Biomedical publishing is an integral part of medicine—both to those who produce it and those who consume it to improve the care of their patients. Non-medical writing by surgeons usually takes the form of creative non-fiction, generally reflective essays on moving and emotionally charged situations such as working in the trenches in war-time or in natural disasters, or dealing with individual patients. Such writing is both creative and cathartic for neurosurgeons, and can help educate patients thus improving the doctor-patient relationship. The purpose of this article is to encourage fellow neurosurgeons to pursue this enjoyable and valuable endeavour, to utter a call to arms so to speak.

A great deal of progress has been made in the management of Alzheimer's disease and other dementias over the past 25 years. Much remains to be achieved, however. This article discusses some of the issues surrounding study design. In the absence of an accepted biological marker of progression, it is unlikely that a novel study design, such as randomized start or withdrawal, in itself could provide convincing evidence of disease modification. Biological markers will also be crucial in the development of therapies aimed at specific processes, and of immunotherapies.

The safety and efficacy of current symptomatic drugs for AD was established using parallel groups taking different doses of active drugs vs placebo over three to twelve months, whereas drugs with potential stabilizing/disease modifying effects are being tested by adding new compounds or placebo to standard symptomatic drugs over 12 to 18 months. Delaying progression to disease milestones may offer additional validity to these studies. It is unclear if biological and neuroimaging markers will add to the clinical evidence.

The antiplatelet drugs, commonly used in the prevention and treatment of cerebrovascular disease, possess a number of effects that are independent of direct antiplatelet actions. Beneficial and detrimental effects both occur. The endothelium is an important mediator of these non-antiplatelet effects. We performed a literature search to locate articles related to acetylsalicylic acid (aspirin), clopidogrel, ticlopidine, and dipyridamole and the interactions of these medications with the endothelium. The role of each of the above medications is explored in relation to vasodilation, inflammation, oxidation, platelet-leukocyte interactions, and thrombogenic tendency via platelet-vessel wall interactions.

Dopamine (DA) receptors, which are heavily expressed in the caudate/putamen of the brain, represent the molecular target of several drugs used in the treatment of various neurological disorders, such as Parkinson's disease. Although most of the drugs are very effective in alleviating the symptoms associated with these conditions, their long-term utilization could lead to the development of severe side-effects. In addition to uncovering novel mediators of physiological DA receptor functions, recent research advances are suggesting a role of these receptors in toxic effects on neurons. For instance, accumulating evidence indicates that DA receptors, particularly D1 receptors, are central in the neuronal toxicity induced by elevated synaptic levels of DA. In this review, we will discuss recent findings on DA receptors as regulators of long term neuronal dysfunction and neurodegenerative processes.

Félix Vicq d'Azyr was born in 1748 in the small town of Valognes, Normandy. He studied medicine in Paris but he was particularly impressed by the lectures given at the Jardin du Roi by the comparative anatomist Louis Daubenton and the surgeon Antoine Petit. In 1773, Vicq d'Azyr initiated a series of successful lectures on human and animal anatomy at the Paris Medical School, from which he received his medical degree in 1774. He was elected the same year at the Academy of Sciences at age 26, thanks to his outstanding contributions to comparative anatomy. Vicq d'Azyr became widely known after his successful management of a severe cattle plague that occurred in the southern part of France in 1774, an event that led to the foundation of the Royal Society of Medicine in 1778. As Permanent Secretary of this society, Vicq d'Azyr wrote several eulogies that were models of eloquence and erudition and worth him a seat at the French Academy in 1788. Vicq d'Azyr published in 1786 a remarkable anatomy and physiology treatise: a large in-folio that contained original descriptions illustrated by means of nature-sized, colored, human brain figures of a quality and exactitude never attained before. In 1789, Vicq d'Azyr was appointed physician to the Queen Marie-Antoinette and, in 1790, he presented to the Constituent Assembly a decisive plan to reform the teaching of medicine in France. Unfortunately, Vicq d'Azyr did not survive the turmoil of the French Revolution; he died at age 46 on June 20, 1794.

Primary Sjögren's syndrome (PSS) mainly affects exocrine glands and is clinically characterized by keratoconjunctivitis sicca and xerostomia. Among several possible extraglandular manifestations, involvement of the peripheral nervous system may occur with reported frequencies from 10% to 60%. Peripheral nerve manifestations constitute sensory neuropathy, including sensory ganglioneuronopathy, sensorimotor, including polyradiculoneuropathy and demyelinating neuropathy, motor neuropathy, multiple mononeuropathy, trigeminal and other cranial neuropathies, autonomic neuropathy, and mixed patterns of neuropathy. Knowledge of the neurological manifestations of PSS is hampered by evolving classification criteria of PSS over the years, and by use of highly selected patient populations on the basis of a primary neurological diagnosis. Sural nerve biopsy may show vascular or perivascular inflammation of small epineurial vessels (both arterioles and venules) and in some cases necrotizing vasculitis. Loss of myelinated nerve fibers is common and loss of small diameter nerve fibers occurs. Pathology in cases of sensory ganglioneuronopathy consists of loss of neuronal cell bodies and infiltration of T cells. Peripheral neuropathy in PSS often is refractory to treatment although newer biological agents may provide more effective treatment options. Current treatment strategies used in autoimmune neuropathies may be tried depending upon characteristics of the neuropathy and results obtained by a thorough clinical and laboratory investigation.

In the era of chronic disease, we are challenged to find therapies that provide symptomatic relief and ideally, alter the course of the underlying disease. In Alzheimer's disease (AD), these issues are complicated by the disease itself, which affects the subject's decision-making capacity for participation in the research. According to established ethical guidelines it is clear that individuals with impaired capacity may participate in research and their risk should be no greater than that which the individual would have in day to day activities with anticipation of benefits within that realm. Decision making processes are complex and involve proxies who themselves have biases about their loved one and the potential for participating in the research. Newer disease-modifying approaches such as immunotherapy have potential for affecting the course of the underlying disease but with greater risk of more significant side effects. Ideally the health care of the subjects is not disadvantaged by research participation. At the same time, trials of potentially riskier therapy are relevant in subjects with the disease. Research for subjects with AD must have appropriate safeguards in place to enable effective progress in innovative therapy for a vulnerable, often elderly population. Recommendations are made which could further our capacity to undertake ethical research in the AD population.

In the 1700's a strange new disease affecting sheep was recognized in Europe. The disease later became known as “Scrapie” and was the first of a family of similar diseases affecting a number of species that are now known as the Transmissible Spongiform Encephalopathies (TSEs). The appearance of a new disease in humans linked to the consumption of meat products from infected cattle has stimulated widespread public concern and scientific interest in the prion protein and related diseases. Nearly 300 years after the first report, these diseases still merit the descriptor “strange”. This family of diseases is characterized by a unique profile of histological changes, can be transmitted as inherited or acquired diseases, as well as apparent sporadic spontaneous generation of the disease. These diseases are believed by many, to be caused by a unique protein only infectious agent. The “prion protein” (PrPC), a term first coined by Stanley Prusiner in 1982 is crucial to the development of these diseases, apparently by acting as a substrate for an abnormal disease associated form. However, aside from being critical to the pathogenesis of the disease, the function of PrPC, which is expressed in all mammals, has defied definitive description. Several roles have been proposed on the basis of in vitro studies, however, thus far, in vivo confirmation has not been forthcoming. The biological features of PrPC also seem to be unusual. Numerous mouse models have been generated in an attempt to understand the pathogenesis of these diseases. This review summarizes the current state of histological features, the etiologic agent, the normal metabolism and the function of the prion protein, as well as the limitations of the mouse models.

Clinical trials in persons with dementia bring into focus the ethical dilemmas frequently confronting the clinician-scientist. Despite the existence of various ethical guidelines, most with common underlying principles, few are specific to dementia. A particular difficulty is finding a balance between respect for the autonomy of the individual and the protection of vulnerable persons, while at the same time defining an acceptable risk/benefit ratio for the study. The availability of symptomatic treatments for Alzheimer's disease also now make it difficult to argue that withholding treatment from those in the placebo arm of a clinical trial fulfills one's duty to provide best care. Those conducting clinical trials must be knowledgeable about existing legislation and ethical guidelines in order to justify to themselves and others, the design of clinical trials and their risks. They must be prepared to educate patients and family members about dementia and research, determine each potential subject's competence to consent, and ensure that decisions about participation are in accordance with the best interests of the subject. Ethical conduct of clinical trials of new antidementia therapies will require that everyone involved understands the values and beliefs that guide their decision-making and the potentially conflicting roles facing the clinician-scientist.

A brief review of previous studies is presented on tonotopic organization of primary auditory cortex (AI) in humans. Based on the place theory for pitch perception, in which place information from the cochlea is used to derive pitch, a well-organized layout of tonotopic map is likely in human AI. The conventional view of tonotopy in human AI is a layout inwhich the medial-to-lateral portion of Heschl's gyrus represents high-to-low frequency tones. However, we have shown that the equivalent current dipole (BCD) in auditory evoked magnetic fields in the rising phase of N100m response dynamically moves along the long axis of Heschl's gyrus. Based on analyses of the current sources for high-pitched and low-pitched tones in the right and left hemispheres, we propose an alternative tonotopic map in human AI. In the right AI, isofrequency bands for each tone frequency are parallell to the first transverse sulcus; on the other hand, the layout for tonotopy in the left AI seems poorly organized. The validity of single dipole modelling in the calculation of a moving source and the discrepancy as to tonotopic maps in the results between auditory evoked fields or intracerebral recordings and neuroimaging studies also are discussed. The difference in the layout of isofrequency bands between the right and left auditory cortices may reflect distinct functional roles in auditory information processing such as pitch versus phonetic analysis.

Myelination in the nervous system is a tightly regulated process that is mediated by both soluble and non-soluble factors acting on axons and glial cells. This process is bi-directional and involves a variety of neurotrophic and gliotrophic factors acting in paracrine and autocrine manners. Neuron-derived trophic factors play an important role in the control of early proliferation and differentiation of myelinating glial cells. At later stages of development, same molecules may play a different role and act as inducers of myelination rather than cell survival signals for myelinating glial cells. In return, myelinating glial cells provide trophic support for axons and protect them from injury. Chronic demyelination leads to secondary axonal degeneration that is responsible for long-term disability in primary demyelinating diseases such as multiple sclerosis and inherited demyelinating peripheral neuropathies. A better understanding of the molecular mechanisms controlling myelination may yield novel therapeutic targets for demyelinating nervous system disorders.