Spinal Muscular Atrophy: A Timely Review
Kolb and KisselArticle review the relentless progress during the past 15 years in the understanding of the molecular genetics and pathophysiology of spinal muscular atrophy (SMA) that has resulted in a unique opportunity for rational, effective therapeutic trials. The goal of SMA therapy is to increase the expression levels of the SMN protein in the correct cells at the right time. With this target in sight, investigators can now effectively screen potential therapies in vitro, test them in accurate, reliable animal models, move promising agents forward to clinical trials, and accurately diagnose patients at an early or presymptomatic stage of disease. A major challenge for the SMA community will be to prioritize and develop the most promising therapies in an efficient, timely, and safe manner with the guidance of the appropriate regulatory agencies. This review will take a historical perspective to highlight important milestones on the road to developing effective therapies for SMA.
Rett Syndrome: Exploring the Autism Link
PercyArticle explores the commonalities and differences between autism and Rett syndrome (RTT) at clinical and molecular levels with respect to current status and challenges for each, highlights recent findings from the Rare Disease Network Natural History study on RTT, and summarizes the broad range of phenotypes resulting from mutations in the methyl CpG binding protein 2 gene (MECP2), which is responsible for RTT in 95% of individuals with the disorder.
Lack of Evidence for the Efficacy of Memantine in Mild Alzheimer Disease
Schneider and colleaguesArticle assessed the clinical trials' evidence for memantine's efficacy in mild Alzheimer disease (AD). Despite its frequent off-label use, evidence is lacking for a benefit of memantine in mild AD, and there is meager evidence for its efficacy in moderate AD. Prospective trials are needed to further assess the potential for efficacy of memantine either alone or added to cholinesterase inhibitors in mild and moderate AD.
Medical School and Residency Influence on Choice of an Academic Career and Academic Productivity Among US Neurology Faculty
Campbell et alArticle evaluate the effectiveness of medical schools and neurology training programs in the United States by determining their contribution to academic neurology in terms of how many graduates choose academic careers and their respective influence on current medical knowledge through bibliometric analysis. Their retrospective, longitudinal cohort study examines through quantitative measures the academic productivity and rank of academic neurologists. Their results demonstrate that several training programs excel in producing a significantly higher proportion of academically active neurologists.
Reversible Cerebral Vasoconstriction Syndromes: Analysis of 139 Cases
Singhal and colleaguesArticle analyzed 139 patients with reversible cerebral vasoconstriction syndromes. They report that patients with reversible cerebral vasoconstriction syndromes have a unique set of clinical imaging features, with no significant differences between subgroups. Prospective studies are warranted to determine the effects of empirical treatment with calcium channel blockers and glucocorticoids. Editorial perspective is provided by Brian J. Anziska, MD, Christopher Dardis, MD, and Steven R. Levine, MDArticle.
Typical neuroimaging features of reversible cerebral vasoconstriction syndrome. A, Head computed tomography angiogram, sagittal maximum-intensity projection image, showing the classic “sausage on a string” appearance of both anterior cerebral arteries. B, Head computed tomography, axial image, showing subarachnoid hemorrhage overlying the right frontal lobe (vertical arrow).
Association and Expression Analyses With Single-Nucleotide Polymorphisms in TOMM40 in Alzheimer Disease
Cruchaga et alArticle attempt to replicate a recently reported association of APOE 3–TOMM40 haplotypes with risk and age at onset. Although they did not replicate the earlier association between the APOE 3–TOMM40 haplotypes and age at onset, they did observe that the polyT polymorphism is associated with risk of late-onset Alzheimer disease among APOE 33 homozygotes in a large case-control series but in the opposite direction as in the previous study. Additional studies in large samples are needed to confirm this association.
Association of Low Ejection Fraction With Impaired Verbal Memory in Older Patients With Heart Failure
Festa and colleaguesArticle investigate the relationships among age, memory, and left ventricular ejection fraction (EF) in patients with heart failure. They find that the effect of EF on memory differs by age such that older patients with lower EFs have significantly reduced verbal memory function.
Referring Patients for Deep Brain Stimulation: An Improving Practice
Katz et alArticle reviewed referral patterns to a large movement disorders center to investigate the current level of knowledge surrounding deep brain stimulation (DBS) candidacy. They report that, compared with findings in prior studies, the quality of DBS referrals has improved. The increase in referral of possible future candidates and poor candidates may reflect greater confidence in the procedure.
Deep Brain Stimulation in Benign Tremulous Parkinsonism
Savica and colleaguesArticle assess the clinical outcomes of patients with benign tremulous parkinsonism (BTP) who underwent deep brain stimulation (DBS) and to compare these clinical outcomes based on different surgical targets: thalamic nucleus ventralis intermedius (VIM) and subthalamic nucleus (STN). Their findings support the efficacy of DBS, with VIM and STN targets, in medically refractory BTP-related tremor. They point out, however, that further studies are needed to explore the long-term durability of response and to better compare the surgical targets.
Resting Tremor in Parkinson Disease: A Negative Predictor of Levodopa-Induced Dyskinesia
Kipfer et alArticle determine whether resting tremor as an initial manifestation of Parkinson disease (PD) negatively correlated with subsequent occurrence and severity of levodopa-induced dyskinesia (LID) and study the correlations between LID and other epidemiological factors (eg, age at onset of PD and duration of PD). They find that resting tremor as an initial manifestation of PD predicts a lower probability of developing LID under levodopa treatment.
The Dynamics of Cortical and Hippocampal Atrophy in Alzheimer Disease
Sabuncu and colleaguesArticle characterize rates of regional Alzheimer disease (AD)–specific brain atrophy across the presymptomatic, mild cognitive impairment, and dementia stages. They show that AD-specific cortical thinning and hippocampal volume loss are consistent with a sigmoidal pattern, with an acceleration phase during the early stages of the disease.
Ecology of Aging Human Brain
Sonnen et alArticle emphasize that Alzheimer disease, cerebral vascular brain injury, and isocortical Lewy body disease are the major contributors to dementia in the following community- and population-based studies: Adult Changes in Thought study (ACT), Honolulu-Asia Aging Study (HAAS), Nun Study (NS), and Oregon Brain Aging Study (OBAS). However, the prevalence of clinically silent forms of these diseases in cognitively normal (CN) adults is less clear. They evaluate 1672 brain autopsies from the ACT study, HAAS, NS, and OBAS, of which 424 met the criteria for CN. Their data show an individually varying complex convergence of subclinical diseases in the brain of older CN adults. Appreciating this ecology should help guide future biomarker and neuroimaging studies and clinical trials that focus on community- and population-based cohorts.
Differential Involvement of Optineurin in Amyotrophic Lateral Sclerosis With or Without SOD1 Mutations
Deng and colleaguesArticle determine whether optineurin-positive skeinlike inclusions are a common pathologic feature in amyotrophic lateral sclerosis (ALS), including SOD1 -linked ALS. Their data provide evidence that optineurin is involved in the pathogenesis of sporadic ALS and non- SOD1 familial ALS, thus supporting the hypothesis that these forms share a common pathway that is distinct from SOD1 -linked ALS.