Review Articles in 2013

Over the past 15 years, the contribution of genetic factors to development of Parkinson disease has been increasingly recognized. In their Review, Trinh and Farrer summarize the latest findings in this field, highlighting overlapping results from diverse genetics studies. Together, the genes identified suggest a key role for impaired vesicle and mitochondrial dynamics in neurons, which could represent promising targets for novel therapies in Parkinson disease.

Mitochondrial diseases are a complex and clinically heterogeneous group of disorders, which— together with our poor understanding of the underlying pathology—makes their diagnosis difficult. Here, DiMauro et al. review current knowledge of defects of the mitochondrial respiratory complex that lead to neurological mitochondrial disorders, outlining diagnostic clues for each disorder, and discussing current therapeutic approaches for these often devastating diseases.

Chronic low back pain (CLBP) is a highly prevalent and debilitating disorder. Despite progress in understanding the aetiology of CLBP in recent years, this knowledge has not been translated into decreased prevalence or new therapies. In this Review, Morlion discusses interventional pain management, as well as surgical and pharmacotherapy approaches, and reviews the current evidence for the efficacy of these treatments in CLBP.

In this Review, Reindl et al. discuss a range of CNS disorders that are known to be associated with autoantibodies against myelin oligodendrocyte glycoprotein (MOG). They examine the experimental evidence for a role for MOG autoantibodies in the pathogenesis of demyelinating CNS disorders such as multiple sclerosis and acute disseminated encephalomyelitis, and explore the potential of MOG to function as a biomarker in these diseases.

The pathological underpinnings of Alzheimer disease (AD) are now known to begin up to two decades before manifestation of clinical disease, and intervention during preclinical AD stages is increasingly recognized as key to therapeutic success. Here, Eric Reiman and colleagues discuss strategies to study changes in the brain and bodily fluids that precede clinical AD, focusing in particular on genetic at-risk individuals, who might be suitable candidates for secondary prevention trials.

Decompressive craniectomy (DC)—a surgical procedure that involves removal of part of the skull—has been used for many years in the management of patients with brain oedema and/or intracranial hypertension; however, the risk of post-surgery disability has raised important ethical issues. Here, Kolias et al. outline the history of DC, and review current considerations and evidence with regard to the use of this procedure in stroke, traumatic brain injury and other indications. The direction of future studies of DC is also discussed.

Daclizumab is a humanized monoclonal antibody that targets the IL-2 receptor α chain, and has shown promise as a novel treatment for multiple sclerosis (MS). Here, Wiendl and Gross provide an overview of clinical experience with daclizumab in MS, including results from phase II trials. They also discuss the putative mechanisms of action of this drug in MS pathogenesis, which involve dampening of early T-cell activation and upregulation of immunomodulatory natural killer cells.

The average age of the elderly population is increasing. In this Review, the authors examine the prevalence of dementia in the elderly population, and especially in the oldest old. Furthermore, they discuss the absence of dementia in the oldest old as a model of successful ageing, and the impact of genetic and environmental factors on various dementia phenotypes.

Primary CNS lymphoma (PCNSL) is a rare malignancy with an aggressive course, for which treatment has yet to be optimized. Here, Korfel and Schlegel discuss diagnostic approaches in patients with suspected PCNSL, and review the latest studies on new and more established therapeutic interventions. Ongoing issues—including the utility of whole-brain radiotherapy, and treatment of young, elderly and immunocompromised patients—are also considered.

This Review focuses on the growing area of telemedicine in the diagnosis and treatment of patients with acute stroke who are geographically remote from primary care centres. Hess and Audebert discuss telemedicine as a means to improve the availability of care for stroke patients, and the financial implications of this approach. Furthermore they highlight technological advances that might help to overcome barriers to the wider application of telemedicine in acute stroke care.

Susac syndrome is an important differential diagnosis in many neurological disorders, but our understanding of this rare disease has largely been limited to reports of single cases and small case series. In this article, Dörr and colleagues review all reported cases of Susac syndrome to provide a comprehensive overview of demographic, clinical and diagnostic data on this disorder. On the basis of their findings, Dörr et al. make recommendations for diagnosis and management of individuals with suspected Susac syndrome.

Neurological diseases that result from an underlying genetic mutation or from acquired genetic and/or epigenetic changes are prevalent in the population, and might be amenable to gene therapy. In this Review, Simonato et al. discuss new developments in gene therapy vector design and delivery for the treatment of neurological diseases, including sensorineural disorders, Parkinson disease and epilepsy. The authors also outline the most promising therapeutic approaches to date.

In patients with Parkinson disease (PD), the motor response to dopamine replacement therapy comprises an acute improvement in motor function, followed by the 'long-duration response' (LDR), in which motor improvements develop over weeks. Kang and colleagues review evidence to suggest that the LDR involves dopamine-dependent changes in corticostriatal plasticity, and discuss the implications of this framework for clinical management of PD. The authors argue that aberrant plasticity contributes to motor fluctuations during chronic dopamine replacement, and could be a novel therapeutic target for patients with PD or other basal ganglia disorders.

MicroRNAs (miRNAs) are short, single-stranded RNA molecules that inhibit translation of target mRNAs, and are key regulators of molecular and cellular responses in development, health and disease. A role for miRNAs in the regulation of pathology of CNS injuries has recently emerged, and in this Review, Bhalala et al. discuss findings from miRNA microarray studies in stroke, traumatic brain injury and spinal cord injury. They highlight how improved understanding of miRNA changes following CNS injuries can inform novel treatment strategies for these pathologies.

Traumatic brain injury (TBI) can occur as a single severe cranial impact or as repetitive concussions, and commonly affects professional athletes in contact sports and soldiers exposed to explosions. DeKosky and colleagues describe the distinct pathological changes accompanying each type of TBI, and characteristics of the resultant neuropathology, which frequently involves amyloid-β and tau aggregates. Potential biomarkers of TBI-induced damage are also outlined.

Tumours of the spinal cord are associated with high morbidity but, owing to the rarity of such tumours, our understanding of the biology of these lesions is limited. In this Review, Zadnik et al. summarize current knowledge on the demographics, genetics and treatment of the most common spinal cord tumours—namely, ependymomas, astrocytomas, haemangioblastomas and meningiomas—and highlight how recent advances in genetic studies are informing research to develop novel therapeutic approaches.

Cerebrospinal fluid (CSF) investigation should be routinely performed in patients with a first clinical event that is suggestive of multiple sclerosis (MS). This Review highlights the value of existing CSF biomarkers in eliminating potential differential diagnoses for MS and understanding the underlying pathophysiology of this condition. The authors also discuss the potential for novel biomarkers that could be used in prognosis.

Traumatic brain injuries (TBIs) sustained by athletes in contact–collision sports can cause long-term neurological complications. In recent years, cases of chronic traumatic encephalopathy—a neurodegenerative sequela of repetitive TBI—in retired boxers and American football players have been highly publicized. Here, Barry Jordan reviews the spectrum of sport-related brain injuries, and outlines the need for appropriate detection and management of both acute and chronic TBIs in athletes.

The link between traumatic brain injury and dementia has long been recognized, and has gained additional prominence through recent high-profile reports of chronic traumatic encephalopathy (CTE) in athletes exposed to repetitive head injury. In this Review, Smith et al. outline the neuropathological features of CTE that are thought to contribute to cognitive impairment, and discuss the work that remains to be done to define CTE as a distinct disease entity.

Around 25% of patients with subarachnoid haemorrhage (SAH) experience deterioration in the days following stroke, often as a result of delayed cerebral ischaemia (DCI). These deficits have been principally attributed to cerebral vasospasm, but recent studies suggest a role for dysfunction of cerebral autoregulation in post-SAH DCI. Budohoski et al. discuss recent findings on cerebral autoregulation, and present an overview of the pathophysiology and stages of autoregulatory impairment that occur following SAH.