Reviews & Analysis

The decision whether to withdraw antiepileptic drugs in adults who have been seizure-free for 2 years is a difficult one, with relief from adverse events weighing against the possibility of seizure recurrence with all its consequences. In this Viewpoint, Alla Guekht calls on clinicians not to dismiss lightly the risk of relapse.

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.

This Case Study describes an 18-year-old woman who presented to a stroke center with dysphasia and right hemiparesis. The patient was diagnosed with cocaine-induced cerebral vasculitis. BOLD MRI cerebrovascular reactivity findings were particularly useful in the diagnosis and follow-up of this case, and the authors point to the technique's potential for imaging cerebral vasculitis in general.

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.

The concept of consciousness has evolved as technology has progressed, and our understanding of coma and disorders of consciousness has deepened accordingly. In this Viewpoint, Steven Laureys traces the beginnings of coma research and shows how the introduction of functional neuroimaging has revolutionized this field.

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.

Functional neuroimaging is emerging as a novel tool to evaluate patients with disorders of consciousness. This Viewpoint looks at one of the most vexing ethical challenges resulting from this development: how should doctors react if families request a functional MRI scan for a loved one who is in a limited state of consciousness?

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.

This article discusses the case of a 40-year-old man with basilar artery thrombosis, which, after numerous investigations, was found to be attributable to cocaine use. The authors highlight the importance of asking patients about cocaine exposure as part of a routine cardiovascular history, and they provide the first description of the use of thrombolysis to treat cocaine-induced stroke.

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.

This article describes the case of a 54-year-old man who experienced recurrent episodes of transient amnesia over a number of years. The patient was diagnosed with transient epileptic amnesia, and his case provides the first radiological evidence that this syndrome can result from seizure activity in the hippocampus.

This Case Study describes in detail a case of progranulin-associated frontotemporal lobar degeneration (FTLD). The patient was initially asymptomatic, but developed progressive brain atrophy and deficits on neuropsychological testing before the clinical onset of cognitive impairment. The authors use this case as a springboard to discuss advances in the genetics of FTLD with an emphasis on the importance of serial cognitive testing and neuroimaging.

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.

Against the background of the debate about the best models of stroke unit care, Lenzi and Di Piero present their argument that patients with stroke have better outcomes if their stay in a dedicated stroke unit is extended, enabling prolonged and intensive monitoring for stroke complications.

This Viewpoint contributes to the topical debate on the therapeutic benefits of deep brain stimulation in Parkinson's disease (PD). The authors argue that there is more to this treatment approach than just providing symptomatic benefits, and suggest that it may actually become the first therapy proven to slow the progression of PD.

Regulatory T (T_REG) cells are emerging as key players in the pathogenetic scenario of CNS autoimmune inflammation. In this article, Zozulya and Wiendl discuss how T_REG-cell dysfunction might influence the disease course in multiple sclerosis and experimental autoimmune encephalomyelitis, highlighting the importance of interactions between T_REGcells and dendritic cells. The authors also assess the potential for therapeutic use of these cell types in patients with multiple sclerosis.