Mullen and Scheffer Article provide an elegant update of the genetics of sodium channelopathies and epilepsy. Recently-developed animal models of sodium channel–gene SCN1A mutants recapitulate the human disease. Their review illustrates the key role basic science plays in the development of targeted novel therapies and that ultimately will lead to the prevention of these serious disorders.
Yokota et al Article provide new insights into antisense oligonucleotides, short nucleic acid sequences designed for use as small-molecule drugs that bind to specific mRNA sequences and alter mRNA-splicing patterns or inhibit protein synthesis. Impressive preclinical and clinical data using antisense have been shown to increase dystrophin production in Duchenne muscular dystrophy. Clearly, this technology will have a major effect as therapy for genetic neurological disease in the near future.
Chiu et al Article investigate the heterogeneity in magnetic resonance imaging patterns of response to interferon beta in patients with multiple sclerosis. They report multiple magnetic resonance imaging evaluations showing that only about half of patients treated with interferon beta achieve and maintain a full response to the drug over time. Editorial perspective is provided by Paul S. Giacomini, MD, FRCP(C), Douglas L. Arnold, MD, Amit Bar-Or, MD, FRCP(C), MSc, and Jack P. Antel, MD.Article
Moll and colleagues Article have compared leukocyte accumulation with expression of the chemokine receptor/ligand pair CXCR4/CXCL12 in MRI-defined regions of interest (ROIs) in the brains of patients with multiple sclerosis (MS). Of note, inflammatory leukocyte accumulation was not increased in myelinated MS ROIs with abnormal T2 signal compared with normal-appearing white matter. However, robust expression of chemokine activity on inflammatory elements in MS lesions highlights a role of this chemokine/receptor pair in brain inflammation.
Wiley and colleagues Article, using two carbon 11 ([11C])–labeled positron emission tomographic imaging agents, Pittsburgh compound B (PiB) and (R)-PK11195, examined the relationship between amyloid deposition and microglial activation in different stages of Alzheimer disease (AD). They show that subjects with probable AD had greater levels of [11C]PiB retention than controls, while patients with mild cognitive impairment spanned a range from controllike to AD-like levels of [11C]PiB retention. They observed no differences in brain [11C](R)-PK11195 retention when subjects were grouped by clinical diagnosis or the presence of β-amyloid pathology, as indicated by analysis of [11C]PiB retention.
Carbon 11–labeled ([11C]) Pittsburgh Compound B (PiB) standardized uptake value ratio over 90 minutes (SUVR90) outcome measures corrected for cerebral atrophy for the mesial temporal cortex (MTC), sensorimotor cortex (SMC), frontal cortex (FRT), parietal cortex (PAR), and posterior cingulate or precuneus region (PRC). Data are classified by clinical diagnosis (control, mild cognitive impairment [MCI], or Alzheimer disease [AD]) (A) and [11C]PiB retention (B). Indices of [11C]PiB retention in patients with AD show significantly higher values relative to control subjects in cortical regions (P < .05). Also, when classified on the basis of amyloid pathological findings (PiB positive or PiB negative), PiB-positive subjects showed indices of retention that were approximately 2-fold higher than PiB-negative subjects (P < .01) in regions where β-amyloid pathological findings are expected.
Gorman et al Article find that relapses are more frequent in patients with pediatric-onset compared with adult-onset multiple sclerosis. This finding suggests that patients with pediatric-onset multiple sclerosis experience a more inflammatory disease course than adult-onset patients.
Wilson et al Article provide evidence that onset of chronic neurological illness in adolescence influences the development of adult personality traits. Further, they find a relationship between personality and adjustment to chronic epilepsy.
Chamberlain and colleagues Article provide a comparison evaluating survival in 2 well-matched cohorts of patients with cytologically positive neoplastic meningitis presenting with or without independence in activities of daily living, as measured by Karnofsky performance status (KPS). They report that low KPS is a clinical variable that predicts for poor survival in patients with neoplastic meningitis. As a consequence, patients with low KPS may be best served by offering supportive care.
Patel et al Article report that nontraumatic subdural hematoma frequently accompanies primary lobar hemorrhage and is associated with a higher 30-day mortality rate. Rupture of a cerebral amyloid angiopathy–laden leptomeningeal vessel with extravasation into brain parenchyma and subdural space may be the pathogenic mechanism.
Kaufmann and colleagues Article have demonstrated that A3243G mutation carriers have multiple medical problems, suggesting that the A3243G mutation should be considered as an etiological factor in patients with multisystem clinical presentations or a family history compatible with matrilineal inheritance.
Pardini et al Article show more severe olfactory impairment for patients with corticobasal syndrome than previously reported. They find a significant relationship between formal olfactory recognition testing scores and specific cognitive domains. These findings could be very useful to differentiate patients with clinically frontotemporal-frontal variants from patients with corticobasal syndrome or other dementing and movement disorders.
De Vries and colleagues Article have broadened the clinical spectrum associated with SLC1A3 mutations to include milder manifestations of episodic ataxia without seizures or alternating hemiplegia. The severity of symptoms correlated with the extent of glutamate transporter dysfunction.
Ibáñez et al Article show that α-synuclein gene (SNCA) rearrangements may be more frequent than point mutations in autosomal dominant Parkinson disease. Their results indicate that the phenotype associated with α-synuclein multiplications correlates with the number of copies of the gene and provides the first insight into the mechanisms underlying SNCA multiplication.
Stanton et al Article have used diffusion tensor imaging as a measure of axonal pathology in vivo in amyotrophic lateral sclerosis (ALS), comparing a homogeneous form of familial ALS with sporadic ALS. In vivo diffusion tensor imaging measures demonstrate differences in white matter degeneration between sporadic ALS and a unique familial form of the disease, indicating that genotype influences the distribution of cerebral pathology in ALS.
This Month in Archives of Neurology. Arch Neurol. 2009;66(1):17-18. doi:10.1001/archneurol.2008.543