Reviews & Analysis

Protein misfolding and aggregation occur in most neurodegenerative disorders, but the concept of spreading and infectivity of aggregates in the CNS has, until recently, been confined to prion diseases such as Creutzfeldt–Jakob disease. New evidence suggests that prion-like spreading, involving proteins such as amyloid-β, tau, huntingtin and α-synuclein, can occur in other neurodegenerative disorders. In this article, Lee et al. discuss the underlying molecular mechanisms and consider the therapeutic implications of the new data.

Impaired decision-making is a clinical symptom associated with a number of neurodegenerative diseases. In this article, Gleichgerrcht et al. review the neural basis of decision-making cognition in relation to the neuroanatomical changes associated with neurodegenerative diseases. The authors also suggest a number of recommendations that future studies could adopt to aid our understanding of decision-making cognition.

Botulinum neurotoxin (BoNT) is an effective treatment for a wide range of conditions that are frequently seen in the neurology clinic. In this article, Lim and Seet provide an overview of the mechanisms of action of BoNT and its use in the treatment of conditions such as dystonia, spasticity, essential tremor, hemifacial spasm and headaches. Important practical considerations, such as the reconstitution of BoNT, dosing, and methods of administration, are also reviewed.

A new study indicates that deep brain stimulation (DBS) plus best medical therapy markedly improves quality of life of patients with advanced Parkinson disease compared with best medical therapy alone. The frequency of serious adverse events related to DBS was similar to that reported in other DBS trials, underscoring the need for careful patient selection and counseling for this invasive therapy.

Bacterial meningitis causes substantial neurological morbidity and mortality worldwide. The use of corticosteroids as adjunctive therapy to antibiotics has been studied in clinical trials and debated for decades. A new meta-analysis attempts to reconcile some of the disparate findings from trials in this field.

After a stroke, seizures and later development of epilepsy can have a devastating impact on patient outcome and quality of life. Predicting the risk of developing poststroke epilepsy is currently an inexact science, and improving the accuracy of this process could lead to more-targeted use of prophylactic antiepileptic drugs for a defined period of time.

Malignant gliomas are aggressive tumors that often progress despite multimodality therapy. At recurrence, treatment approaches must balance the potential morbidity of a given therapy against the survival benefit that might be achieved. A new study reports that irradiation in this setting is well tolerated and could prolong survival.

Deep brain stimulation of the subthalamic nucleus or the internal pallidum can be an effective treatment for the disabling motor complications arising from dopaminergic treatment for Parkinson disease. The subthalamic nucleus has emerged as the preferred target for such treatment; however, no data exist to guide the choice between these two sites.

Intracerebral hemorrhage (ICH) carries a high risk of morbidity or death, and no effective therapies are available to combat this condition. In this article, Adeoye and Broderick discuss the natural history of such hemorrhages before providing an overview of medical and surgical ICH clinical trials that have been completed or initiated within the past decade.

Multiple sclerosis is an incurable condition that introduces great uncertainty into virtually all aspects of a person's life. In this Review, Simmons considers the ways in which this uncertainty is being addressed by improved diagnostic tools, advances in immunotherapy, multidisciplinary rehabilitation, community programs, and provision of information specifically designed to facilitate shared decision-making and empowerment. He discusses these issues in the context of three philosophical frameworks: the biomedical, biopsychosocial and sociopolitical models.

Extreme hypoglycorrhachia is usually caused by bacterial meningitis; however, suspicion should be raised if a patient with persistent extreme hypoglycorrhachia, pleocytosis and negative microbiological studies remains refractory to antimicrobial therapy. Viola describes the case of a 55-year-old man with chronic leptomeningitis and persistent hypoglycorrhachia, who was found to have Currarino syndrome. This syndrome is a complex genetic disorder that includes the following triad: sacral bony defect, presacral mass, and an anorectal malformation. Leptomeningitis in this patient was attributed to cholesterol crystals contained in a large presacral cyst with a communicating fistula to the CNS.

Surgical intervention can represent an effective treatment for some patients with medically refractory epilepsy. In this Review, Duncan explores the various imaging techniques that can be used in epilepsy surgery to identify the epileptic source and/or to reduce the risk of surgery-related morbidity. In addition to examining established clinical practice, Duncan highlights recent advances in this field.

Neuroimaging is highly recommended in the diagnosis and management of acute stroke, including disease characterization, and monitoring of responses to medical interventions. In this Review, Merino and Warach consider the diagnostic information that clinicians might gain from CT and MRI scanning of patients with suspected stroke, and the relative advantages and drawbacks of these imaging techniques.

Diabetes has been implicated to be a risk factor for Alzheimer disease (AD), but the underlying biological mechanisms that link the development of diabetes and AD are not fully understood. In this article, Sims-Robinson et al. summarize the mechanistic pathways that might link these two age-related diseases and discuss the possible points of intervention that future therapies could exploit to treat AD.

Over the past 300 years, the migraine field has been dominated by two theories—the vascular theory and the central neuronal theory. The vascular theory was bolstered by the finding that vasoconstrictors are effective in acute migraine treatment, but evidence is now emerging that vasodilatation is neither necessary nor sufficient to trigger a migraine attack. Ho et al. consider the evidence pointing towards a neuronal mechanism in migraine development, highlighting the role of calcitonin gene-related peptide and its receptors.

A 2009 study found that cerebral venous drainage was impaired in all patients with multiple sclerosis examined, but was not affected in control individuals. The study's investigators suggested that venous obstruction in the neck—a treatable condition—caused perivenous inflammation and demyelination. A comprehensive ultrasound study has now challenged this hypothesis.

A large, retrospective study indicates that in patients with acute ischemic stroke, endovascular interventions performed under conscious sedation carry a lower risk of poor neurological outcome and mortality than those performed under general anesthetic. Owing to a number of potential confounding factors, however, the results must be interpreted with caution.

Antiepileptic drug randomized controlled trial (RCT) design has been criticized for its emphasis on regulatory, licensing aspects rather than clinical considerations. A new study that scrutinized RCT patient recruitment has also raised important ethical issues. At a time when RCT patient recruitment in resource-poor countries is increasing, changes in RCT design seem imperative.

Malformations of cortical development are commonly associated with epilepsy and intellectual disabilities. Polymicrogyria is one of the most frequent cortical malformations but remains largely enigmatic. A new multicenter clinical and radiographic study of patients with polymicrogyria has identified anatomical patterns that could shed new light on the underlying pathogenesis of this condition.

Noninvasive therapies such as cognitive intervention could aid the prevention and treatment of Alzheimer disease (AD). In this article, Buschert et al. provide an overview of the current knowledge relating to the use of cognitive intervention in patients with AD, and discuss recent findings that indicate that this treatment provides substantial benefits for patients with cognitive deficits. The authors also review recent studies that have used neuroimaging techniques to identify biological changes within the brain that are associated with cognitive intervention.