Glycation in Parkinson's disease and Alzheimer's disease

Glycation is a spontaneous age‐dependent posttranslational modification that can impact the structure and function of several proteins. Interestingly, glycation can be detected at the periphery of Lewy bodies in the brain in Parkinson's disease. Moreover, α‐synuclein can be glycated, at least under experimental conditions. In Alzheimer's disease, glycation of amyloid β peptide exacerbates its toxicity and contributes to neurodegeneration. Recent studies establish diabetes mellitus as a risk factor for several neurodegenerative disorders, including Parkinson's and Alzheimer's diseases. However, the mechanisms underlying this connection remain unclear. We hypothesize that hyperglycemia might play an important role in the development of these disorders, possibly by also inducing protein glycation and thereby dysfunction, aggregation, and deposition. Here, we explore protein glycation as a common player in Parkinson's and Alzheimer's diseases and propose it may constitute a novel target for the development of strategies for neuroprotective therapeutic interventions. © 2016 International Parkinson and Movement Disorder Society     

Rating scales for behavioral symptoms in Huntington's disease: Critique and recommendations

Behavioral symptoms are an important feature of Huntington's disease and contribute to impairment in quality of life. The Movement Disorder Society commissioned the assessment of the clinimetric properties of rating scales in Huntington's disease to make recommendations regarding their use, following previously used standardized criteria. A systematic literature search was conducted to identify the scales used to assess behavioral symptoms in Huntington's disease. For the purpose of this review, 7 behavioral domains were deemed significant in Huntington's disease: irritability, anxiety, depression, apathy, obsessive‐compulsive behaviors, psychosis, and suicidal ideation. We included a total of 27 behavioral rating scales, 19 of which were of a single behavioral domain and the remaining 8 scales included multiple behavioral domains. Three rating scales were classified as “recommended” exclusively for screening purposes: the Irritability Scale for irritability, the Beck Depression Inventory‐II, and the Hospital Anxiety and Depression Scale for depression. There were no “recommended” scales for other purposes such as diagnosis, severity, or change in time or to treatment. The main challenges identified for assessment of behavioral symptoms in Huntington's disease are the co‐occurrence of multiple behavioral symptoms, the particular features of a behavioral symptom in Huntington's disease, and the need to address stage‐ and disease‐specific features, including cognitive impairment and lack of insight. The committee concluded that there is a need to further validate currently available behavioral rating scales in Huntington's disease to address gaps in scale validation for specific behavioral domains and purpose of use. © 2016 International Parkinson and Movement Disorder Society     

Tracking online poker problem gamblers with player account‐based gambling data only

The aim was to develop and validate an instrument to track online problem poker gamblers with player account‐based gambling data (PABGD). We emailed an invitation to all active poker gamblers on the online gambling service provider Winamax. The 14,261 participants completed the Problem Gambling Severity Index (PGSI). PGSI served as a gold standard to track problem gamblers (i.e., PGSI ≥ 5). We used a stepwise logistic regression to build a predictive model of problem gambling with PABGD, and validated it. Of the sample 18% was composed of online poker problem gamblers. The risk factors of problem gambling included in the predictive model were being male, compulsive, younger than 28 years, making a total deposit > 0 euros, having a mean loss per gambling session > 1.7 euros, losing a total of > 45 euros in the last 30 days, having a total stake > 298 euros, having > 60 gambling sessions in the last 30 days, and multi‐tabling. The tracking instrument had a sensitivity of 80%, and a specificity of 50%. The quality of the instrument was good. This study illustrates the feasibility of a method to develop and validate instruments to track online problem gamblers with PABGD only. Copyright © 2016 John Wiley & Sons, Ltd.     

Intramuscular nerve distribution pattern of ankle invertor muscles in human cadaver using sihler stain

Introduction: We sought to the ideal sites for botulinum toxin injection by examining the intramuscular nerve patterns of the ankle invertors. Methods: A modified Sihler method was performed on the flexor hallucis longus, tibialis posterior, and flexor digitorum longus muscles (10 specimens each). The muscle origins, nerve entry points, and intramuscular arborization areas were measured as a percentage of the total distance from the most prominent point of the lateral malleolus (0%) to the fibular head (100%). Results: Intramuscular arborization patterns were observed at 20–50% for the flexor hallucis longus, 70–80% for the tibialis posterior, and 30–40% for the flexor digitorum longus. Conclusions: These findings suggest that treatment of muscle spasticity of the ankle invertors involves botulinum toxin injections in specific areas. These areas, corresponding to the areas of maximum arborization, are recommended as the most effective and safest points for injection. Muscle Nerve 53 : 742–747, 2016     

Nerve ultrasound protocol in differentiating chronic immune‐mediated neuropathies

Introduction: In this study we evaluated a new neuropathy ultrasound protocol (NUP) for differentiating chronic immune‐mediated neuropathies. Methods: The NUP was evaluated in 110 patients with clinical presentations of chronic immune‐mediated neuropathy. All patients were first evaluated clinically and electrophysiologically and divided into 4 polyneuropathy groups: (a) symmetric demyelinating; (b) symmetric axonal; (c) asymmetric demyelinating; and (d) asymmetric axonal. During step 2, the NUP was evaluated prospectively for all 4 study groups. Results: Overall, the NUP led to correct classification in 42 of 49 (85.7%) patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 13 of 15 (86.9%) with multifocal motor neuropathy (MMN), and 5 of 5 (100%) with multifocal‐acquired demyelinating sensory and motor neuropathy (MADSAM). The NUP had >80% sensitivity and specificity in distinguishing CIDP, MMN, and MADSAM in all 4 study groups. Conclusions: The NUP is a useful addition in the differential diagnosis of chronic immune‐mediated neuropathies in everyday practice. Muscle Nerve 54 : 864–871, 2016     

Estimating the effect of endogenous dopamine on baseline [11C]‐(+)‐PHNO binding in the human brain

Endogenous dopamine (DA) levels at dopamine D_2/3 receptors (D_2/3R) have been quantified in the living human brain using the agonist radiotracer [¹¹C]‐(+)‐PHNO. As an agonist radiotracer, [¹¹C]‐(+)‐PHNO is more sensitive to endogenous DA levels than antagonist radiotracers. We sought to determine the proportion of the variance in baseline [¹¹C]‐(+)‐PHNO binding to D_2/3Rs which can be accounted for by variation in endogenous DA levels. This was done by computing the Pearson's coefficient for the correlation between baseline binding potential (BP_ND) and the change in BP_ND after acute DA depletion, using previously published data. All correlations were inverse, and the proportion of the variance in baseline [¹¹C]‐(+)‐PHNO BP_ND that can be accounted for by variation in endogenous DA levels across the striatal subregions ranged from 42‐59%. These results indicate that lower baseline values of [¹¹C]‐(+)‐PHNO BP_ND reflect greater stimulation by endogenous DA. To further validate this interpretation, we sought to examine whether these data could be used to estimate the dissociation constant (Kd) of DA at D_2/3R. In line with previous in vitro work, we estimated the in vivo Kd of DA to be around 20 nM. In summary, the agonist radiotracer [¹¹C]‐(+)‐PHNO can detect the impact of endogenous DA levels at D_2/3R in the living human brain from a single baseline scan, and may be more sensitive to this impact than other commonly employed radiotracers.