Recent advances in the pathogenesis of diabetic neuropathy

Recent advances in the understanding of the pathogenesis of diabetic neuropathy have been made in six areas. There is support for the notion that a reduction in nerve free myoinositol may be responsible in part for the nerve conduction slowing in diabetic neuropathy. There is further evidence of microvascular abnormalities, including morphometric evidence of multifocal fiber loss and of capillary changes in biopsied sural nerve. There is evidence of endoneurial hypoxia, including the findings of reduced nerve blood flow and endoneurial oxygen tensions in chronic experimental diabetic neuropathy (EDN). The major mechanisms of resistance to ischemic conduction failure (RICF) is the marked increase in nerve energy substrates. Recent studies provide certain insights into clinical characteristics of human diabetic neuropathy (HDN), including the asymmetric pattern of HDN, the paradox between liability to pressure palsies and RICF, and insulin-related acute painful neuropathy. The suggested pathogenetic scheme incorporates the notion that once hypoxia is established, it may start a vicious cycle of further capillary damage and escalating hypoxia.     

Recent advances in neurotrauma

The frequency of and outcome from acute traumatic brain injury (TBI) in humans are detailed together with a classification of the principal focal and diffuse pathologies, and their mechanisms in extract laboratory models are outlined. Particular emphasis is given to diffuse axonal injury, which is a major determinant of outcome. Cellular and molecular cascades triggered by injury are described with reference to the induction of axolemmal and cytoskeletal abnormalities, necrotic and apoptotic cell death, the role of Ca2+, cytokines and free radicals, and damage to DNA. It is concluded that TBI in humans is heterogeneous, reflecting various pathologies in differing proportions in patients whose genetic background (APOE gene polymorphisms) contributes to the outcome at 6 months. Although considerable progress has been made in the understanding of TBI, much remains to be determined. However, a deeper understanding of the pathophysiological events may lead to the possibility of improving outcome from rational targeted therapy.     

Recent advances in epilepsy

We have reviewed some of the important studies published within the last 18 months that have advanced our understanding of the epilepsies, their aetiology and treatment. Clinical studies have revealed new insights into old themes including seizure prediction, mortality in epilepsy, febrile seizures and the pathophysiology of focal cortical dysplasias. The rapid advances in genetics and particularly whole exome sequencing have had an impact on our understanding of epileptic encephalopathies, and the aetiology of hippocampal sclerosis. Experimental research techniques such as viral vector gene delivery, optogenetics and cell based transplantation techniques have set the framework for novel approaches to the treatment of pharmacoresistant epilepsy. These few examples are indicative of the great strides that have recently been made in epilepsy research.     

Recent advances in epilepsy

Journal of Neurology - This paper reviews advances in epilepsy in recent years with an emphasis on therapeutics and underlying mechanisms, including status epilepticus, drug and surgical...     

Recent advances in polymyositis

The most typical clinical features of polymyositis (PM), the criteria of diagnosis and principles of treatment are outlined. An inflammatory disease of muscle, PM also frequently affects other organs such as the skin and hence the name dermatomyositis. The principal cardiac symptom is a peculiar disturbance of atrioventricular conduction, correlated with a specific anti-Ro autoantibody, present in 25% of patients. The etiology of PM is as yet unknown, although there is evidence for an autoimmune pathogenesis. It is frequently found in association with other immune-mediated diseases such as myasthenia gravis, pemphigus, immune-complex vasculitis and Sjogren syndrome. Laboratory investigations show hypergammaglobulinemia, a decrease of complement factors C3 and C4 and the presence of circulating immune complexes in 70% of patients. Very frequent, especially in cases of dermatomyositis, is a histologically detectable accumulation of IgG and complement in the walls of the intramuscular venous vessels. Cell-mediated hypersensitivity, emphasised formerly as highly significant in PM, has not been confirmed. The presence of specific antimyoglobin lymphocyto-toxicity, once considered to be the hallmark of muscle degeneration in PM, has been excluded by a number of laboratories. In a personal series of patients with various clinical forms of PM a severe loss of suppressor/cytotoxic lymphocytes was found in the peripheral blood and a relative increase in the first subset. These results support the hypothesis that a serious disturbance of immunoregulation is present in PM and is the cause of a multitude of immunological anomalies, the characterisation of which is under study.This work was supported by the Muscular Dystrophy Group of Great Britain     

Recent advances in nemaline myopathy

The nemaline myopathies constitute a large proportion of the congenital or structural myopathies. Common to all patients is muscle weakness and the presence in the muscle biopsy of nemaline rods. The causative genes are at least twelve, encoding structural or regulatory proteins of the thin filament, and the clinical picture as well as the histological appearance on muscle biopsy vary widely. Here, we suggest a renewed clinical classification to replace the original one, summarise what is known about the pathogenesis from mutations in each causative gene to the forms of nemaline myopathy described to date, and provide perspectives on pathogenetic mechanisms possibly open to therapeutic modalities.     

Recent advances in Huntington's disease

Huntington's disease is a progressive and fatal neurological disorder caused by the expansion of a CAG trinucleotide repeat in exon 1 of the gene coding for a protein of unknown function that has been named huntingtin. The exact cause of neuronal death in Huntington's disease is unknown; however, the leading hypothesis is that of excitotoxicity and apoptosis induced by a defect in energy metabolism that may be caused by oxidative stress. How mutant huntingtin might cause these processes is unknown. New animal and cell models provide insights into the mechanism of pathogenesis and the search for the development of effective therapies.     

Recent advances in paediatric neuro-oncology

PURPOSE OF REVIEW: Primary central nervous system malignancies incorporate a variety of tumours with diverse biology and clinical behaviour and represent the most common solid tumour entity of childhood, accounting for approximate 20-25% of all primary paediatric malignancies. Recent findings regarding the underlying tumour biology may open up new avenues of clinical trial design, particularly identifying possible targets for biological modifiers. Over the last 12-18 months a significant number of institutional and national studies have been reported which are likely to impact on the design of future clinical trials. RECENT FINDINGS: In low-grade gliomas, stereotactically guided conformal radiotherapy should lead to a significant reduction in radiation-associated late toxicity, while in selected groups of high-grade gliomas the use of adjuvant or neo-adjuvant chemotherapy may improve survival. Completeness of resection and use of adjuvant focal radiotherapy remains the most important prognostic factor for outcome in patients with ependymomas, although in infants the use of post-surgical chemotherapy alone may allow the postponing of radiotherapy in selected cases. In primitive neuroectodermal tumours prognostic biological markers have been identified that are undergoing prospective evaluation. For patients with localized medulloblastomas a new standard treatment is emerging that uses reduced-dose craniospinal radiotherapy followed by platinum-based chemotherapy, while in supratentorial primitive neuroectodermal tumours future treatment will be aimed at improving local control. SUMMARY: Given the rarity of paediatric primary central nervous system malignancies, further progress can only be achieved in the context of national or multinational prospective clinical trials incorporating biological studies, and participation in these should be strongly encouraged.     

Recent advances in infant botulism

Since infant botulism was first identified three decades ago, our understanding of botulinum toxins and the organisms that produce them has grown. A newer classification system now recognizes Clostridium baratii and Clostridium butyricum along with Clostridium botulinum as causative agents. Recently, increasing therapeutic use of botulinum toxins has sparked substantial new research into their mechanisms of action. This research, and some case reports from infants sickened by unusual botulinum toxins suggest that disease caused by different toxin types may result in varying clinical presentations. Perhaps most significantly for pediatricians and child neurologists, a specific treatment for infant botulism has just been approved. This article reviews the clinical presentation, diagnosis, and treatment of infant botulism, including human botulism immune globulin, and discusses the various organisms and toxins that cause this disease.     

Recent advances in headache research

The understanding of the pathophysiology of primary headache disorders, especially migraine, has substantially improved over the last two decades. As a result, migraine is now mainly considered to be a disorder of the brain, rather than the vasculature or the meninges. In addition, the insights of the complex pathophysiological mechanisms and the brain structures involved in the disease facilitate the development of new therapeutic approaches. At the recent Annual Meeting of the American Headache Society in Washington (DC, USA) the latest scientific advances, as well as their clinical implications, were highlighted.     

Recent advances in poststroke depression

Abstrazct Depression is the most common psychiatric complication after stroke. Its prevalence varies from 20% to 80%, and it is underdiagnosed and undertreated. It has significant impact on rehabilitation, motor recovery, activities of daily living, social and interpersonal life, and mortality. Several studies have shown that biological and psychosocial factors play significant roles in the development of this disabling disease. Recent research shows that neurochemical processes also may play some role in the pathophysiology of this condition. Several trials have shown evidence that the older, as well as newer antidepressants and psychostimulants may reduce/prevent depressive symptoms after stroke. At this point there are no clear guidelines available to choose safe and effective treatments. Drugs are selected based on their efficacy and side effect profile in these patients. More research is needed to understand the pathophysiology of depression after stroke. There also is a need for more randomized clinical trials to better treat patients with this condition.     

Recent advances in compulsive hoarding

Compulsive hoarding is a common and often disabling neuropsychiatric disorder. This article reviews the conceptualization, phenomenology, diagnosis, etiology, neurobiology, and treatment of compulsive hoarding. Compulsive hoarding is part of a discrete clinical syndrome that includes difficulty discarding, urges to save, excessive acquisition, indecisiveness, perfectionism, procrastination, disorganization, and avoidance. It was thought to be part of obsessive-compulsive disorder or obsessive-compulsive personality disorder, but recent evidence indicates that it should be classified as a separate disorder with its own diagnostic criteria. Compulsive hoarding is a genetically discrete, strongly heritable phenotype. Neuroimaging and neuropsychological studies are elucidating its neurobiology, implicating dysfunction of ventral and medial prefrontal cortical areas that mediate decision-making, attention, and emotional regulation. Effective treatments include pharmacotherapy and cognitive-behavioral therapy. More research will be required to determine the prevalence, etiology, and pathophysiology of compulsive hoarding and to develop better treatments     

Recent advances in neuroendovascular therapy

The field of neurointerventional surgery has grown in recent years. Endovascular therapies for both ischemic stroke and intracranial aneurysms have become important components in the multimodal treatment of these conditions. Familiarity with these treatment options by general neurologists is important for patient care. This article reviews recent trials and devices representing important advances in the field.