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Patients with ALS show highly correlated progression rates in left and right limb muscles.
ObjectiveAmyotrophic lateral sclerosis (ALS) progresses at different rates between patients, making clinical trial design difficult and dependent on large cohorts of patients. Currently, there are few data showing whether the left and right limbs progress at the same or different rates. This study addresses rates of decline in specific muscle groups of patients with ALS and assesses whether there is a relationship between left and right muscles in the same patient, regardless of overall progression.MethodsA large cohort of patients was used to assess decline in muscle strength in right and left limbs over time using 2 different methods: The Tufts Quantitative Neuromuscular Exam and Accurate Test of Limb Isometric Strength protocol. Then advanced linear regression statistical methods were applied to assess progression rates in each limb.ResultsThis report shows that linearized progression models can predict general slopes of decline with good accuracy. Critically, the data demonstrate that while overall decline is variable, there is a high degree of correlation between left and right muscle decline in ALS. This implies that irrespective of which muscle starts declining soonest or latest, their rates of decline following onset are more consistent.ConclusionsFirst, this study demonstrates a high degree of power when using unilateral treatment approaches to detect a slowing in disease progression in smaller groups of patients, thus allowing for paired statistical tests. These findings will be useful in transplantation trials that use muscle decline to track disease progression in ALS. Second, these findings discuss methods, such as tactical selection of muscle groups, which can improve the power efficiency of all ALS clinical trials
Practice Parameter: Therapies for Benign Paroxysmal Positional Vertigo (An Evidence-Based Review): Report of the Quality Standards Subcommittee of the American Academy of Neurologysymbol Symbol
American Academy of Neurology; BPPV = benign paroxysmal positional vertigo; CONSORT = Consolidated Standards of Reporting Trials; CRP = canalith repositioning procedure; NNT = number needed to treat
Artemin, a Novel Member of the GDNF Ligand Family, Supports Peripheral and Central Neurons and Signals through the GFRα3–RET Receptor Complex
AbstractThe glial cell line–derived neurotrophic factor (GDNF) ligands (GDNF, Neurturin [NTN], and Persephin [PSP]) signal through a multicomponent receptor system composed of a high-affinity binding component (GFRα1–GFRα4) and a common signaling component (RET). Here, we report the identification of Artemin, a novel member of the GDNF family, and demonstrate that it is the ligand for the former orphan receptor GFRα3–RET. Artemin is a survival factor for sensory and sympathetic neurons in culture, and its expression pattern suggests that it also influences these neurons in vivo. Artemin can also activate the GFRα1–RET complex and supports the survival of dopaminergic midbrain neurons in culture, indicating that like GDNF (GFRα1–RET) and NTN (GFRα2–RET), Artemin has a preferred receptor (GFRα3–RET) but that alternative receptor interactions also occur
Residual cognitive deficits 50 years after lead poisoning during childhood
The long term neurobehavioural consequences of childhood lead poisoning are not known. In this study adult subjects with a documented history of lead poisoning before age 4 and matched controls were examined with an abbreviated battery of neuropsychological tests including measures of attention, reasoning, memory, motor speed, and current mood. The subjects exposed to lead were inferior to controls on almost all of the cognitive tasks. This pattern of widespread deficits resembles that found in children evaluated at the time of acute exposure to lead rather than the more circumscribed pattern typically seen in adults exposed to lead. Despite having completed as many years of schooling as controls, the subjects exposed to lead were lower in lifetime occupational status. Within the exposed group, performance on the neuropsychological battery and occupational status were related, consistent with the presumed impact of limitations in neuropsychological functioning on everyday life. The results suggest that many subjects exposed to lead suffered acute encephalopathy in childhood which resolved into a chronic subclinical encephalopathy with associated cognitive dysfunction still evident in adulthood. These findings lend support to efforts to limit exposure to lead in childhood
Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy
OBJECTIVE
To expand the clinical phenotype of autosomal dominant congenital spinal muscular atrophy with lower extremity predominance (SMA-LED) due to mutations in the dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene.
METHODS
Patients with a phenotype suggestive of a motor, non-length-dependent neuronopathy predominantly affecting the lower limbs were identified at participating neuromuscular centers and referred for targeted sequencing of DYNC1H1.
RESULTS
We report a cohort of 30 cases of SMA-LED from 16 families, carrying mutations in the tail and motor domains of DYNC1H1, including 10 novel mutations. These patients are characterized by congenital or childhood-onset lower limb wasting and weakness frequently associated with cognitive impairment. The clinical severity is variable, ranging from generalized arthrogryposis and inability to ambulate to exclusive and mild lower limb weakness. In many individuals with cognitive impairment (9/30 had cognitive impairment) who underwent brain MRI, there was an underlying structural malformation resulting in polymicrogyric appearance. The lower limb muscle MRI shows a distinctive pattern suggestive of denervation characterized by sparing and relative hypertrophy of the adductor longus and semitendinosus muscles at the thigh level, and diffuse involvement with relative sparing of the anterior-medial muscles at the calf level. Proximal muscle histopathology did not always show classic neurogenic features.
CONCLUSION
Our report expands the clinical spectrum of DYNC1H1-related SMA-LED to include generalized arthrogryposis. In addition, we report that the neurogenic peripheral pathology and the CNS neuronal migration defects are often associated, reinforcing the importance of DYNC1H1 in both central and peripheral neuronal functions
Lying-down nystagmus and head-bending nystagmus in horizontal semicircular canal benign paroxysmal positional vertigo: are they useful for lateralization?
Heterogeneous ice nucleation on dust particles sourced from nine deserts worldwide – Part 2: Deposition nucleation and condensation freezing
Mineral dust particles from deserts are amongst the most common
ice nucleating particles in the atmosphere. The mineralogy of desert dust
differs depending on the source region and can further fractionate during the
dust emission processes. Mineralogy to a large extent explains the ice
nucleation behavior of desert aerosol, but not entirely. Apart from pure
mineral dust, desert aerosol particles often exhibit a coating or are mixed with small amounts of
biological material. Aging on the ground or
during atmospheric transport can deactivate nucleation sites, thus strong
ice nucleating minerals may not exhibit their full potential. In the partner
paper of this work, it was shown that mineralogy determines most but not
all of the ice nucleation behavior in the immersion mode found for desert dust.
In this study, the influence of semi-volatile organic compounds and the
presence of crystal water on the ice nucleation behavior of desert aerosol is
investigated. This work focuses on the deposition and condensation ice
nucleation modes at temperatures between 238 and 242 K of 18 dust samples
sourced from nine deserts worldwide. Chemical imaging of the particles' surface
is used to determine the cause of the observed differences in ice nucleation.
It is found that, while the ice nucleation ability of the majority of the dust
samples is dominated by their quartz and feldspar content, in one
carbonaceous sample it is mostly caused by organic matter, potentially
cellulose and/or proteins. In contrast, the ice nucleation ability of
an airborne Saharan sample is found to be diminished, likely by semi-volatile
species covering ice nucleation active sites of the minerals. This study
shows that in addition to mineralogy, other factors such as organics and
crystal water content can alter the ice nucleation behavior of desert aerosol
during atmospheric transport in various ways.</p
Birch leaves and branches as a source of ice-nucleating macromolecules
Birch pollen are known to release ice-nucleating macromolecules (INM), but
little is known about the production and release of INM from other parts of
the tree. We examined the ice nucleation activity of samples from 10
different birch trees (Betula spp.). Samples were taken from nine
birch trees in Tyrol, Austria, and from one tree in a small urban park in
Vienna, Austria. Filtered aqueous extracts of 30 samples of leaves, primary
wood (new branch wood, green in colour, photosynthetically active), and
secondary wood (older branch wood, brown in colour, with no photosynthetic
activity) were analysed in terms of ice nucleation activity using VODCA
(Vienna Optical Droplet Crystallization Analyser), a cryo
microscope for emulsion samples. All samples contained ice-nucleating
particles in the submicron size range. Concentrations of ice nuclei ranged
from 6.7×104 to 6.1×109 mg−1 sample. Mean
freezing temperatures varied between −15.6 and −31.3 °C; the
range of temperatures where washes of birch pollen and dilutions thereof
typically freeze. The freezing behaviour of three concentrations of birch
pollen washing water (initial wash, 1 : 100, and 1 : 10 000) were
significantly associated with more than a quarter of our samples, including
some of the samples with highest and lowest activity. This indicates a
relationship between the INM of wood, leaves, and pollen. Extracts derived
from secondary wood showed the highest concentrations of INM and the highest
freezing temperatures. Extracts from the leaves exhibited the highest
variation in INM and freezing temperatures. Infrared spectra of the extracts
and tested birch samples show qualitative similarity, suggesting the chemical
components may be broadly similar.</p
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