Review Articles in 2011

Depression is a common symptom in patients with Parkinson disease (PD), and is found at higher rates in these individuals than in healthy populations or patients with other neurodegenerative disorders. Aarsland et al. discuss both the course of depression and the mechanisms that may contribute to the enhanced susceptibility to depression in patients with PD. Management strategies to control depression in these individuals are also highlighted.

Defects in autophagy—a process that enables the degradation of unwanted or damaged intracellular proteins and organelles—are associated with the accumulation of aggregate-prone proteins. Defects in neuronal autophagy may have a role in neurodegenerative disease that are associated with aberrant protein accumulation, such as Alzheimer disease and Parkinson disease. Rubinsztein and Harris discuss how defects in autophagic pathways might cause these diseases and highlight how autophagy-modulating drugs might be used as therapy.

Cases of postural tachycardia syndrome (PoTS) have been described dating back to the 19^thcentury; however, the condition remains poorly understood, and the diagnosis is not readily made. Mathias and colleagues provide a comprehensive Review detailing the characteristics and possible pathophysiological mechanisms of PoTS, as well as investigation and treatment.

Lesion activity detected on MRI scans has become an accepted surrogate for disease activity in relapsing–remitting multiple sclerosis (MS). Barkhof and colleagues provide key recommendations for efficient use of MRI in clinical trials for relapse-onset MS, including practical issues related to acquisition, analysis and reporting of MRI data, approaches to optimization of trial design, and safety considerations.

Multifocal motor neuropathy (MMN) is a rare inflammatory disorder that features slowly progressive, asymmetric distal limb weakness. Leonard van den Berg and colleagues describe the diagnostic criteria for MMN, which are important for distinguishing this disease from mimic disorders such as amyotrophic lateral sclerosis. The authors also discuss the pathophysiology of MMN, emphasizing the role of GM1-specific autoantibodies, and outline current treatment options and possible new therapeutic strategies.

Tourette syndrome, characterized by motor or vocal tics, is a multifactorial neurodevelopmental disorder that affects up to 1% of children and adults worldwide. In this Review, McNaught and Mink describe the history of Tourette syndrome and its clinical presentation, and provide an overview of its epidemiology and pathophysiology. Current treatment strategies and potential future therapies are also discussed.

Neuropsychological assessment can identify deficits in brain function that assist in the diagnosis of patients with dementing illness. Fields et al. highlight the unique properties of neuropsychological measurements, including their role as biomarkers of dementia, in differentiating diseases with similar topographies, and in predicting the risk of dementia. Prediction of functional decline on the basis of these measurements will assist in planning of the future care requirements for patients at risk of dementia.

An improved understanding of the cellular events that lead to motor neuron injury in amyotrophic lateral sclerosis (ALS) could highlight promising new therapeutic strategies. Pamela Shaw and colleagues provide a comprehensive overview of the numerous molecular mechanisms that are involved in ALS, including oxidative stress, mitochondrial dysfunction and excitotoxicity. They discuss features specific to motor neurons that might render this cell type vulnerable to damage, and highlight important links between cellular events and clinical features of the disease.

Most patients who present with longitudinal extensive transverse myelitis (LETM) are diagnosed with neuromyelitis optica (NMO). Trebst et al. use case studies of patients without NMO who presented with spinal lesions to show the variety of different etiologies that can underlie LETM. The authors highlight the diagnostic indicators and difficulties encountered in making differential diagnoses in these patients.

Until the early 1990s, the prevailing view was that amyotrophic lateral sclerosis (ALS) was rarely familial, but subsequent genetic discoveries have overturned this idea. Andersen and Al-Chalabi document the rapidly changing genetic landscape in ALS, highlighting the lack of a clear distinction between heritable and apparently sporadic ALS, and providing recommendations for genetic counseling.

Research into amyotrophic lateral sclerosis (ALS) has improved our understanding of the molecular mechanisms underlying disease pathogenesis, but diagnosis of patients with ALS has remained difficult. Bowseret al. highlight recent discoveries of biomarkers for ALS—from proteins in biofluids to neurophysiological and neuroimaging findings—and discuss the benefits and limitations of these biomarkers as diagnostic and prognostic indicators of disease.

Amyotrophic lateral sclerosis is a devastating neurodegenerative motor neuron disease that results in progressive loss of bulbar and limb function. In this Review, Hardiman et al. provide an overview of the clinical aspects of the disease, discussing epidemiology, clinical presentation, diagnosis and management, with an emphasis on recent key advances.

Intracranial arterial aneurysms can pose life-threatening risks to patients, so understanding the cause and the progression of these lesions is important for choosing the right treatment. This Review argues that aneurysms are a symptom of an underlying vascular disease rather than constituting a disease on their own. The authors classify intracranial aneurysms by vessel wall pathology and demonstrate that knowledge of the morphology and pathology of this structure is important in determining the therapeutic approach.

Neurostimulation therapy is often needed for patients with neuropathic pain that is refractory to medical treatment. In this Review, Nguyenet al. compare and contrast the evidence for efficacy of motor cortex stimulation and deep brain stimulation, highlighting the brain-targeting strategies, mechanisms of action and future therapeutic potentials of both treatments in patients with chronic neuropathic pain.

Neurocysticercosis (caused by infection with the tapewormTaenia solium) is a major cause of acquired seizures and epilepsy worldwide. Nash and Garcia describe the different types of neurocysticercosis infection and discuss the role of the host inflammatory response in disease pathology. They also highlight recent advances in the diagnosis and treatment of the disease, including the limitations of current therapies.

Neuropathy is the most common complication of diabetes and considerably reduces patient quality of life, yet no disease-modifying therapies are currently available and symptomatic treatments generally provide only partial relief. Vincent and colleagues provide an update on the cellular mechanisms that lead to diabetic neuropathy, which involves a complex interplay between oxidative and inflammatory pathways in neurons, Schwann cells and the microvascular endothelium. The authors highlight potential new therapeutic targets and discuss drug candidates that are in development for this debilitating diabetic complication.

Research has shown that Huntington disease, a progressive and fatal neurodegenerative disorder resulting from polyglutamine expansion in the huntingtin protein, is associated with changes in cellular cholesterol metabolism. Drawing on data from clinical and animal studies, Karasinska and Hayden discuss the roles of cholesterol in the CNS and describe the current state of knowledge of cholesterol dysregulation in Huntington disease.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common chronic autoimmune neuropathy. In this Review, Marinos Dalakas provides an update on the diagnosis of this disease, including recently devised consensus criteria. CIDP treatments—primarily corticosteroids, intravenous immunoglobulin and plasmapheresis—and ongoing challenges in trial design are discussed, together with potential therapeutic approaches that are emerging from advances in our understanding of the underlying immunopathology of this disease.

Pain is common in patients with multiple sclerosis (MS) and can be difficult to diagnose and manage. Solaro and Messmer Uccelli provide a summary of the available data on pharmacological approaches to pain management in MS, including the different treatment options for neuropathic and nociceptive pain, and highlight the need for further clinical trials in this field.

As the mortality rates of premature and newborn babies have decreased, the incidence of neurological morbidity in these neonates has increased. Bonifacio et al. highlight advances in the care of neonates who have sustained a neurological insult, discussing available treatments and therapies, and the utility of brain monitoring techniques to predict long-term neurological outcomes. They also present a new model of care for the treatment of neonates with brain injury.