Nature reviews. Neurology
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Nature reviews. Neurology · Nov 2014
ReviewClassifying neurocognitive disorders: the DSM-5 approach.
Neurocognitive disorders--including delirium, mild cognitive impairment and dementia--are characterized by decline from a previously attained level of cognitive functioning. These disorders have diverse clinical characteristics and aetiologies, with Alzheimer disease, cerebrovascular disease, Lewy body disease, frontotemporal degeneration, traumatic brain injury, infections, and alcohol abuse representing common causes. This diversity is reflected by the variety of approaches to classifying these disorders, with separate groups determining criteria for each disorder on the basis of aetiology. ⋯ The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) provides a common framework for the diagnosis of neurocognitive disorders, first by describing the main cognitive syndromes, and then defining criteria to delineate specific aetiological subtypes of mild and major neurocognitive disorders. The DSM-5 approach builds on the expectation that clinicians and research groups will welcome a common language to deal with the neurocognitive disorders. As the use of these criteria becomes more widespread, a common international classification for these disorders could emerge for the first time, thus promoting efficient communication among clinicians and researchers.
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Nature reviews. Neurology · Nov 2014
ReviewMaternal immune activation and abnormal brain development across CNS disorders.
Epidemiological studies have shown a clear association between maternal infection and schizophrenia or autism in the progeny. Animal models have revealed maternal immune activation (mIA) to be a profound risk factor for neurochemical and behavioural abnormalities in the offspring. Microglial priming has been proposed as a major consequence of mIA, and represents a critical link in a causal chain that leads to the wide spectrum of neuronal dysfunctions and behavioural phenotypes observed in the juvenile, adult or aged offspring. ⋯ Here, we summarize and critically review the emerging evidence that mIA is a shared environmental risk factor across CNS disorders that varies as a function of interactions between genetic and additional environmental factors. We also review ongoing clinical trials targeting immune pathways affected by mIA that may play a part in disease manifestation. In addition, future directions and outstanding questions are discussed, including potential symptomatic, disease-modifying and preventive treatment strategies.
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Nature reviews. Neurology · Nov 2014
ReviewThe phenotypic variability of amyotrophic lateral sclerosis.
Classic textbook neurology teaches that amyotrophic lateral sclerosis (ALS) is a degenerative disease that selectively affects upper and lower motor neurons and is fatal 3-5 years after onset--a description which suggests that the clinical presentation of ALS is very homogenous. However, clinical and postmortem observations, as well as genetic studies, demonstrate that there is considerable variability in the phenotypic expression of ALS. ⋯ Furthermore, we discuss some unusual clinical characteristics regarding presentation, age at onset and disease progression. Finally, we address the importance of this variability for understanding the pathogenesis of ALS and for the development of therapeutic strategies.