The Genetics of Dementia With Lewy Bodies: What Are We Missing?
Meeus and colleaguesArticle provide a comprehensive overview of the current studies on dementia with Lewy bodies heritability, genetic etiology, and genetic heterogeneity. They conclude with a critical discussion of the missing heritability in dementia with Lewy bodies.
Cellular Immune Suppression in Paraneoplastic Neurologic Syndromes Targeting Intracellular Antigens
Orange et alArticle evaluate the short-term use of a combination of prednisone and tacrolimus for acute neurologic worsening in paraneoplastic neurologic disorder (PND) in which intracellular antigens are targeted. They report that a short course of prednisone and tacrolimus to target central nervous system T cells in patients with PND with acute neurologic decline in which intracellular antigens are targeted was well tolerated and warrants further study.
Kaplan-Meier survival curves. The dotted lines indicate 95% confidence intervals; the tick marks, censored patients; and the solid line, the survival curve. A, From time of diagnosis of paraneoplastic neurologic disorder. B, From start time of tacrolimus treatment.
Link Between Pain and Olfaction in an Inherited Sodium Channelopathy
Zufall et alArticle report that the voltage-gated sodium channel Nav1.7 plays a role in the human sense of smell and in the perception of pain. They review possible links between these sensory functions and sodium channelopathy.
Human Aquaporin 4281-300 Is the Immunodominant Linear Determinant in the Context of HLA-DRB1*03:01
Arellano and colleaguesArticle identify immunodominant linear determinants of human aquaporin 4 (hAQP4). They report that hAQP4281-330 is the dominant linear immunogenic determinant of hAQP4 in the context of HLA-DRB1*03:01. Within hAQP4281-330 are 2 dominant immunogenic determinants that induce differential TH phenotypes. hAQP4 determinants identified in this study can serve as diagnostic biomarkers in patients with neuromyelitis optica and may facilitate the monitoring of treatment responses to pharmacotherapies. Editorial perspective is provided by Carsten Korth, MD, PhDArticle.
Increased Cerebral Metabolism After 1 Year of Deep Brain Stimulation in Alzheimer Disease
Smith and colleaguesArticle test the hypotheses that deep brain stimulation (DBS) would increase cerebral glucose metabolism in cortical and hippocampal circuits and that increased metabolism would be correlated with better clinical outcomes. They found that the persistent cortical metabolic increases after 1 year of DBS were associated with better clinical outcomes in this patient sample and are greater in magnitude and more extensive in the effects on cortical circuitry compared with the effects reported for pharmacotherapy over 1 year in Alzheimer disease.
Frontotemporal Dementia in a Brazilian Kindred With the C9orf72 Mutation
Takada et alArticle describe the clinical features of a Brazilian kindred with C9orf72 frontotemporal dementia–amyotrophic lateral sclerosis and compare them with other described families with C9orf72 and frontotemporal dementia–amyotrophic lateral sclerosis–causing mutations. Behavioral variant frontotemporal dementia due to C9orf72 expansion displays some phenotypic heterogeneity and may be associated with hallucinations, parkinsonism, focal dystonia, and posterior brain atrophy. Personality changes may precede the diagnosis of dementia by many years and may be a distinguishing feature of this mutation.
C9ORF72 Repeat Expansion in Amyotrophic Lateral Sclerosis in the Kii Peninsula of Japan
Ishiura and colleaguesArticle delineate the molecular basis of amyotrophic lateral sclerosis (ALS) in the Kii peninsula of Japan. They analyzed hexanucleotide repeat expansion in the chromosome 9 open reading frame 72 (C9ORF72) gene, which has recently been identified as a frequent cause of ALS and frontotemporal dementia in the white population. They report that the repeat expansion partly accounts for the high prevalence of ALS in the Kii peninsula.
C9orf72 Hexanucleotide Repeat Expansions as the Causative Mutation for Chromosome 9p21–Linked Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
Daoud et alArticle assess the presence of a large hexanucleotide repeat expansion in the first intron of the C9orf72 gene identified as the genetic cause of chromosome 9p21–linked amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD) in 4 unrelated families with a conclusive linkage to c9ALS/FTD. Their findings further confirm the C9orf72 hexanucleotide repeat expansion as the causative mutation for c9ALS/FTD and strengthen the hypothesis that ALS and FTD belong to the same disease spectrum.
Characterization of a Family With c9FTD/ALS Associated With the GGGGCC Repeat Expansion in C9ORF72
Savica and colleaguesArticle characterize the antemortem characteristics of a family with chromosome 9p21–linked frontotemporal dementia and amyotrophic lateral sclerosis (c9FTD/ALS) associated with the GGGGCC repeat expansion in C9ORF72.Their report highlights the clinical and neuroimaging characteristics of a family with c9FTD/ALS. Further studies are needed to better understand the phenotypical variability and the cliniconeuroimaging-neuropathologic correlations.
Diabetes, Glucose Control, and 9-Year Cognitive Decline Among Older Adults Without Dementia
Yaffe et alArticle determine if prevalent and incident diabetes mellitus (DM) increase risk of cognitive decline and if, among elderly adults with DM, poor glucose control is related to worse cognitive performance. They note that, among well-functioning older adults, DM and poor glucose control among those with DM are associated with worse cognitive function and greater decline. This suggests that severity of DM may contribute to accelerated cognitive aging.
Epidemiology of Neuromyelitis Optica in the United States: A Multicenter Analysis
Mealy and colleaguesArticle develop a national multicenter neuromyelitis optica (NMO) clinical consortium and report initial demographic, clinical, and radiographic features of a cohort of patients with NMO and NMO spectrum disorder in the United States. This network establishes a foundation for determining disease prevalence, translational research, and clinical trials.
Distinct Patterns of Antiamyloid-β Antibodies in Typical and Atypical Alzheimer Disease
Dorothée et alArticle compare serum antiamyloid-β (Aβ) antibodies in typical and atypical Alzheimer disease (AD). They report that serum anti-Aβ IgG1 and IgG3 antibodies differ between distinct forms of AD. Its significance is discussed for possible implications as immune effectors in the specific pathophysiology of AD variants.
Association of Cerebral Microbleeds in Acute Ischemic Stroke With High Serum Levels of Vascular Endothelial Growth Factor
Dassan and colleaguesArticle determine whether vascular endothelial growth factor (VEGF) levels are associated with the presence of cerebral microbleeds (CMBs) in patients after acute ischemic stroke. Their data indicate that an increase in vascular permeability secondary to a raised VEGF level may have a role in the genesis of CMBs in patients with acute ischemic stroke.