Showing papers in "Seminars in Neurology in 2018"

Global Burden of Stroke.

Abstract: Stroke is the second leading cause of death and a major cause of disability worldwide. Its incidence is increasing because the population ages. In addition, more young people are affected by stroke in low- and middle-income countries. Ischemic stroke is more frequent but hemorrhagic stroke is responsible for more deaths and disability-adjusted life-years lost. Incidence and mortality of stroke differ between countries, geographical regions, and ethnic groups. In high-income countries mainly, improvements in prevention, acute treatment, and neurorehabilitation have led to a substantial decrease in the burden of stroke over the past 30 years. This article reviews the epidemiological and clinical data concerning stroke incidence and burden around the globe.

The Global Burden of Headache

Abstract: At the turn of the century, most of the world's population lived in regions where the prevalence of headache was unknown and its impact poorly understood. Lifting The Burden (LTB), a nonprofit organization in official relations with the World Health Organization, established the Global Campaign against Headache, with the ultimate purpose of reducing the burden of headache worldwide. First, the scope and scale of this burden had to be known. LTB embarked upon a program of population-based studies in countries in all world regions in order to achieve its aim. Its studies have demonstrated a high prevalence of headache disorders, including migraine, tension-type headache, and medication-overuse headache, and their associations with impaired quality of life, substantial lost productivity, and high economic costs in every country surveyed. Informed by these, the Global Burden of Disease study ranks headache disorders as the second leading cause of years lived with disability worldwide; migraine alone is third among people aged 15 to 49 years. With interventions urgently needed to reduce these burdens throughout the world, we review the epidemiological studies conducted by LTB, examine proposed interventions to improve provision of headache care including a three-tier system of structured headache services, and consider the challenges still remaining in providing effective, efficient, and equitable headache care especially in low-income countries.

Origin of Gliomas

Abstract: Malignant glioma is a common type of brain tumor that remains largely incurable. Although a definitive cell of origin of gliomas remains elusive, numerous population studies, sequencing efforts, and genetically engineered mouse models have contributed to our understanding of the early events that may lead to gliomagenesis. Herein we summarize our current knowledge on the population epidemiology of gliomas, heritable genetic risk factors, the somatic events that contribute to tumor evolution, and mouse models that have shed light on the glioma cell of origin. Future studies will increase our understanding of the sequence of early events within susceptible cells and their niche that trigger the path to malignant transformation. Such knowledge will allow us to design more effective treatment options to control tumor growth or screening methods for early detection.

Neurofibromatosis and Schwannomatosis.

Abstract: Neurofibromatosis 1, neurofibromatosis 2, and schwannomatosis are a group of related classically inherited but often times sporadic tumor suppressor syndromes. Neuro-oncologists should recognize these syndromes, initiate necessary tests in patients with a clinical suspicion, and support genetic counseling of patients and families. In this review, clinical presentation, diagnostic criteria, day-to-day management including supportive care as well as updates on genetics, and experimental treatment strategies are discussed.

The Global Neurological Burden of Tuberculosis.

Abstract: Central nervous system (CNS) involvement of tuberculosis (TB) is the most severe manifestation of TB and accounts for approximately 5 to 10% of all extrapulmonary TB (EPTB) cases and approximately 1% of all TB cases. TB meningitis (TBM) is the most common form of CNS TB, though other forms occur, often in conjunction with TBM, including intracranial tuberculomas, tuberculous brain abscesses, and spinal tubercular arachnoiditis. CNS TB often presents with nonspecific clinical features that mimic symptoms of other neurological conditions, often making diagnosis difficult. Defining neuroimaging characteristics of TBM include thick basal meningeal enhancement, hydrocephalus, and parenchymal infarctions most commonly involving the basal ganglia and internal capsule. Traditional cerebrospinal fluid sample analysis frequently requires lengthy times-to-result and have low sensitivity. Given the pitfalls of conventional CNS TB diagnostic methods, various molecular-based methods, including immunoassays and polymerase chain reaction (PCR)-based assays have emerged as alternative diagnostic tools due to their rapidity, sensitivity, and specificity. Expert panels on TBM have recently emphasized the need for standard research procedures with updated case definitions and standardized study methods, which will hopefully pave the way for more robust multicenter international studies. In this article, we review the epidemiology, diagnosis, molecular factors associated with disease presentation and outcome, and treatment of CNS TB.

Meningiomas: Overview and New Directions in Therapy

Abstract: The majority of meningiomas, the most common primary brain tumor, are considered to be benign, and characteristic magnetic resonance imaging features allow a preliminary diagnosis. Meningiomas can be classified in the World Health Organization system as grade I, II, or III, depending on various histological features. In many cases, observation is the preferred management option, although this means the absence of a histological diagnosis. If necessary, standard therapy consists of surgery with or without adjuvant radiation, depending on the tumor grade and the degree of resection. To date, systemic therapies are not included in the standard of care. The level of evidence for treatment recommendations is low, and effective treatment regimens, especially for surgery-refractory and radiation-refractory meningiomas, are still very limited. Recent studies have broadened our knowledge of the genetics and pathogenesis of meningiomas and will lead to new therapeutic options. This review summarizes the epidemiology, pathogenesis and genetics, classification, and diagnosis of meningiomas, as well as management principles, including promising new avenues of therapy.

Grading of Diffuse Astrocytic Gliomas: A Review of Studies Before and After the Advent of IDH Testing.

Abstract: Estimating the malignancy level of tumors is key to management, and has been part of oncology practice for the past ∼100 years. A central aspect of assessing malignancy level is based on histological "grading"-a process in which a pathologist evaluates microscopic features of a tumor and interprets those findings in light of large prognostic studies. For the diffuse astrocytic gliomas, there have been many such studies over the past century and these have proven useful in estimating prognosis for patients. With the advent of molecular genetics, molecular diagnostic testing has been added to histological evaluation in the armamentarium of the pathologist, and the recent World Health Organization (WHO) Classification of Tumors of the Central Nervous System encourages testing for isocitrate dehydrogenase (IDH) gene status in the classification of diffuse astrocytic gliomas. The present review catalogues a large series of diffuse astrocytic glioma grading studies over the past few decades, and compares the prognostic value of such grading schema before and after the emergence of IDH testing. The review concludes that novel approaches to diffuse astrocytic tumor grading are required in the era of IDH testing.

Global Neurology: Navigating Career Possibilities

Abstract: Neurology has not typically been associated with international relief work; however, with the growth of chronic cardiovascular disease and stroke associated with unhealthy eating and sedentary ways, the appearance of “new” neurologic diseases, such as the Zika and West Nile viruses, and the high numbers of seizure disorders resulting from neuroinfectious diseases, more opportunities are arising for international and globally oriented neurologists. Multiple opportunities exist for developing a global clinician–educator career pathway, including private institutions, nongovernmental organizations, government-funded opportunities such as Medical Education Partnership Initiative, Fogarty and Fulbright Scholarships, and the American Academy of Neurology's Global Health Section. Furthermore, increasing research capacity in developing countries and increased funding opportunities for global health research have led to new opportunities for neurologists to establish global health research careers. These opportunities could not have come at a better time, as many faculty members have noted a particularly strong interest in global neurology from medical students and residents. Career categories and opportunities for neurologists desiring to work globally are discussed along with the emerging “global neurologist” academic pathway.

New Directions in the Treatment of Glioblastoma.

Abstract: Glioblastoma (GBM) is the most common primary malignant tumor of the central nervous system. The current standard of care for GBM is maximal resection followed by postoperative radiation with concomitant and adjuvant temozolomide. Despite this multimodality treatment, the median survival for GBM remains marginally better than 1 year. In the past decade, genome-wide analyses have uncovered new molecular features of GBM that have refined its classification and provided new insights into the molecular basis for GBM pathogenesis. Here, we review these molecular features and discuss major clinical trials that have recently defined the field. We describe genetic alterations in isocitrate dehydrogenase, ATRX, the telomerase promoter, and histone H3 variants that promote GBM tumorigenesis and have altered GBM categorization. We also discuss intratumoral genetic heterogeneity as one explanation for therapeutic failures and explain how ultra-long extensions of glioma cells, called tumor microtubes, mediate therapeutic resistance. These findings provide new insights into GBM biology and offer hope for the development of next-generation therapies.

Planning Education for Long-Term Retention: The Cognitive Science and Implementation of Retrieval Practice.

Abstract: Educational systems are rarely designed for long-term retention of information. Strong evidence has emerged from cognitive psychology and applied education studies that repeated retrieval of information significantly improves retention compared to repeated studying. This effect likely emerges from the processes of memory consolidation and reconsolidation. Consolidation and reconsolidation are the means by which memories are organized into associational networks or schemas that are created and recreated as memories are formed and recalled. As educators implement retrieval practice, they should consider how various test formats lead to different degrees of schema activation. Repeated acts of retrieval provide opportunities for schemas to be updated and strengthened. Spacing of retrieval allows more consolidated schemas to be reactivated. Feedback provides metacognitive monitoring to ensure retrieval accuracy and can lead to shifts from ineffective to effective retrieval strategies. By using the principles of retrieval practice, educators can improve the likelihood that learners will retain information for longer periods of time.

Neuropalliative Care: A Practical Guide for the Neurologist

Abstract: Neuropalliative care is a new and growing field within neurology that focuses on improving the quality of life of patients with serious neurologic illnesses. While specialty-level palliative care training is available to interested neurologists, all neurologists can strive to provide primary palliative care for their patients. In this review, we will describe the scope of neuropalliative care, define patient populations who may benefit from palliative care, and explore the communication and symptom management skills essential to palliative care delivery.

Pathogenic Mechanisms and Clinical Correlations in Autoimmune Myasthenic Syndromes.

Abstract: Autoimmune myasthenic syndromes are antibody-mediated disorders of the neuromuscular junction. Common antigenic targets are the acetylcholine receptor or muscle specific kinase (MuSK) in myasthenia gravis (MG) and the voltage-gated calcium channel in Lambert-Eaton myasthenic syndrome. There is evidence that antibodies directed against other antigens such as low-density lipoprotein receptor-related protein 4 (LRP4) are also involved in MG. The mechanisms by which various antibodies exert their pathogenic effect depend on the IgG subclass and also the epitope location on the antigens. These mechanisms are partly heterogeneous and include antigen degradation, complement activation, direct functional blocking, or disruption of protein-protein interactions. The neuromuscular junction is characterized by a structural and functional plasticity that is able to compensate for some of the neuromuscular junction defects. Here, we discuss the underlying pathogenic mechanisms of the different autoantibodies and correlate them with phenotypic features. The understanding of these elements should help guide the clinical management of patients with autoimmune myasthenic syndromes.

Emerging Viral Infections and Their Impact on the Global Burden of Neurological Disease.

Abstract: Emerging viral infections of the nervous system represent a major global public health concern in the 21st century. They are caused primarily by RNA viruses and are mostly associated with acute or subacute encephalitis. The spectrum of associated central or peripheral nervous system disorders is broad, and results either from a direct viral effect or due to the host immune responses against the infection. Emerging viral infections impose substantial neurological morbidity and mortality, particularly in low- and middle-income regions. In the past five decades, vector-borne viruses primarily transmitted by arthropods, or arboviruses, have been responsible for epidemics with a high burden of neurological disease, like the 2015–2016 Zika virus epidemic in the Americas. Viruses that have become neurovirulent for humans after geographical expansion include West Nile, Dengue, and Zika viruses. Factors such as animal migration, disruption of ecological niches, and cross-species contact have caused old viruses to reappear and cause neurological disease, as is the case of Ebola virus. In addition to these biological challenges, current preventive strategies, vaccination, and diagnostic and therapeutic approaches remain limited. We review the clinical-virological features and global impact of the most relevant emerging viral infections of the nervous system as they are projected over the 21st century.

Migraine and Tension-Type Headache.

Abstract: Migraine and tension-type headache (TTH) are common primary disorders that carry significant morbidity and socioeconomic effect. In this article, we will review the epidemiology, presentation, and diagnosis of these disorders. First-line acute treatment for migraine consists of analgesics, triptans, and antiemetics, while nonsteroidal anti-inflammatory drugs are the mainstay treatment for TTH. Patients with frequent or chronic headaches warrant prophylactic therapy. For migraine, various classes of preventives can be used (β-blockers, tricyclics, antiepileptics, botulinum toxin), with the choice of therapy tailored to the patient's risk factors and symptoms. For TTH, tricyclics have the most evidence as prophylactic therapy. A new class of medication, monoclonal antibodies to calcitonin gene receptor peptide or its receptor, became available in 2018, and is the first class of medication specifically designed to treat migraine. In addition to pharmacotherapy, we will also review nonpharmacologic interventions as well as neuromodulation for migraine.

Radicular Pain Syndromes: Cervical, Lumbar, and Spinal Stenosis.

Abstract: Back pain is a top primary and urgent care complaint; radicular pain can be caused by herniation of the nucleus pulposus (intervertebral disc), spinal stenosis, or degenerative changes to the vertebrae. The focus of this clinical review will be the clinical approach and treatment of lumbar radicular pain, cervical radicular pain, and spinal stenosis. Usually localized through neurological history, exam, and imaging, specific signs and symptoms for lumbar radicular, spinal stenosis, and cervical radicular pain can help determine etiology. Once radicular back pain has been diagnosed, a multitude of treatment options are available from rest and physical therapy to medications, epidurals, and surgery. The most common and accepted are reviewed. With accurate diagnosis, safe and effective pain management can be employed to shorten radicular episodes and manage recurrent or chronic radicular syndromes. Using a step-wise approach from diagnosis to conservative therapy to potential surgery, radicular pain syndromes can improve or resolve, and patients may achieve a better functional status and quality of life.

Managing Neurophobia: How Can We Meet the Current and Future Needs of Our Students?

Abstract: Neurophobia was defined more than two decades ago as a "fear of neural sciences and clinical neurology" among medical students. Despite recognition of the ailment and research into underlying causes, medical students and neurological educators continue to struggle with neurophobia today. At our institution, we have been successful at mitigating neurophobia. Here, we define the underlying drivers of neurophobia, based on the relevant literature. We also describe our strategies for battling neurophobia in the preclinical and clinical years by (1) establishing a continuum of neurological education; (2) incorporating active and observed learning throughout neurological education; and (3) enhancing socialization into neurology. Finally, we consider the future of neurological education, describe strategies for educators to mitigate neurophobia, and propose a call to action to further understand neurophobia. Neurophobia is not inevitable; effective curricula and dedicated faculty can engage students and ensure students better understand and enjoy their neurological education.

Concepts for Immunotherapies in Gliomas.

Abstract: Strategies to empower the immune system to successfully attack cancers, including vaccination approaches, adaptive T cell therapies, and immune checkpoint modulators, have recently achieved remarkable success across a spectrum of cancer indications. Nonetheless, with rare exception, only a minority of patients with a given type of cancer respond to an immunotherapeutic when administered as single-agent therapy. Although under extensive laboratory and clinical investigation, the role of these approaches for glioma patients remains to be determined. While the central nervous system (CNS) is no longer regarded as an immunoprivileged sanctuary, nuances regarding immune responses in the CNS may impact on the activity of immunotherapy treatments of brain tumor patients. Furthermore, many common CNS tumors such as World Health Organization grade III and IV (high grade) gliomas utilize myriad, nonoverlapping strategies to dampen or extinguish antitumor immune responses. For these reasons, critical research efforts are focused on identifying biomarkers that predict patients with a heightened likelihood of therapeutic benefit as well as evaluating rationally designed combinatorial immunotherapy approaches with potentially complementary mechanisms of immune-activation for brain cancer patients.

An Overview of Autoimmune and Paraneoplastic Encephalitides

Abstract: The understanding of the manifestations, mechanisms, and management of autoimmune encephalitis has expanded dramatically in recent decades. Immune-mediated encephalitides are comparable in incidence and prevalence to infectious etiologies, and are associated with significant morbidity, especially when there is a delay in recognition and treatment. As such, clinicians from many specialties must develop a functional understanding of these disorders. Herein we provide an overview of the autoimmune and paraneoplastic encephalitides, including those associated with either intracellular or cell surface/synaptic neuronal autoantibodies. After briefly reviewing the current understanding of the pathobiology of autoimmune encephalitis, we combine a neuroanatomical approach with specific antibody syndromes to provide the reader with a clinically relevant review of these disorders. The clinical manifestations, diagnosis, and management of autoimmune encephalitis are reviewed, with an emphasis on clinical relevance. We also introduce updates in the field, including autoimmune encephalitis associated with novel cancer immunotherapies, infectious triggers of autoimmune encephalitis, and autoimmune encephalitis with demyelinating overlap syndromes.

Diagnostic and Therapeutic Approach to Autoimmune Neurologic Disorders

Abstract: The field of autoimmune neurology is evolving rapidly. The discovery of autoantibodies that target neural antigens has expanded swiftly in the last decade. Recognition of the clinical syndromes associated with autoimmune neurologic disorders, and our understanding of the pathophysiology, has progressed significantly. Radiographic, electrophysiological, and laboratory testing (particularly neural autoantibody testing) are fundamental in the diagnosis of autoimmune neurological disorders and in the exclusion of mimics. Furthermore, investigations may serve as a baseline from which objective assessment of improvement or detection of relapse can be made. These disorders can be associated with underlying neoplasms, and screening for malignancy is an essential component of the investigations. Early diagnosis and prompt initiation of immunotherapy can improve neurologic function. The use of immunotherapy, however, can be associated with diverse side effects, and careful monitoring is crucial to prevent complications. Herein the authors address the diagnostic and treatment approach of autoimmune neurologic disorders, with particular focus on antibody-mediated neurologic autoimmunity.

Radiomics, Metabolic, and Molecular MRI for Brain Tumors

Abstract: Magnetic resonance imaging plays a key role in diagnosis and treatment monitoring of brain tumors. Novel imaging techniques that specifically interrogate aspects of underlying tumor biology and biochemical pathways have great potential in neuro-oncology. This review focuses on the emerging role of 2-hydroxyglutarate-targeted magnetic resonance spectroscopy, as well as radiomics and radiogenomics in establishing diagnosis for isocitrate dehydrogenase mutant gliomas, and for monitoring treatment response and predicting prognosis of this group of brain tumor patients.

Understanding Refugees' Health

Abstract: According to the United Nations Refugee Agency (UNHCR), 65.6 million people have been forcibly displaced worldwide. Several factors have a major influence on asylum seekers' health; so, their health profile is markedly different from that of the population in the country of asylum. The aim of this study is to review the major issues physicians need to be aware of when treating asylum seekers, with a special focus on the neurological problems of asylum seekers and refugees. The major impact factors on refugees' health are linked to experiences and exposure (1) in the country of origin, (2) in refugee camps and en route to Europe, and (3) in the process of immigration into the host country and living in European asylum centers. Refugees' health is also affected by psychological problems and by infectious diseases. Additionally, chronic diseases resulting in polymorbidity, cancer, and neurological diseases are easy to overlook and demand special attention. Neurological injuries/diseases may be traumatic (e.g., spinal cord injuries), posttraumatic (e.g., chronic pain syndromes), the result of cerebral infections, or the consequences of starvation (e.g., epilepsy, ataxia, and paraesthesia). The main challenges for physicians are lack of awareness of the asylum seekers' specific health care problems, language and intercultural communication problems, as well as access and integration of asylum seekers into the health care system. The health issues of asylum seekers are manifold and challenging to physicians. Awareness of these conditions is mandatory to ensure good clinical practice for this patient population, which has a huge burden in chronic, infectious, mental, and neurological diseases.

The Future of the Lecture in Neurology Education.

Abstract: The lecture has been a core pedagogical method since the early days of formal medical education. Although approaches to formal lectures have evolved over the years, there has been ongoing debate about the role that lectures should play in modern medical education. Arguably, traditional lectures do not align well with modern learning theory, and do not take full advantage of our current knowledge of how people learn. In many modern medical curricula, lectures have been replaced by self-study activities, including video-based lectures, computer-based learning modules, and other self-directed learning. We argue that scheduled "together time" is still important, particularly in neurology education, where there is a strong emphasis on clinical reasoning. We outline alternative teaching methods that effectively use this time, including the flipped classroom, just-in-time teaching, problem-based learning, and team-based learning. We discuss ways in which these approaches may be particularly conducive to components of neurology education.

Autoimmune and Paraneoplastic Myelopathies.

Abstract: Prompt recognition of an inflammatory myelopathy is critical, as a specific diagnosis and management plan allows for optimal patient outcomes. Many treatment options are now available for autoimmune and paraneoplastic myelopathies, but specific management strategies and expected prognosis vary widely depending on the underlying etiology. An understanding of the relevant clinical details, imaging findings, and other diagnostic information that can help achieve a specific myelopathy diagnosis and treatment plan is essential for all neurologists, given the variety of contexts in which myelopathies are encountered. We provide an outline of the diagnostic evaluation and treatment of various inflammatory myelopathies seen in autoimmune and paraneoplastic diseases, including multiple sclerosis, aquaporin-4 immunoglobulin G (IgG) seropositive neuromyelitis optica spectrum disorder, sarcoidosis, myelin oligodendrocyte glycoprotein IgG associated disease, and other rare inflammatory myelopathies; we also highlight common mimickers of inflammatory myelopathies.

Global Health: Epilepsy.

Abstract: Epilepsy is a frequently misunderstood and highly stigmatized condition. Major treatment gaps exist across the world, most so in areas of financial constraint. Classification permits the best approaches to treatment and to ascertaining prognosis. The International League Against Epilepsy's new classification system emphasizes clinical aspects and utilizes all available resources to determine whether it is a focal or generalized epilepsy. The most important tools are a careful history, clinical examination, electroencephalography, and appropriate neuroimaging. Inadequate, delayed, and incomplete evaluation may lead to misdiagnosis and costly mismanagement. Treatment is generally pharmacological, with approximately 20 to 30% of patients eventually proving refractory to medications and thus becoming potential surgical candidates. The type of epilepsy, age, gender, comorbidities, drug interactions, and drug cost are important factors in choosing an antiepileptic drug (AED). The teratogenic potential of some AEDs, weight gain, and menstrual hormone–related issues are important considerations in women. The impact of AEDs on bone health is critical in all age groups, particularly in the elderly. Psychiatric problems, mostly depression and anxiety, can have a great impact on seizure control and overall quality of life. Finally, effective partnerships and collaborations can bring resources, both human and financial, to regions that would otherwise find it impossible to effect change on their own.

Gliomas in Children.

Abstract: Gliomas are the most common primary central nervous system (CNS) neoplasms in children and adolescents and are thought to arise from their glial progenitors or stem cells. Although the exact cells of origin for most pediatric gliomas remain to be identified, our current understanding is that specific cell populations during CNS development are susceptible to particular oncogenic events during certain time windows and thus give rise to pediatric gliomas with distinct histological, molecular, and clinical features. These may be roughly segregated into low-grade gliomas (WHO grades I or II; including most mixed glial-neuronal tumors) and high-grade gliomas (WHO grades III or IV) according to their clinical course when untreated, even though this is not yet entirely clear for some of the recently emerging groups. The genetic and epigenetic characterization of pediatric gliomas across ages and histologies has facilitated the delineation of biologically relevant subgroups and have revealed potentially targetable alterations in some of them. This review outlines diagnostic features and molecular alterations in pediatric low- and high-grade gliomas and how the latter might be exploited with future targeted therapeutic strategies.

Autoimmune Epilepsy: The Evolving Science of Neural Autoimmunity and Its Impact on Epilepsy Management.

Abstract: Autoimmune epilepsy is increasingly recognized as a distinct clinical entity, driven in large part by the recent discovery of neural autoantibodies in patients with isolated or predominant epilepsy presentations Detection of neural autoantibodies in high-risk epilepsy patients supports an immune-mediated cause of seizures and, if applicable, directs the search for an underlying cancer when the paraneoplastic association of the associated antibody is compelling Early diagnosis of autoimmune epilepsy is crucial, as prompt initiation of immunosuppressive treatment increases the likelihood of achieving either seizure freedom or a substantial reduction in seizure frequency A practical clinical approach that incorporates risk scores to guide patient selection on the basis of clinical features, neural autoantibodies, and a treatment trial of immunotherapy is suggested Elucidating an immunological basis of epilepsy provides neurologists with wider treatment options (incorporating immune-suppressive treatment), in addition to standard antiepileptic drugs, which often improves patient outcomes

The "Growing" Reality of the Neurological Complications of Global "Stem Cell Tourism".

Abstract: “Stem cell tourism” is defined as the unethical practice of offering unproven cellular preparations to patients suffering from various medical conditions. This phenomenon is rising in the field of neurology as patients are requesting information and opportunities for treatment with stem cells for incurable conditions such as multiple sclerosis and amyotrophic lateral sclerosis, despite their clinical research and experimental designation. Here, we review the recent trends in “stem cell tourism” in both the United States and abroad, and discuss the recent reports of neurological complications from these activities. Finally, we frame critical questions for the field of neurology regarding training in the ethical, legal, and societal issues of the global “stem cell tourism,” as well as suggest strategies to alleviate this problem. Although there are ongoing legitimate clinical trials with stem cells for neurological diseases, procedures offered by “stem cell clinics” cannot be defined as clinical research. They lack the experimental and state-of-the-art framework defined by peers and the FDA that focus on human research that safeguard the protection of human subjects against economical exploitation, unwanted side effects, and futility of unproven procedures. “Stem cell tourism” ultimately exploits therapeutic hope of patients and families with incurable neurological diseases and can put in danger the legitimacy of stem cell research as a whole. We posit that an improvement in education, regulation, legislation, and involvement of authorities in global health in neurology and neurosurgery is required.

Contentious Ethical and Legal Aspects of Determination of Brain Death.

Abstract: Although the concept of death by neurologic criteria is accepted throughout much of the world and death can legally be determined by neurologic criteria throughout the United States, the process is fraught with contentious ethical and legal controversies. I explore historic and contemporary ethical and legal disputes about determination of death by neurologic criteria including the need for consent from patients' surrogates prior to determination of death, the role of religion in determination of death, management of objections to determination of death by neurologic criteria, the approach to patients who are dead by neurologic criteria but are pregnant, and gamete retrieval after determination of death.

Imaging Criteria in Neuro-oncology.

Abstract: The identification of more effective therapies for brain tumors has been limited in part by the lack of reliable criteria for determining response and progression. Since its introduction in 1990, the MacDonald criteria have been used in neuro-oncology clinical trials to determine response, but they fail to address issues such as pseudoprogression, pseudoresponse, and nonenhancing tumor progression that have arisen with more recent therapies. The Response Assessment in Neuro-Oncology (RANO) working group, a multidisciplinary international group consisting of neuro-oncologists, medical oncologists, neuroradiologists, neurosurgeons, radiation oncologists, and neuropsychologists, was formed to improve response assessment and clinical trial endpoints in neuro-oncology. Although it was initially focused on response assessment for gliomas, the scope of the RANO group has been broadened to include brain metastases, leptomeningeal metastases, spine tumors, pediatric brain tumors, and meningiomas. In addition, subgroups have focused on response assessment during immunotherapy and use of positron emission tomography, as well as determination of neurologic function, clinical outcomes assessment, and seizures. The RANO criteria are currently a collective work in progress, and refinements will be needed in the future based on data from clinical trials and improved imaging techniques.

Headache in Pregnancy, the Puerperium, and menopause.

Abstract: Headache is a neurologic disorder that displays gender dichotomy. It is well established that there is a strong link between migraine headache and sex hormones, specifically estrogen, which influences the severity of migraines during the menstrual cycle, pregnancy, and menopause. Furthermore, the epidemiology of headaches during pregnancy and the postpartum period is very distinct from that in males or nonpregnant females, in part due to the hemodynamic and hematologic changes that occur during pregnancy. These changes put women at higher risk for cerebral venous thrombosis, hemorrhagic stroke, and hypertensive disorders of pregnancy like preeclampsia, eclampsia, posterior reversible encephalopathy syndrome, and reversible cerebral vasoconstriction syndrome. Headache in pregnancy and the puerperium can be a cause of heightened anxiety in most women, who are concerned not only about the effect of the headache itself on the pregnancy but also about the effect of the treatment options on the pregnancy and the fetus. In this review, we discuss the latest literature on type and distribution of headaches during pregnancy and the postpartum period, and provide a digestible overview of the safety profile of commonly used abortive and prophylactic medications. We also discuss important considerations when treating migraine during menopause.