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Multiple sclerosis is characterized by both demyelination and neurodegeneration. The lack of myelin in the retina makes this an ideal structure in which to visualize the latter process. In this Review, Frohman et al. describe the novel use of retinal imaging technology, and in particular optical coherence tomography (OCT), to model the disease process in multiple sclerosis. They suggest that OCT could ultimately be used to identify strategies aimed at neuroprotection in the CNS.
The management of pain that is refractory to conventional treatments represents a considerable challenge for clinicians. Botulinum toxin has recently emerged as a potential novel approach to the control of refractory pain, and in this article Bahman Jabbari weighs up the available evidence for the efficacy of botulinum toxin therapy in various pain syndromes, including cervical dystonia, headache, neuropathic pain and postoperative pain.
Despite remarkable success in the fight against leprosy, the disease remains an important public health problem. This Review focuses on the neurological manifestations of leprosy and the pathophysiology of nerve damage. Special emphasis is given to developments in the early detection and treatment of leprosy-related nerve impairment.
Therapeutic approaches to febrile seizures have changed since the 1970s when the main reference studies on this topic were published. It is, therefore, timely to consider whether outcomes of febrile seizures have changed in the intervening years. Here, Chungath and Shorvon assess data published since 1993 with respect to three outcomes: mortality, later development of afebrile seizures or epilepsy, and hippocampal or mesial temporal sclerosis.
Mitochondrial dysfunction and oxidative stress have been strongly implicated in the pathogenesis of Parkinson disease (PD), and the products of several PD-associated genes become localized to the mitochondria under certain conditions. In this article, Henchcliffe and Beal review recent developments in mitochondrial biology that have contributed to our understanding of the disease process in PD, and they discuss how this knowledge might aid in the development of 'mitochondrial therapies' for PD.
Over the past few years, evidence has accumulated to indicate that B cells have a pivotal role in the pathogenesis of various autoimmune neurological disorders, including multiple sclerosis, myasthenia gravis and inflammatory myopathies. In this article, Marinos Dalakas highlights the roles of B cells in these and other autoimmune disorders, and summarizes the experience to date with anti-B-cell therapies, focusing particularly on the B-cell-depleting monoclonal antibody rituximab.
Waldenstrom's macroglobulinemia—a condition that is characterized by overproduction of IgM antibodies and most commonly occurs in lymphoplasmacytic lymphoma—is often accompanied by nervous system complications, such as peripheral neuropathy or complications related to serum hyperviscosity. This Review provides an overview of the diagnosis and treatment of such neurological manifestations.
In mammalian neurons, cation–chloride cotransporters (CCCs) have vital roles in regulating the intracellular chloride concentration—which in turn determines the strength and polarity of γ-aminobutyric-acid-mediated neurotransmission—and in cell volume homeostasis. In this Review, Kahle et al. consider how breakdowns of chloride homeostasis resulting from alterations in CCC activity might contribute to various neurological disorders, including seizures and neuropathic pain, and they discuss the potential of CCCs as targets for novel therapeutic strategies.
Muscle strength is believed to be an important factor contributing to postural control, yet surprisingly few studies have explicitly examined the relationship between muscle weakness and postural instability. In this article, Horlings et al. search the current literature for evidence indicating that muscle weakness is a risk factor for falls, citing studies performed in elderly individuals and in patients with focal muscular deficits. In addition, they consider the effects of muscle strength training on falls and balance measures.
Migraine is a common neurological disorder, which, according to figures from US population studies, affects around 18% of women and 6% of men. In this Review, Stephen Silberstein highlights the approach to acute and preventive migraine treatment in the US, drawing on his own experiences at the Headache Center at Thomas Jefferson University Hospital.
In spite of recent advances in surgical and medical therapies, the prognosis for patients diagnosed with the high-grade glioma glioblastoma multiforme remains poor. In this Review, Das et al. present evidence that the resistance of these tumors to current therapies is attributable to a small subpopulation of cancer stem cells, and they consider potential new therapeutic strategies that specifically target this cell population.
Desynchronization of circadian rhythms is a common occurrence in individuals presenting with sleep disorders. In this Review, Pandi-Perumal et al. highlight the roles of light and endogenous melatonin in the synchronization of sleep–wake rhythms and rest–activity cycles with the light–dark cycle, and they discuss how light therapy and exogenous melatonin might be used to treat circadian rhythm sleep disorders.
Regulatory T (TREG) cells are emerging as key players in the pathogenetic scenario of CNS autoimmune inflammation. In this article, Zozulya and Wiendl discuss how TREG-cell dysfunction might influence the disease course in multiple sclerosis and experimental autoimmune encephalomyelitis, highlighting the importance of interactions between TREGcells and dendritic cells. The authors also assess the potential for therapeutic use of these cell types in patients with multiple sclerosis.
Bulbar symptoms such as impaired swallowing and speech impairment are frequent features of amyotrophic lateral sclerosis and can markedly reduce life expectancy and quality of life. In this article, Kühnlein et al. highlight the importance of early detection, as well as appropriate treatment and management, of bulbar symptoms in patients with amyotrophic lateral sclerosis, emphasizing the benefits of a multidisciplinary approach.
Central retinal artery occlusion (CRAO) is an acute stroke of the eye that can result in profound visual impairment. Standard noninvasive therapies do not markedly alter the natural history of CRAO, and this has prompted investigations into new treatment strategies. As Chen and Lee discuss in this Review, thrombolytic therapy—especially local intra-arterial fibrinolysis—is showing considerable promise for the acute management of acute CRAO.
Long-term immunosuppression is often necessary in chronic autoimmune conditions such as myasthenia gravis. In this article, Sivakumar Sathasivam examines the mechanisms of action of steroids and other immunosuppressants, reviews randomized and nonrandomized evidence for their efficacy in generalized myasthenia gravis, and provides recommendations regarding the use of each immunosuppressant in the treatment of this condition.
Itch is a common symptom of inflammatory skin disorders, but it can also occur as a result of damage to the itch-mediating nervous system, in which case it is known as neuropathic itch. In this Review, Binder et al. describe the mechanisms underlying itch generation, introduce a classification system for itch, and propose a mechanism-based management approach to chronic neuropathic itch. The topic of neuropathic itch is explored further in an accompanying Case Study in this issue.
Signal detection theory was developed during the Second World War as a means to improve the ability of radar operators to spot enemy bombers. In this article, Oliver et al. explain how an overworked neurologist might use signal detection theory in the clinic to sift out important information from the often bewildering array of visual, verbal and auditory cues that constitute a patient's history and examination.
Sleep disturbances, such as insomnia, rapid eye movement sleep disorders and excessive daytime sleepiness, are symptoms that are commonly associated with movement disorders. This article discusses the prevalence and underlying mechanisms of sleep disturbances in patients with Parkinson's disease or atypical parkinsonism, and proposes therapeutic approaches that could benefit both the patient and their sleeping partner.
