Functional or not functional; that's the question: Can we predict the diagnosis functional movement disorder based on associated features?

BACKGROUND AND PURPOSE: Functional movement disorders (FMDs) pose a diagnostic challenge for clinicians. Over the years several associated features have been shown to be suggestive for FMDs. Which features mentioned in the literature are discriminative between FMDs and non-FMDs were examined in a large cohort. In addition, a preliminary prediction model distinguishing these disorders was developed based on differentiating features. METHOD: Medical records of all consecutive patients who visited our hyperkinetic outpatient clinic from 2012 to 2019 were retrospectively reviewed and 12 associated features in FMDs versus non-FMDs were compared. An independent t test for age of onset and Pearson chi-squared analyses for all categorical variables were performed. Multivariate logistic regression analysis was performed to develop a preliminary predictive model for FMDs. RESULTS: A total of 874 patients were eligible for inclusion, of whom 320 had an FMD and 554 a non-FMD. Differentiating features between these groups were age of onset, sex, psychiatric history, family history, more than one motor phenotype, pain, fatigue, abrupt onset, waxing and waning over long term, and fluctuations during the day. Based on these a preliminary predictive model was computed with a discriminative value of 91%. DISCUSSION: Ten associated features are shown to be not only suggestive but also discriminative between hyperkinetic FMDs and non-FMDs. Clinicians can use these features to identify patients suspected for FMDs and can subsequently alert them to test for positive symptoms at examination. Although a first preliminary model has good predictive accuracy, further validation should be performed prospectively in a multi-center study.

The diagnostic value of clinical neurophysiology in hyperkinetic movement disorders: A systematic review.

INTRODUCTION: To guide the neurologist and neurophysiologist with interpretation and implementation of clinical neurophysiological examinations, we aim to provide a systematic review on evidence of electrophysiological features used to differentiate between hyperkinetic movement disorders. METHODS: A PRISMA systematic search and QUADAS quality evaluation has been performed in PubMed to identify diagnostic test accuracy studies comparing electromyography and accelerometer features. We included papers focusing on tremor, dystonia, myoclonus, chorea, tics and ataxia and their functional variant. The features were grouped as 1) basic features (e.g., amplitude, frequency), 2) the influence of tasks on basic features (e.g., entrainment, distraction), 3) advanced analyses of multiple signals, 4) and diagnostic tools combining features. RESULTS: Thirty-eight cross-sectional articles were included discussing tremor (n = 28), myoclonus (n = 5), dystonia (n = 5) and tics (n = 1). Fifteen were rated as 'high quality'. In tremor, the basic and task-related features showed great overlap between clinical tremor syndromes, apart from rubral and enhanced physiological tremor. Advanced signal analyses were best suited for essential, parkinsonian and functional tremor, and cortical, non-cortical and functional jerks. Combinations of electrodiagnostic features could identify essential, enhanced physiological and functional tremor. CONCLUSION: Studies into the diagnostic accuracy of electrophysiological examinations to differentiate between hyperkinetic movement disorders have predominantly been focused on clinical tremor syndromes. No single feature can differentiate between them all; however, a combination of analyses might improve diagnostic accuracy.

Effect of atropine and somatostatin on bombesin-stimulated plasma gastrin, cholecystokinin and pancreatic polypeptide in man.

Infusion of the neuropeptide bombesin stimulates the secretion of several gastrointestinal hormones by an unknown mechanism. We have investigated the effects of atropine (15 ng/kg as bolus followed by 2.5 ng/kg X 30 min) and somatostatin (125 micrograms as i.v. bolus followed by 62.5 micrograms/30 min) on the stimulation of 3 hormones (gastrin, cholecystokinin and pancreatic polypeptide) by 60 pmol/kg X 20 min bombesin in 6 healthy volunteers. Plasma samples for measurement of hormones by sensitive and specific radioimmunoassays were obtained at -5, 0, 2.5, 5, 7.5, 10, 15, 20, 25 and 30 min. Bombesin induced significant increases in plasma gastrin (12 +/- 2 to 34 +/- 3 pM; P less than 0.0005), cholecystokinin (1.2 +/- 0.2 to 8.9 +/- 0.7 pM; P less than 0.0001) and pancreatic polypeptide (22 +/- 4 to 72 +/- 19 pM; P less than 0.05). There were great differences between the effects of atropine and somatostatin on the hormonal responses to bombesin. Atropine slightly increased the response of gastrin by 19% and that of cholecystokinin by 15%, but strongly inhibited the bombesin-stimulated pancreatic polypeptide secretion by 97%. On the other hand, somatostatin inhibited the bombesin-induced secretion of gastrin by 48%, cholecystokinin by 82% and pancreatic polypeptide by 107%. These results point to considerable qualitative and quantitative differences in the stimulatory mechanisms of bombesin on the hormones studied.

Effect of bombesin and cholecystokinin on plasma immunoreactive trypsin in humans.

Since bombesin is a potent stimulus of the release of cholecystokinin (CCK), it has been suggested that the stimulatory effect of bombesin on pancreatic enzyme secretion is mediated by CCK. The present study was undertaken to determine the role of CCK in the bombesin-induced stimulation of plasma immunoreactive trypsin. Plasma CCK was measured by radioimmunoassay using the antibody T204, which binds to all biologically active sulfated COOH-terminal CCK-peptides. Plasma trypsin was also measured by radioimmunoassay. Infusion of 5 ng/kg/min bombesin in 6 healthy volunteers increased plasma CCK from 1.2 +/- 0.2-8.9 +/- 0.7 pM (p less than 0.0001). The peak increment in plasma CCK during bombesin (9.3 +/- 0.6 pM) was accompanied by a significant rise in plasma trypsin from 206 +/- 21-334 +/- 44 ng/ml (p less than 0.01). However, when similar increases in plasma CCK were achieved by infusion of 0.018 CU/kg/min CCK-33 (9.9 +/- 0.8 pM) or by intraduodenal instillation of 250 ml 20% Intralipid (9.7 +/- 1.9 pM), no significant changes in plasma trypsin were observed. It is therefore concluded that the stimulatory effect of bombesin on plasma immunoreactive trypsin is not mediated by CCK.

Influence of Initial C/N Ratio on Chemical and Microbial Composition during Long Term Composting of Straw.

Shredded straw of Miscanthus was composted in 800-L boxes with different amounts of pig slurry added as nitrogen source. The impact of the different initial C/N ratios (11, 35, 47, 50, and 54) on the composting process and the end product was evaluated by examining chemical and microbiological parameters during 12 months of composting. Low initial C/N ratios caused a fast degradation of fibers during the first three months of composting (hemicellulose: 50-80%, cellulose: 40-60%), while high initial C/N ratios resulted in 10-20% degradation of both hemicellulose and cellulose. These differences were reflected in the microbial biomass and respiration, which initially were higher in low C/N treatments than in high C/N treatments. After 12 months of composting, this situation was reversed. Composts with high initial C/N ratios had high microbial biomass (15-20 mg ATP g-1 OM) and respiration rates (200 mg CO2 h-1 g-1 OM) compared to treatments with low initial C/N ratios (less than 10 mg ATP g-1 OM and 25 mg CO2 h-1 g-1 OM). This could be explained by the microorganisms being nitrogen limited in the high C/N ratio treatments. In the low C/N ratio treatments, without nitrogen limitation, the high activity in the beginning decreased with time because of exhaustion of easily available carbon. Different nitrogen availability was also seen in the nitrification patterns, since nitrate was only measured in significant amounts in the treatments with initial C/N ratios of 11 and 35. The microbial community structure (measured as phospholipid fatty acid, PLFA, profile) was also affected by the initial C/N ratios, with lower fungal/bacterial ratios in the low compared to the high C/N treatments after 12 months of composting. However, in the low C/N treatments higher levels of PLFAs indicative of thermophilic gram-positive bacteria were found compared to the high C/N treatments. This was caused by the initial heating phase being longer in the low than in the high C/N treatments. The different fungal/bacterial ratios could also be explained by the initial heating phase, since a significant correlation between this ratio and heat generated during the initial composting phase was found.

Effect of atropine and somatostatin on bombesin-stimulated plasma immunoreactive trypsin release in man.

This study was undertaken to determine the effect of atropine and somatostatin, two inhibitors of intraduodenal pancreatic enzyme secretion, on bombesin-stimulated release of plasma immunoreactive trypsin in 6 healthy volunteers. Infusion of 5 ng/kg.min bombesin during 30 min induced significant increases in plasma trypsin from 206 +/- 20 to 334 +/- 44 ng/ml (p less than 0.01). Atropine (15 ng/kg as i.v. bolus followed by 5 ng/kg.h) had no influence on the bombesin-stimulated increase in plasma immunoreactive trypsin (207 +/- 20 to 326 +/- 54 ng/ml). Somatostatin (125 micrograms as i.v. bolus followed by 125 micrograms/h) also failed to inhibit the plasma trypsin response to bombesin (207 +/- 18 to 663 +/- 166 ng/ml). These results point to major differences in the regulation of plasma and intraduodenal trypsin secretion.