Acute flaccid myelitis:cause, diagnosis, and management

Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of MM have occurred across multiple global regions since 2012, and the disease appears to be caused by non-polio enterovirus infection, posing a major public health challenge. The clinical presentation of flaccid and often profound muscle weakness (which can invoke respiratory failure and other critical complications) can mimic several other acute neurological illnesses. There is no single sensitive and specific test for MM, and the diagnosis relies on identification of several important clinical, neuroimaging, and cerebrospinal fluid characteristics. Following the acute phase of AFM, patients typically have substantial residual disability and unique long-term rehabilitation needs. In this Review we describe the epidemiology, clinical features, course, and outcomes of AFM to help to guide diagnosis, management, and rehabilitation. Future research directions include further studies evaluating host and pathogen factors, including investigations into genetic, viral, and immunological features of affected patients, host-virus interactions, and investigations of targeted therapeutic approaches to improve the long-term outcomes in this population

Illustrations of the Afferent Visual Pathway and Concepts Surrounding Trans-Synaptic Neuroaxonal Degeneration in the Visual Pathway in Multiple Sclerosis

Image 1 title: Functionally-eloquent organization of the afferent visual pathway; Image 1 description: The afferent visual pathway is a sensory pathway comprised of 3 neurons. The 1st order neurons are the shortest neurons in the pathway and are entirely unmyelinated. The cell bodies of the 1st order neurons lie in the retinal inner nuclear layer (INL), with the axons travelling to the retinal ganglion cell layer (GCL) where they synapse with the cell bodies of the 2nd order neurons. The INL and GCL are highlighted here on a spectral domain optical coherence tomography image of a healthy retina (Spectralis HD-OCT, Heidelberg, Germany). The axons of the 2nd order neuron pass through the peripapillary retinal nerve fiber layer and coalesce to make up the optic nerve, becoming myelinated after they pass through lamina cribrosa. Axons from the nasal half of the retina are organized within the optic nerve and cross over to the contralateral cerebral hemisphere at the optic chiasm, while axons from the temporal half of the retina remain uncrossed and continue their path within the ipsilateral cerebral hemisphere. After traversing the optic tracts, the axons of the 2nd order neurons synapse with the cell bodies of the 3rd order neurons in the lateral geniculate nucleus of the thalamus, with each thalamus receiving signals from the right and left eye, due to the crossed and uncrossed nature of the pathway. The axons of the 3rd order neurons then travel within the optic radiations to reach the primary visual cortex of the occipital lobe.; ; Image 2 title: Neuroaxonal degeneration in the afferent visual pathway following axonal injury; Image 2 description: This figure illustrates the potential patterns of neuroaxonal degeneration that may occur after injury to an axon in the afferent visual pathway (e.g. with optic neuritis), or in other synaptically-connected pathways. Following axonal injury, the affected neuron may degenerate in both an anterograde (‘dying forward') or retrograde (‘dying back') direction. Following degeneration of the injured neuron, neurodegeneration may proceed trans-synaptically to the other neurons in the chain, again in an anterograde or retrograde direction, resulting in loss of distant uninjured but synaptically-connected neurons.; ; Image 3 title: Patterns of trans-synaptic degeneration in the afferent visual pathway in multiple sclerosis; Image 3 description: The afferent visual pathway is a functionally eloquent sensory pathway made up of 3 neurons, travelling from the retina to the primary visual cortex of the occipital lobe. The axons of the 2nd order neurons (travelling from the retinal ganglion cell layer through the optic nerve and optic tracts to the thalami) are highly-organized, with the axons from the nasal half of the retina crossing over to the contralateral cerebral hemisphere within the optic chiasm, while the axons from the temporal half of the retina remain uncrossed and continue their path within the ipsilateral cerebral hemisphere. The crossed and uncrossed nature of the pathway means that each thalamus and visual cortex receives inputs from the right and left eye in a homonymous pattern. In optic neuritis, injury to the axons of the 2nd order neurons (prior to the optic chiasm) can result in anterograde degeneration of affected axons, a process which may then proceed trans-synaptically, resulting in degeneration of the 3rd order neurons travelling from both thalami to both primary visual cortices. Neuroaxonal degeneration after optic neuritis may also proceed in the retrograde direction, resulting in loss of cell bodies in the ipsilateral retinal ganglion cell layer (GCL), and potentially trans-synaptically to the 1st order neurons contained in the ipsilateral retinal inner nuclear layer (INL). On the other hand, if a demyelinating lesion causes axonal injury to the 3rd order neurons (e.g. within the optic radiations), anterograde neuroaxonal degeneration may result in atrophy of the ipsilateral visual cortex, while retrograde degeneration may proceed to the ipsilateral thalamus, and potentially trans-synaptically to the highly-organized crossed and uncrossed 2nd order neurons, resulting in a homonymous pattern of atrophy of the retinal ganglion cell layer (and possibly even trans-synaptically again to the 1st order neurons within the retinal inner nuclear layer)

Chorea–Acanthocytosis and the Huntington Disease Allele in an Irish Family

The presence of peripheral blood film acanthocytes can help narrow the differential diagnosis of a familial choreiform disorder. Acanthocytosis is associated with chorea–acanthocytosis (ChAc), McLeod syndrome, pantothenate kinase-associated neurodegeneration (PKAN), and Huntington’s disease-like 2 (HDL-2). Huntington disease (HD) can present at a similar age with a similar phenotype, but without acanthocytosis. We report the cases of three adult siblings with genetically confirmed ChAc, and discuss the unusual finding of a co-existing abnormal HD allele (CAG repeat expansion in the range of reduced penetrance) in two of these siblings

Acute flaccid myelitis: cause, diagnosis, and management

Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of AFM have occurred across multiple global regions since 2012, and the disease appears to be caused by non-polio enterovirus infection, posing a major public health challenge. The clinical presentation of flaccid and often profound muscle weakness (which can invoke respiratory failure and other critical complications) can mimic several other acute neurological illnesses. There is no single sensitive and specific test for AFM, and the diagnosis relies on identification of several important clinical, neuroimaging, and cerebrospinal fluid characteristics. Following the acute phase of AFM, patients typically have substantial residual disability and unique long-term rehabilitation needs. In this Review we describe the epidemiology, clinical features, course, and outcomes of AFM to help to guide diagnosis, management, and rehabilitation. Future research directions include further studies evaluating host and pathogen factors, including investigations into genetic, viral, and immunological features of affected patients, host-virus interactions, and investigations of targeted therapeutic approaches to improve the long-term outcomes in this population

Phylogenomics and the rise of the angiosperms.

Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods1,2. A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome3,4. Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins5-7. However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes8. This 15-fold increase in genus-level sampling relative to comparable nuclear studies9 provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade

Phylogenomics and the rise of the angiosperms

International audienceAngiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods 1,2 . A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome 3,4 . Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins 5–7 . However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes 8 . This 15-fold increase in genus-level sampling relative to comparable nuclear studies 9 provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade