Stüve and colleagues Article outline some of the pharmacological agents that have been developed and tested in the laboratory and successfully brought into clinical trials and through the regulatory approval process. Agents that are currently in development are discussed. They give examples of how clinical observations following the approval of particular drugs led to new discoveries regarding their mechanisms of action. Finally, they contemplate some of the challenges that lie ahead in drug development and how novel biomarkers and laboratory methods may help to overcome these challenges.
Qureshi and Mehler Article describe emerging evidence that implicates a spectrum of epigenetic processes in the pathophysiology of stroke. They describe conventional epigenetic mechanisms including DNA methylation, histone code modifications, nucleosome remodeling, and higher-order chromatin formation, and highlight the emerging roles each of these processes has in stroke pathobiology.
Muresan and colleagues Article have evaluated if very early neurological improvement (VENI) at the end of intravenous recombinant tissue plasminogen activator (rt-PA) perfusion in acute ischemic stroke may predict good outcome at 3 months. Of 120 patients with acute ischemic stroke who were treated with intravenous rt-PA, 22 patients (18.3%) had VENI after intravenous rt-PA. Favorable outcome was observed in 68.2% of patients with VENI and in 29.5% of patients with no VENI (P < .001). Thus, they show that VENI at the end of intravenous rt-PA perfusion in acute ischemic stroke independently predicts good outcome at 3 months.Editorial perspective is provided by José Biller, MD.Article
Rudick et al Article, in a phase 3 clinical trial of intramuscular interferon beta-1a, report that, compared with effects of treatment, baseline Expanded Disability Status Scale (EDSS) score, and number of on-study relapses, worsening from a baseline EDSS score of greater than 1.0 point lasting 6 months was the strongest predictor of clinically significant disability 8 years after randomization into the clinical trial.
Patients progressing to specific Expanded Disability Status Scale (EDSS) milestones at 8 years by treatment status.
Warner and colleagues Article have determined the spatial distribution of cortical and subcortical volume loss in patients with diffuse traumatic axonal injury to assess the relationship between regional atrophy and functional outcome. Decreases in volume were seen in several brain regions including the amygdala, hippocampus, thalamus, corpus callosum, putamen, precuneus, postcentral gyrus, paracentral lobule, and parietal and frontal cortices, while other regions such as the caudate and inferior temporal cortex were relatively resistant to atrophy. Traumatic axonal injury leads to substantial posttraumatic atrophy that is regionally selective rather than diffuse, and volume loss in certain regions may have prognostic value for functional recovery.
Sadleir and Scheffer Article have studied whether early electroencephalogram (EEG) or later sleep-deprived EEG has a higher yield of epileptiform and background abnormalities in children with new-onset seizures. Sleep-deprived and early EEG studies have a similar yield of epileptiform abnormalities. Background abnormalities are more frequent in early EEGs. At presentation, EEG in new-onset seizures supports an epilepsy diagnosis, with electroclinical syndromes diagnosed in 50% of children.
Mata and colleagues Article indicate that a functional repeat polymorphism in the SNCA promoter (REP1) conveys susceptibility to Parkinson disease (PD). There is also increasing evidence that single-nucleotide polymorphisms elsewhere in the gene are associated with risk. They sought to further explore the disease association, determine whether evidence of allelic heterogeneity exists, and examine the correlation between PD-associated variants and plasma α-synuclein levels. Their data suggest that 1 or more unidentified functional SNCA variants modify risk of PD and that the effect is larger than, and independent of, REP1. This variant(s), tagged by rs356219, might act by upregulating SNCA expression in a dose-dependent manner.
Brüggemann et al Article have determined clinical features and identified changes in brain structure and function in compound heterozygous and heterozygous ATP13A2 mutation carriers. They report that single ATP13A2 heterozygous mutations may be associated with clinical signs of parkinsonism and contribute to structural and functional brain changes.
Storandt and Morris Article have pointed out that the clinical diagnosis of Alzheimer disease is often based, at least in part, on poor cognitive test performance compared with normative values. They have examined the presence and extent of an ascertainment bias (omission of affected individuals) produced by such criteria when applied as early as possible in the course of the disease. They find that reliance on divergence from group normative values to determine initial cognitive decline caused by Alzheimer disease results in failure to include people in the initial symptomatic stage of the illness.
Carmichael and colleagues Article have evaluated relationships between magnetic resonance imaging–based measures of white matter hyperintensities, measured at baseline and longitudinally, and 1-year cognitive decline using a large convenience sample in a clinical trial design with a relatively mild profile of cardiovascular risk factors. They report that white matter hyperintensity volume predicts 1-year cognitive decline in a relatively healthy convenience sample that was similar to clinical trial samples, and therefore should be considered as a covariate of interest at baseline and longitudinally in future Alzheimer disease treatment trials.
Murray et al Article have investigated the effect that white matter hyperintensities detected on magnetic resonance imaging have on motor dysfunction and cognitive impairment in elderly subjects without dementia. They conclude that executive function is the primary cognitive domain affected by white matter hyperintensity burden.
This Month in Archives of Neurology. Arch Neurol. 2010;67(11):1303-1304. doi:10.1001/archneurol.2010.273