News & Views in 2012

Anaplastic oligodendroglial tumours are chemosensitive tumours—a fact that has been known for almost 25 years. The role and optimal timing of chemotherapy, however, has remained a subject of debate. Long-term results of two phase III trials now show that, in patients with 1p19q-codeleted tumours, early chemotherapy increases overall survival.

Differential diagnosis of Creutzfeldt–Jakob disease (CJD) versus other—sometimes treatable—neurological disorders is challenging, owing in part to uncertainty about the utility of recommended diagnostic tools. Two recent studies have addressed the reliability of cerebrospinal fluid biomarkers in identification of patients with sporadic CJD among clinically suspected cases.

Several oral drugs have been developed in recent years for treatment of relapsing–remitting multiple sclerosis. Two large phase III trials have now clearly demonstrated the clinical efficacy and good safety profile of oral dimethyl fumarate (BG12)—an anti-inflammatory and cytoprotective agent—in patients with this disease.

Controversy exists over the best treatment option in elderly patients with glioblastoma. A recent study in glioblastoma patients who were over 60 years of age found improved survival rates with temozolomide chemotherapy compared with radiotherapy, and confirmed the validity of MGMT methylation status for prediction of benefit from temozolomide treatment.

Three recent phase III trials have shown that adjunctive treatment with perampanel—a first-in-class, noncompetitive AMPA antagonist—decreases seizure frequency in patients with refractory focal epilepsy. Although the introduction of perampanel offers more treatment choice for epilepsy, whether it brings urgently needed clinical benefit over existing drugs remains to be addressed.

Nearly 40% of ischaemic strokes remain cryptogenic when no clear aetiology is identified after a thorough initial investigation. Two recent articles in Stroke described extended arrhythmia monitoring modalities to reveal paroxysmal atrial fibrillation in patients with ischaemic stroke, with implications for decisions regarding anticoagulation.

New EFNS–ENS guidelines provide a broad and comprehensive overview of the literature and key recommendations regarding treatment and diagnosis across a vast range of conditions associated with dementia, with the exception of Alzheimer disease, which was deliberately excluded. Although excellent, the breadth and brevity of the guidelines lead to some important omissions.

In a recent trial investigating the effectiveness of speech and language therapy versus a control intervention in poststroke aphasia, patient outcome improved equally in both groups. However, flaws in the study relating to design of the control intervention, inadequate therapy 'dose', and the interpretation of null results should be highlighted.

Whether dominantly inherited variants of Alzheimer disease (AD) and 'sporadic' forms exhibit similar pathophysiological and biomarker signatures remains unresolved. A landmark study has proposed a biomarker progression model of dominantly inherited AD, but a complex systems biology and physiology approach is required to translate these findings to sporadic disease.

Multiple sclerosis is an inflammatory, demyelinating disease in which antigens of the myelin sheath have been considered the autoimmune target. A recent study suggests that the potassium channel KIR4.1 is another potential autoantigen in some patients with multiple sclerosis, and might also be a target in other demyelinating diseases.

Controversy exists over the treatment of brain arteriovenous malformations. A recent study suggests that, irrespective of clinical presentation, invasive treatment has no benefit over conservative management with regard to risk of seizure. Whether eradication is superior to medical management alone for those with seizures, headache and/or haemorrhage remains unsettled.

The understanding and treatment of medulloblastoma, the most common childhood malignant brain tumour, is rapidly evolving. Three complementary deep-sequencing studies that were recently published in Nature add to our knowledge of this disease, further refine risk stratification, and identify potential druggable targets.

Natural history of multiple sclerosis includes phases of relapse, remission and insidious progression. New data show that sustained improvements in disease, defined by reductions in EDSS scores, occur independent of relapses almost half as frequently as disease worsening. This finding might facilitate research into the biological processes involved in disease improvement.

The introduction of recombinant tissue-type plasminogen activator (tPA) revolutionized stroke treatment, but experimental studies have suggested potential toxic effects of this molecule on various components of the CNS. Two new studies have added further insight into the complex CNS effects of tPA following traumatic brain injury and brain ischaemia.

Understanding how genetic variation can confer susceptibility to neurological disease is an urgent priority. A new gene-expression study has explored the relationship between DNA sequence variation at the microtubule-associated protein tau (MAPT) locus and MAPT expression in the brain, providing an exciting new paradigm for the field.

High platelet reactivity persists in many patients receiving antiplatelet therapy for secondary prevention of ischaemic stroke. Patient-tailored antiplatelet therapy, guided by platelet function tests, is an appealing approach for prevention of recurrent vascular events. However, a recent study has demonstrated that this strategy is associated with worse clinical outcomes.

Megalencephaly syndromes are a spectrum of severe developmental neurological disorders associated with brain overgrowth. Two recent studies highlight the pathogenic role of somatic mutations in genes of the mTOR signalling pathway in the brains of patients with these conditions, providing hope for development of new treatments.

One of the main challenges associated with diagnosis of Alzheimer disease (AD) is the identification and validation of blood-based biomarkers. Three recent studies describe different approaches to blood-based biomarker research in AD, and provide hope for a simple, minimally invasive means of diagnosis.

Over the past two decades, trials of citicoline for treatment of acute stroke have produced conflicting results. A recent large clinical trial of citicoline in acute stroke suggests a lack of efficacy of this therapy, seemingly signalling the end to the citicoline saga.

An evidence-based update to the 2004 guidelines for the treatment of infantile spasms has recently been published. Important new recommendations include use of low-dose adrenocorticotropic hormone (ACTH) over high-dose ACTH or vigabatrin. A paucity of data, however, leaves several key questions unanswered.