estimates are conservative due to embarrassment or shame preventing patients from disclosing behavioral change to their doctors. All patients must be questioned about impulse-control disorders at every visit, and where possible a collateral should be obtained from a family member or carer.