Reviews & Analysis

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.

Drugs acting on the cholinergic system can improve or worsen cognitive abilities, and their effects are particularly pronounced in frail elderly individuals and patients with Alzheimer disease. Guidelines are urgently needed on the judicious use of cholinergic drugs.

Sialorrhea is a common and often debilitating, socially isolating and embarrassing symptom for patients with Parkinson disease (PD). The treatment of sialorrhea involves the management of saliva production, and is complicated in this disease by the risk of aspiration. Two novel approaches to the treatment of this symptom in PD have recently been published.

Patients with relapsing–remitting multiple sclerosis have been shown to benefit from disease-modifying treatments over prolonged periods. More focus should now be placed on monitoring the long-term evolution of this disease (making use of tools such as MRI), alongside the patients' response and adherence to such treatments.

A new study indicates that single-pulse transcranial magnetic stimulation can provide substantial long-lasting pain relief in patients with migraine with aura. The findings suggest that non-pharmacological therapies could be used to successfully abort migraine attacks in patients who find that drug therapies do not adequately control migraine symptoms.

A meta-analysis of results from the Oxford Vascular Study indicates that rates of mortality associated with subarachnoid hemorrhage have decreased over the past 30 years. The study does not, however, address whether day-to-day functioning and quality of life in subarachnoid hemorrhage survivors have improved over the same time period.

A randomized, double-blind clinical trial that compared three widely used anticonvulsants for childhood absence epilepsy established that ethosuximide was the most appropriate first-line therapy for this condition. The study provides guidance for the treatment of this common childhood epilepsy where evidence-based recommendations have previously been lacking.

Dramatic advances have been made in the treatment of motor dysfunction in both the early and late phases of Parkinson disease. Effective therapies for the nonmotor symptoms of this disease, however, remain a major unmet clinical need. A recent study has highlighted the dearth of clinical trials for some of these symptoms.

For the first time, medical sequencing has been successfully performed at the genome level to identify the causative gene in an individual with autosomal recessive Charcot–Marie–Tooth disease. The results of sequencing a proband with this condition highlight some of the opportunities and challenges of this seemingly ultimate approach to human genetics research and diagnostics.

Proteins linked to neurodegenerative diseases can potentially be used as biomarkers. A study now shows that after accounting for confounding variables such as age and blood contamination, cerebrospinal fluid levels of α-synuclein and DJ1 are substantially reduced in patients with Parkinson disease compared with healthy controls or individuals with Alzheimer disease.

To maximize the benefits of thrombolytic therapy at the population level, identifying which stroke patients are most likely to respond positively to this treatment is vital. The EPITHET Investigators propose specific diffusion-weighted and perfusion-weighted MRI lesion volume criteria that could be used for patient selection.

Hereditary eye diseases can feature extraocular neurological complications, although such additional phenotypes can go undetected when a patient's visual defect is dramatic. A consortium has found that extraocular neurological phenotypes are common in patients with OPA1 mutation-related autosomal dominant optic atrophy, occurring in one-fifth of all such individuals.

Analysis of two recombinant tissue plasminogen activator (rtPA) trials by means of the disability-adjusted life year metric has provided readily understandable data on the benefits of rtPA therapy in acute ischemic stroke. Approximately one-third of patients treated with rtPA could gain more than 4 years of healthy life, which is twice that previously estimated.

The burden of cerebrovascular disease is thought to be greater than current official estimates. A new systematic review shows that a history of stroke is associated with an increased risk of incident dementia in the elderly. The findings also highlight the confusion in the classification of dementia and the need for more recognition of vascular-related cognitive disorders.

Classification of glioblastomas into various molecular entities is required for the successful application of targeted therapeutics and personalized cancer therapy. Analyses of gene expression, genomic mutations and DNA copy number identified four molecular subtypes among histopathologically indistinguishable glioblastomas. This classification suggests the existence of distinct paths of tumor cell origin and variation in therapeutic sensitivity.

Two genome-wide association studies have independently identified genetic risk factors for Parkinson disease (PD). One study, conducted in individuals of European ancestry, provides further evidence for an association between PD risk and the genes SNCA and MAPT. The other study, conducted in a Japanese series, identified two novel loci that are associated with PD risk.

The dramatic increase in survival of extremely premature infants has been associated with a growing population of individuals with neurodevelopmental disabilities. To date, clinical trials of neuroprotective agents in preterm infants have been limited, but new data suggest that erythropoietin might have important neuroprotective effects in these vulnerable infants.

The role of hyperlipidemia as a risk factor for stroke is unclear. A new retrospective study has examined the relationship between a history of hyperlipidemia and MRI-defined white matter hyperintensities in patients with acute ischemic stroke. The results indicate that hyperlipidemia might have a protective role against cerebral small-vessel disease.

Evidence suggests that both anxiety and depression might have pathophysiological links with Parkinson disease (PD), as these mood disorders are more prevalent in individuals with PD than in patients with other chronic conditions. A new study reports that depression and anxiety are associated with different patterns of PD-related factors, suggesting divergence between the underlying mechanisms.