Ulnar neuropathy with abnormal non-localizing electrophysiology: Clinical,electrophysiological and ultrasound findings

Objective

To systematically study demographic, clinical, electrophysiological and nerve ultrasound characteristics of ulnar neuropathy with abnormal non-localizing electrophysiology (NL-UN) and further define the utility of ultrasound over and above the conventional electro-diagnostic approach.

Electrophysiology in Fisher syndrome

Fisher syndrome (FS), a variant of Guillain–Barré syndrome (GBS), is characterized by the clinical triad of ophthalmoplegia, ataxia, and areflexia. The lesion sites for these unique clinical features include the oculomotor nerves and group 1a neurons in the dorsal root ganglion, and the presence of FS is determined by the expression of ganglioside GQ1b in the human nervous system. Neurophysiological findings suggest that ataxia and areflexia are due to an impaired proprioceptive afferent system. Typically, the soleus H-reflex is absent and a body-sway analysis using posturography shows a 1-Hz peak, which indicates proprioception dysfunction. Sensory nerve action potentials and somatosensory-evoked potentials are abnormal in approximately 30% of FS patients, indicating the occasional involvement of cutaneous (group 2) afferents. During the disease course, approximately 15% of FS patients suffer an overlap of axonal GBS with nerve conduction abnormalities that reflect axonal dysfunction. This review summarizes electrophysiological abnormalities and their clinical significance in FS.     

Electrophysiologic features of ulnar neuropathy in childhood and adolescence

Objective

To analyze patterns of nerve injury in pediatric ulnar neuropathy (PUN).

Non-neutral nonsynonymous single nucleotide polymorphisms in human ABC transporters: the first comparison of six prediction methods

Nonsynonymous single nucleotide polymorphisms (nsSNPs) in coding regions that can lead to amino acid changes may cause alteration of protein function and account for susceptibility to disease and altered drug/xenobiotic response. Abundant nsSNPs have been found in genes coding for human ATP-binding cassette (ABC) transporters, but there is little known about the relationship between the genotype and phenotype of nsSNPs in these membrane proteins. In addition, it is unknown which prediction method is better suited for the prediction of non-neutral nsSNPs of ABC transporters. We have identified 2,172 validated nsSNPs in 49 human ABC transporter genes from the Ensembl genome database and the NCBI SNP database. Using six different algorithms, 41 to 52% of nsSNPs in ABC transporter genes were predicted to have functional impacts on protein function. Predictions largely agreed with the available experimental annotations. Overall, 78.5% of non-neutral nsSNPs were predicted correctly as damaging by SNAP, which together with SIFT and PolyPhen, was superior to the prediction methods Pmut, PhD-SNP, and Panther. This study also identified any amino acids that were likely to be functionally critical but have not yet been studied experimentally. There was significant concordance between the predicted results of SIFT and PolyPhen. Evolutionarily non-neutral (destabilizing) amino acid substitutions are predicted to be the basis for the pathogenic alteration of ABC transporter activity that is associated with disease susceptibility and altered drug/xenobiotic response.     

Opposite effects of nitric oxide on rod and cone photoreceptors of rat retina in situ

In the light-adapted vertebrate retina, nitric oxide (NO) modulates synaptic transmission between photoreceptors and second-order neurons. Although NO is believed to be a mediator of adaptation, its effect on photoreceptors in situ is not known yet. Therefore, we studied rod and cone activities in rat eyes in situ, using the electroretinogram (ERG). Rod and cone ERGs were functionally isolated by intravitreal 20 mM glutamate, which suppressed the activity of all retinal cells except rods and cones for about 90 min. The addition of NO-donor, SNAP, to the glutamate solution decreased the amplitude of the rod single-flash ERG by ∼40%, compared to the amplitude of the rod ERG isolated by glutamate alone, but it increased the amplitude of the isolated, intense paired-flash cone ERG by ∼40%. An excess of the NO-scavenger, CPTIO, had no significant effect on either rod or cone ERGs. A broad-spectrum NO-synthase inhibitor, L-NAME, increased the amplitude of the rod ERG by ∼50%, but had no significant effect on the cone ERG. We suggest that NO directly modulates the light-evoked activity of rod and cone photoreceptors in situ, but in opposite ways.     

Immunohistochemical Localization of SNARE Proteins in Dental Pulp and Periodontal Ligament of the Rat Incisor

Distribution of three soluble N‐ethylmaleimide‐sensitive fusion protein attachment protein receptor (SNARE) proteins, syntaxin‐1, synaptosomal‐associated protein of 25 kDa (SNAP‐25), and vesicle‐associated membrane protein‐2 (VAMP‐2), was examined in dental pulp and periodontal ligament of the rat incisor. In the trigeminal ganglion, syntaxin‐1 and SNAP‐25 immunoreactivity was predominately detected in medium‐ to large‐sized neurons. Most syntaxin‐1 immunoreactive neurons expressed SNAP‐25. In contrast, VAMP‐2 was localized in small‐ to medium‐sized neurons and in slender‐shaped cells surrounding SNAP‐25‐immunopositive neurons. When the inferior alveolar nerve, one of the mandibular nerve branches innervating the dental pulp and periodontal ligament, was ligated, SNARE proteins accumulated at the site proximal to the ligation. In the incisor dental pulp, all nerve fibers displayed immunoreactivity for syntaxin‐1, SNAP‐25, and VAMP‐2. In the periodontal ligament of the incisor, almost all nerve fibers displayed both syntaxin‐1 and SNAP‐25 immunoreactivity, but lacked VAMP‐2 immunoreactivity. SNAP‐25 protein expression was localized around the vesicle membranes at the axon terminal of the periodontal mechanoreceptors. These present data suggest that these three SNARE proteins are synthesized at the trigeminal ganglion, transported centrally and peripherally, and expressed in sensory endings where apparent synapses are not present. Because those proteins participate in docking and exocytosis of synapse vesicles in the central nervous system, they might also contribute to vesicle exocytosis at receptive fields where apparent synapses are not present. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.     

Astrocyte lipid metabolism is critical for synapse development and function in vivo

The brain is considered to be autonomous in lipid synthesis with astrocytes producing lipids far more efficiently than neurons. Accordingly, it is generally assumed that astrocyte‐derived lipids are taken up by neurons to support synapse formation and function. Initial confirmation of this assumption has been obtained in cell cultures, but whether astrocyte‐derived lipids support synapses in vivo is not known. Here, we address this issue and determined the role of astrocyte lipid metabolism in hippocampal synapse formation and function in vivo. Hippocampal protein expression for the sterol regulatory element‐binding protein (SREBP) and its target gene fatty acid synthase (Fasn) was found in astrocytes but not in neurons. Diminishing SREBP activity in astrocytes using mice in which the SREBP cleavage‐activating protein (SCAP) was deleted from GFAP‐expressing cells resulted in decreased cholesterol and phospholipid secretion by astrocytes. Interestingly, SCAP mutant mice showed more immature synapses, lower presynaptic protein SNAP‐25 levels as well as reduced numbers of synaptic vesicles, indicating impaired development of the presynaptic terminal. Accordingly, hippocampal short‐term and long‐term synaptic plasticity were defective in mutant mice. These findings establish a critical role for astrocyte lipid metabolism in presynaptic terminal development and function in vivo. GLIA 2017;65:670–682     

Simultaneous noncontrast angiography and intraPlaque hemorrhage (SNAP) imaging for carotid atherosclerotic disease evaluation

A simultaneous noncontrast angiography and intraplaque hemorrhage (SNAP) MR imaging technique is proposed to detect both luminal stenosis and hemorrhage in atherosclerosis patients in a single scan. Thirteen patients with diagnosed carotid atherosclerotic plaque were admitted after informed consent. All scans were performed on a 3T MR imaging system with SNAP, 2D time‐of‐flight and magnetization‐prepared 3D rapid acquisition gradient echo sequences. The SNAP sequence utilized a phase sensitive acquisition, and was designed to provide positive signals corresponding to intraplaque hemorrhage and negative signals corresponding to lumen. SNAP images were compared to time‐of‐flight images to evaluate lumen size measurements using linear mixed models and the intraclass correlation coefficient. Intraplaque hemorrhage identification accuracy was evaluated by comparing to magnetization‐prepared 3D rapid acquisition gradient echo images using Cohen's Kappa. Diagnostic quality SNAP images were generated from all subjects. Quantitatively, the lumen size measurements by SNAP were strongly correlated (intraclass correlation coefficient = 0.96, P < 0.001) with those measured by time‐of‐flight. For intraplaque hemorrhage detection, strong agreement (κ = 0.82, P < 0.001) was also identified between SNAP and magnetization‐prepared 3D rapid acquisition gradient echo images. In conclusion, a SNAP imaging technique was proposed and shows great promise for imaging both lumen size and carotid intraplaque hemorrhage with a single scan. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

The persistence and stability of psychiatric problems in adolescents with autism spectrum disorders

Background: Psychiatric problems are common in autism spectrum disorders (ASDs), but the reasons are poorly understood. We use a longitudinal population‐representative cohort to examine for the first time the persistence of psychiatric problems and to identify risk factors for their occurrence and stability. Methods: Eighty‐one 16‐year olds (75 male, six female), initially seen at 12 years, were re‐assessed using the parent‐report Strengths and Difficulties Questionnaire (SDQ). Child, family and contextual characteristics from age 12 were tested as risk factors for psychopathology. Results: Prevalence rates varied depending on whether general population or ASD‐specific SDQ cut‐offs were used. While the former suggested a decrease in psychiatric problems over time, the ASD‐specific cut‐offs showed no significant differences. With the exception of ADHD, the ASD‐specific cut‐offs identified a smaller proportion of individuals as ‘affected’ than did the general population cut‐offs. There was longitudinal domain specificity, with parent correlations ranging from 0.50 to 0.58 and teacher SDQ reports at age 12 correlating 0.33–0.53 with parent reports at 16 years. In examining the role of risk factors, lower IQ and adaptive functioning predicted higher hyperactivity and total difficulties scores. Greater emotional problems at 16 were predicted by poorer maternal mental health, family‐based deprivation and lower social class. Improvement from 12 to 16 years in conduct problems was predicted by greater neighbourhood deprivation and special school attendance. Conclusions: This is the first longitudinal study of other psychiatric symptoms in ASD. Additional psychiatric problems in ASD are persistent and domain‐specific from childhood to adolescence. The finding that age‐related reduction in SDQ symptoms does not apply when ASD‐specific cut‐offs are used requires further evaluation using diagnostic measures. Only a few of the expected risk factor‐psychopathology predictions expected from general population studies were found, raising the possibility that the causes of psychopathology in ASD differ from those in the general population.     

Rewarding Healthy Food Choices in SNAP: Behavioral Economic Applications

Context

American obesity rates continue to escalate, but an effective policy response remains elusive. Specific changes to the Supplemental Nutrition Assistance Program (SNAP) have been proposed as one way to improve nutrition and combat obesity among lower-income populations. While current SNAP proposals hold promise, some important challenges still remain.

Methods

We discuss the four most common recommendations for changes to SNAP and their benefits and limitations. We then propose three new delivery options for SNAP that take advantage of behavioral economic insights and encourage the selection of healthy foods.

Findings

Although the existing proposals could help SNAP recipients, they often do not address some important behavioral impediments to buying healthy foods. We believe that behavioral economics can be used to design alternative policies with several advantages, although we recognize and discuss some of their limitations. The first proposal rewards healthy purchases with more SNAP funds and provides an additional incentive to maintain healthier shopping patterns. The second proposal uses the opportunity to win prizes to reward healthy food choices, and the prizes further support healthier habits. The final proposal simplifies healthy food purchases by allowing individuals to commit their SNAP benefits to more nutritious selections in advance.

Conclusions

Reforming the delivery structure of SNAP''s benefits could help improve nutrition, weight, and overall health of lower-income individuals. We advocate for more and diverse SNAP proposals, which should be tested and, possibly, combined. Their implementation, however, would require political will, administrative capacity, and funding.