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Mild cognitive impairment, especially executive dysfunction might occur early in the course of Parkinson's disease. Cognitive training is thought to improve cognitive performance. However, transfer of improvements achieved in paper and pencil tests into daily life has been difficult. The aim of the current study was to investigate whether a multimodal cognitive rehabilitation programme including physical exercises might be more successful than cognitive training programmes without motor training. 240 PD-patients were included in the study and randomly allocated to three treatment arms, group A cognitive training, group B cognitive training and transfer training and group C cognitive training, transfer training and psychomotor and endurance training. The primary outcome measure was the ADAS-Cog. The secondary outcome measure was the SCOPA-Cog. Training was conducted for 4 weeks on a rehabilitation unit, followed by 6 months training at home. Caregivers received an education programme. The combination of cognitive training using paper and pencil and the computer, transfer training and physical training seems to have the greatest effect on cognitive function. Thus, patients of group C showed the greatest improvement on the ADAS-Cog and SCOPA-COG and were more likely to continue with the training programme after the study. [ABSTRACT FROM AUTHOR]

Symptoms of Parkinson's disease (PD) progress despite optimized medical treatment. The present study investigated the effects of a flexibility and relaxation programme, walking, and Nordic walking (NW) on walking speed, stride length, stride length variability, Parkinson-specific disability (UPDRS), and health-related quality of life (PDQ 39). 90 PD patients were randomly allocated to the 3 treatment groups. Patients participated in a 6-month study with 3 exercise sessions per week, each lasting 70 min. Assessment after completion of the training showed that pain was reduced in all groups, and balance and health-related quality of life were improved. Furthermore, walking, and Nordic walking improved stride length, gait variability, maximal walking speed, exercise capacity at submaximal level, and PD disease-specific disability on the UPDRS in addition. Nordic walking was superior to the flexibility and relaxation programme and walking in improving postural stability, stride length, gait pattern and gait variability. No significant injuries occurred during the training. All patients of the Nordic walking group continued Nordic walking after completing the study. [ABSTRACT FROM AUTHOR]

Exercise training is often recommended for patients who have Parkinson's disease. Until the debate about the pathophysiologic cause of impaired movement in parkinsonism is settled, it is difficult to develop a specific exercise treatment for symptoms that include hypokinesia, tremor, and muscular rigidity. Most of the published studies show a benefit of exercise training, and we provide an overview of the most essential studies and present conclusions for a practical approach to exercise training in parkinsonism. [ABSTRACT FROM AUTHOR]

AIM: :To evaluate the suitability of panoramic radiographs obtained with two different machines for clinical use. Material and methods: Three observers assessed 111 pairs of panoramic radiographs taken with the Scanora® (Soredex, Orion Corp., Helsinki, Finland) programme 001, and the Orthophos Plus® (Sirona, Bensheim, Germany), programme P1 respectively, for visualisation of seven anatomical structures on each side, on a 5-point scale where 1=very good. The median values were computed and a descriptive analysis performed. Interrater and intrarater agreement were expressed as weighted kappa. Results: The median values of both Scanora® and Orthophos® radiographs were the same, scoring 2. The intra- and inter-observer agreement was generally poor and similar for both machines. Conclusions: The two panoramic machines were both given good ratings for evaluation of anatomical structures. The differences were very small and suggest that both machines are suitable for clinical use. [ABSTRACT FROM AUTHOR]

OBJECTIVE: :To evaluate a novel fixation system for reproducible radiography in edentulous patients. Methods: A conventional extra-oral fixation system was modified with a filmholder and adjustable scales. For measuring reproducibility and angulation errors two rods and two balls were fixed on the alveolar crests of the maxilla and the mandible and angular variations were measured. One hundred radiographs of a conventional phantom were taken by one of the authors and by ten dental students. The angular disparity was calculated and intra- and interoperator precision determined. Results: The average time taken to assemble the fixation system was 4 min. The 95% confidence interval for precision of the single operator was less than 2.5° in both the maxilar and mandible. The 95% confidence interval for precision of the ten students was less than 2.2° for the maxilla and 2.7° for the mandible. There was no significant difference (P>0.05) in interoperator precision. Conclusion: The novel extra-oral fixation system appears to be a potential means of obtaining reproducible radiographs of edentulous patients. [ABSTRACT FROM AUTHOR]

Objective: To explain the formation of triple images on panoramic radiographs. Methods: A metal test object was placed in defined positions in relation to movement path of a panoramic X-ray beam. Results: The test object was portrayed once, twice or three times with varying degrees of distortion depending on its location. Triple images were formed when the test object was located in a specific diamond-shaped area distal to the path of the rotation centre of the X-ray beam. Conclusions: The formation of triple images on panoramic radiographs can be explained on the basis of known projection geometry. [ABSTRACT FROM AUTHOR]

This report describes a case of Stafne's cavity in combination with an extra-osseous course of the mandibular neurovascular bundle in the upper region of the bony defect. The radiographic approach and diagnosis including CT examination are presented. [ABSTRACT FROM AUTHOR]

Abstract Background In idiopathic Parkinson's disease (IPD) transcranial sonography (TCS) represents an alternative diagnostic method to verify clinical diagnosis. Although the phenomenon of an increased echogenicity of the Substantia nigra (SN) is well known this method is still not widly used in the diagnostic workup. Until now reliability of this method is still a matter of debate, partly because data only existed from a few laboratories using the same ultrasound machine. Therefore our study was conducted to test the reliability of this method by using a different ultrasound device and examining a large population of control and IPD subjects by two examiners to calculate interobserver reliability. Method In this study echogenicity of SN was examined in 199 IPD patients and 201 control subjects. All individuals underwent a neurological assessment including Perdue pegboard test and Webster gait test. Using a Sonos 5500 ultrasound device area of SN was measured, echogenicity of raphe, red nuclei, thalamus, caudate and lenticular nuclei, width of third and lateral ventricle were documented. Results We found a highly characteristic enlargement of the SN echogenic signal in IPD. The cut-off value for the SN area was established using a ROC curve with a sensitivity of 95% corresponding to an area of SN of 0.2 cm2 and was found to be equivalent to the cut-off values of other studies using different ultrasound devices. Conclusions Our study shows that TCS is a reliable and highly sensitive tool for differentiation of IPD patients from individuals without CNS disorders.

Background/aim: The lymph node status has high prognostic relevance in head and neck squamous cell carcinoma (HNSCC). This study aimed to address the hypothesis that the number of positive nodes and the nodal ratio have a prognostic impact on survival in HNSCC., Patients and Methods: A retrospective analysis of 221 patients with HNSCC and clinical N+ status who underwent a neck dissection during primary surgery or after definitive radio(chemo)therapy was performed. The possible influence of age, sex, TNM stage, number of positive nodes and nodal ratio on survival was analyzed by univariate and multivariate Cox models and log-rank tests., Results: On average, 30.1 lymph nodes were removed and 4.96 metastases were detected. The mean nodal ratio was 9.4%, the median nodal ratio was 5.3%. Multivariate analysis demonstrated a nodal ratio of ≥6-<12.5% [hazard ratio (HR)=2.33, 95% confidence interval (CI)=1.24-4.37; p=0.008] and of ≥12.5% (HR=2.86, 95% CI=1.40-5.84; p=0.004) compared to nodal ratio 0, number of positive nodes pN=1 compared to number of positive nodes=0 (HR=2.02, 95% CI=1.08-3.80. p=0.029), as well as N3 compared to N0 (HR=8.10, 95% CI=1.89-34.66; p=0.005), and Mx compared to M0 (HR of 2.76, 95% CI=1.59-4,79, p≤0.001) were of main importance for poor prognosis. Postoperative radio(chemo)therapy after surgery was associated with prolonged survival in multivariate analysis (HR=0.37, 95% CI=0.24-0.57; p≤0.001)., Conclusion: The nodal ratio and number of positive nodes seem to have a high prognostic impact in patients with HNSCC and can be of value in identifying patients at high risk who warrant more aggressive therapy., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Oropharyngeal sensitivity plays a vital role in the initiation of the swallowing reflex and is thought to decline as part of the aging-process. Taste and smell functions appear to decline with age as well. The aim of our study was to generate data of oral sensitivity in healthy participants for future studies and to analyse age-related changes and their interdependence by measuring oral sensitivity, taste, and smell function. The experiment involved 30 participants younger than and 30 participants older than 60. Sensitivity threshold as a surrogate of oral sensitivity was measured at the anterior faucial pillar by electrical stimulation using commercially available pudendal electrode mounted on a gloved finger. Smell and taste were evaluated using commercially available test kits. Mean sensitivity was lower in young participants compared to older participants (1.9 ± 0.59 mA vs. 2.42 ± 1.03 mA; p = 0.021). Young participants also performed better in smell (Score 11.13 ± 0.86 vs 9.3 ± 1.93; p < 0.001) and taste examinations (Score 11.83 ± 1.86 vs 8.53 ± 3.18; p < 0.001). ANCOVA revealed a statistical association between sensitivity and smell (p = 0.08) that was moderated by age (p = 0.044). Electrical threshold testing at the anterior faucial pillar is a simple, safe, and accurate diagnostic measure of oral sensitivity. We detected a decline of oral sensitivity, taste, and smell in older adults.Trial registration: Clinicaltrials.gov, NCT03240965. Registered 7th August 2017- https://clinicaltrials.gov/ct2/show/NCT03240965 ., (© 2022. The Author(s).)

Dysphagia is common in neurological disease. However, our understanding of swallowing and its central nervous control is limited. Sensory information plays a vital role in the initiation of the swallowing reflex and is often reduced in stroke patients. We hypothesized that the sensitivity threshold of the anterior faucial pillar could be facilitated by either electrical stimulation (ES) or taste and smell information. The sensitivity threshold was measured by ES in the anterior faucial pillar region. The measurement was repeated 5 min after baseline. Thirty minutes after baseline, the participants underwent a test for taste and smell. Immediately after the test, the ES was repeated. Thirty healthy volunteers with a mean age of 27 ± 5.1 participated in the trial. Mean sensitivity threshold at baseline was 1.9 ± 0.59 mA. The values 5 min after baseline (1.74 ± 0.56 mA, p = 0.027) and 30 min after baseline (1.67 ± 0.58 mA, p = 0.011) were significantly lower compared to the baseline, but there was no difference between the latter (p = 0.321). After 5 min, a potentially facilitating effect was found on oral sensitivity by ES of the faucial pillar area. Thirty minutes later, this effect was still present.Trial registration Clinicaltrials.gov, NCT03240965. Registered 7th August 2017- https://clinicaltrials.gov/ct2/show/NCT03240965 .

(1) Purpose: Comprehensive geriatric care (CGC) is a multidisciplinary treatment approach for elderly patients. We aimed to investigate outcomes in fracture patients who had been treated using this approach in a large geriatric unit. (2) Methods: This observational cohort study assessed the gait function (using the Tinetti Balance and Gait Test (TBGT)) and basic activities of daily living (ADL) (using the Barthel index (BI)) before and after CGC and compared the results. Baseline data, walking ability assessments (Timed Up and Go, TUG), and cognitive status (mini mental status examination, MMSE) were also analyzed in the subgroup of patients with versus without fractures. (3) Results: Out of 1263 hospitalized patients, 1099 received CGC (median age: 83.1 years (IQR: 79.0-87.8 years); 64.1% were female). TBGT improvement was observed in 90.7% and BI increased in 82.7% of fracture patients. A TBGT improvement of >5 was noted in 47.3% and was associated with female sex, a lower BI at admission (median: 40 versus 45; p = 0.010), and poorer mobility on admission (TUG: median 5 versus 4; p = 0.001). An improvement in BI of ≥15 was observed in 63.0% of the cases, and was associated with a better cognitive status (MMSE: median 25 versus 18; p = 0.001) and inversely associated with diabetes mellitus and a previous stroke. (4) Conclusion: CGC in specialized geriatric units improves the balance and gait and the basic ADL in geriatric patients. After fracture, female patients are more likely to experience improvements in gait and balance, while patients with better cognitive condition are more likely to experience improvements in ADL.

Purpose: Dysphagia is common in critically ill neurological patients and is associated with a high mortality and morbidity. Data on the usefulness of flexible endoscopic examination of swallowing (FEES) in neurological intensive care unit (ICU) patients are lacking, raising the need for evaluation., Method: FEES was performed in neurological intensive care patients suspected of dysphagia. We correlated findings with baseline data, disability status, pneumonia and duration of hospitalisation, as well as a need for mechanical ventilation or tracheotomy., Result: This analysis consisted of 125 patients with suspected dysphagia. Most of the patients (81; 64,8%) suffered from acute stroke. Dysphagia was diagnosed using FEES in 90 patients (72%). FEES results led to dietary modifications in 80 patients (64%). The outcome at discharge was worse in dysphagic stroke patients diagnosed by FEES as compared to non-dysphagic stroke patients ( p  = 0.009). Patients without oral diet had higher need for intubation ( p  = 0.007), tracheotomy ( p  = 0.032) and higher mortality ( p  < 0.001) in comparison to patients with at least small amounts of oral intake., Conclusion: As the clinical assessment of the patients often classified the dysphagia incorrectly, the broad use of FEES in ICU patients might help to adequately adjust patients' oral diet. This knowledge might contribute to lower mortality and morbidity.

Objective: With a combination of different sympathetic tests, we aimed to elucidate whether impairment of sympathetic function in Parkinson's disease (PD) is the consequence of a central or peripheral efferent dysfunction., Methods: Thirty-five patients with early-to-intermediate PD (median age: 63 years; IQR: 57-67 years; disease duration 1-9 years, 15 women) and 20 age- and sex-matched healthy controls (median age: 64.5 years; IQR: 58-68 years; 10 women) were recruited. Autonomic testing was performed in two subgroups and included the assessment of resting cardiovascular parameters, postprandial hypotension (PPH), orthostatic hypotension (OH), and vasoconstriction induced by intradermal microdialysis with different concentrations of norepinephrine (NE; 10 -5 ; 10 -6 ; 10 -7 ; 10 -8 ) and by cold through forehead cooling. We also used sympathetic multiunit microneurography (muscle sympathetic nerve activity; MSNA; burst frequency (BF): bursts per minute; burst incidence (BI): bursts per 100 heart beats) and evaluated the presence of phosphorylated α-synuclein deposits in skin innervation in biopsies from the thighs by immunohistohemistry., Results: Diastolic blood pressure was higher in the PD group at rest (p < .001) and during OH (F = 6.533; p = .022). Vasoconstriction induced by NE microdialysis and cold was unchanged in PD patients. MSNA was lower in PD patients than in controls (BF: p = .001; BI: p = .025). Phosphorylated α-synuclein deposits could be found only in PD patients., Conclusion: We did not find indications for peripheral sympathetic nerve fiber dysfunction or adrenoreceptor sensitivity changes. The decreased MSNA argues in favor of central sympathetic impairment., (© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Background: Diagnosing dysphagia in acute stroke patients is crucial, as this comorbidity determines morbidity and mortality; we therefore investigated the impact of flexible nasolaryngeal endoscopy (FEES) in acute stroke patients., Methods: The FEES investigation as performed in acute stroke patients treated at a large university hospital, allocated as a standard procedure for all patients suspected of dysphagia. We correlated our findings with baseline data, disability status, pneumonia, duration of hospitalisation, necessity for mechanical ventilation and treatment on the intensive care unit. The study was designed as a cross-sectional hospital-based registry., Results: We investigated 152 patients. The median age was 73; 94 were male. Ischemic stroke was diagnosed in 125 patients (82.2%); 27 (17.8%) suffered intracerebral haemorrhage. Oropharyngeal dysphagia was diagnosed in 72.4% of the patients, and was associated with higher stroke severity on admission (median NIHSS 11 [IQR 6-17] vs. 7 [4-12], p = .013; median mRS 5 [IQR 4-5] vs. 4 [IQR 3-5], p = .012). Short-term mortality was higher among patients diagnosed with dysphagia (7.2% vs. 0%, p = .107). FEES examinations revealed that only 30.9% of the patients had an oral diet appropriate for their swallowing abilities. A change of oral diet was associated with a better outcome at discharge (mRS; p = .006), less need of mechanical ventilation (p = .028), shorter period of hospitalisation (p = .044), and lower rates of pneumonia (p = .007) and mortality (p = .011)., Conclusion: Due to the inability of clinical assessments to detect silent aspiration, FEES might be better suited to identify stroke patients at risk and may contribute to a better functional outcome and lower rates of pneumonia and mortality. Our findings also point to a low awareness of dysphagia, even in a specialised stroke centre. FEES in acute stroke patients helps to adjust the oral diet for the vast majority of stroke patients (69.1%) based on their swallowing abilities, potentially avoiding severe complications.

In most vertebrates, including zebrafish, the hypothalamic serotonergic cerebrospinal fluid-contacting (CSF-c) cells constitute a prominent population. In contrast to the hindbrain serotonergic neurons, little is known about the development and function of these cells. Here, we identify fibroblast growth factor (Fgf)3 as the main Fgf ligand controlling the ontogeny of serotonergic CSF-c cells. We show that fgf3 positively regulates the number of serotonergic CSF-c cells, as well as a subset of dopaminergic and neuroendocrine cells in the posterior hypothalamus via control of proliferation and cell survival. Further, expression of the ETS-domain transcription factor etv5b is downregulated after fgf3 impairment. Previous findings identified etv5b as critical for the proliferation of serotonergic progenitors in the hypothalamus, and therefore we now suggest that Fgf3 acts via etv5b during early development to ultimately control the number of mature serotonergic CSF-c cells. Moreover, our analysis of the developing hypothalamic transcriptome shows that the expression of fgf3 is upregulated upon fgf3 loss-of-function , suggesting activation of a self-compensatory mechanism. Together, these results highlight Fgf3 in a novel context as part of a signalling pathway of critical importance for hypothalamic development., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

Background New evidence regarding stroke prevention in atrial fibrillation has been published. Implementing knowledge into clinical practice remains challenging. Aims To investigate oral anticoagulants in stroke patients documented in a nationwide registry. Methods The database is an obligatory federal-state-wide hospital-based registry that covers more than 95% of all ischemic strokes, transient ischemic attacks and intracerebral hemorrhages in a community of more than six million inhabitants (Hesse/Germany). We analyzed oral anticoagulants prescribed on discharge in patients with stroke or transient ischemic attack during 2006-2015. Results From 2006 to 2015, we annually selected median 20,895 patients. From 2006 to 2015, the proportion of patients treated with oral anticoagulants increased (9.8% to 24%). The annual proportion of patients with atrial fibrillation remained constant (median: 23%). In atrial fibrillation patients treated with oral anticoagulants, the age increased (median 2008/2009: 76.9 years vs. 2014/2015 79.4 years). The percentage of treated individuals in atrial fibrillation increased dramatically (2006: 30.1% to 2015: 74.5%); in 2015, 30.8% of these patients received vitamin K antagonists and 70.2% new oral anticoagulants. Independent factors associated with new oral anticoagulants therapy were a previous medication with new oral anticoagulants and a treatment on stroke unit. Between new oral anticoagulants- and vitamin K antagonists-treated patients (2015), no differences in age were noted (both mean: 79.4 years). Conclusions The new oral anticoagulants availability enhanced a general trend treating more target patients with oral anticoagulants.

Objectives: Fibre-endoscopic evaluation of swallowing (FEES) to detect dysphagia is gaining more and more importance as a diagnostic tool. Therefore, we have investigated the impact of FEES in neurological patients in a clinical setting., Design: Cross-sectional hospital-based registry., Setting: Primary acute care in a neurological department of a German university hospital., Participants: 241patients with various neurological diseases who underwent FEES procedure., Primary and Secondary Outcome Measures: Dysphagia and related comorbidities., Results: 267 FEES were performed in 241 patients with various neurological diagnoses. Dysphagia was diagnosed in 68.9% of the patients. In only 33.1% of the patients, appropriate oral diet was chosen prior to FEES. A relevant dysphagia occurred more often in patients with structural brain lesions (83.1% vs 65.3%, P=0.001), patients with dysphagia had a longer hospitalisation (median 18 (IQR 12-30) vs 15 days (IQR 9.75-22.75), P=0.005) and had a higher mortality (8.4% vs 1.3%, P=0.041). When the oral diet was changed, we observed a lower pneumonia rate (36% vs 50%, P=0.051) and a lower mortality (3.7% vs 11.3%, P=0.043) in comparison to no change of oral diet. A restriction of oral diet was identified more often in older patients (median 75 years (IQR 66.3-82 years) vs median 72 years (IQR 60-79 years), P=0.01) and in patients with structural brain lesions (86.8% vs 73.1%, P=0.05)., Conclusion: On clinical investigation, dysphagia was misjudged for the majority of the patients. FEES might help to compensate this drawback, revising the diet regime in nearly 70% of the patients., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: The aim of the study was to report physician experience-based "real-world" treatment patterns with botulinum toxin type A in patients with stroke and traumatic brain injury., Design: A prospective, multicenter, international observational registry design was used., Results: Six hundred twenty-seven participants with stroke and 132 participants with traumatic brain injury were assessed and treated by 17 more experienced physicians and 12 less experienced physicians. Due to the limited usage of abobotulinumtoxinA Dysport and incobotulinumtoxinA Xeomin, data were reported on onabotulinumtoxinA BOTOX only. Based on physician experience, onabotulinumtoxinA doses were statistically different with larger mean doses injected by more experienced physicians in the upper limb (59.9 [39.0], P = 0.001) and in the lower limb (101.8 [69.2], P < 0.001). Treated deformities significantly differed for both upper limb and lower limb (P < 0.001). More experienced physicians showed a larger mean change in Ashworth Scale scores from baseline for the equinovarus/equinus foot and stiff knee (P = 0.001 and 0.03). Less experienced physicians showed a larger mean change in Ashworth Scale scores from baseline for the adducted thigh (P = 0.05). Less experienced physicians had statistically significant larger change in hand pain scores for clenched fist deformity treatment at follow-up compared with more experienced physicians (P = 0.01). Physician experience demonstrated a significant difference on patients reported satisfaction toward their secondary goal with higher scores for more experienced physician (P = 0.04)., Conclusions: This international registry provides clinical nuances of treatment based on physician clinical experience in a robust sample size.

Background: Visualisation of nigrosome 1, a substructure of the healthy substantia nigra, was restricted in susceptibility weighted MR imaging in almost all patients with Parkinson's disease studied so far. The purpose of this study was to determine the degree of visibility of this substructure in subjects without Parkinson's disease and to examine the potential link between increasing brain iron accumulation with age and its detectability., Methods: In 46 subjects (21 women, 25 men; 19 to 75 y; mean age: 44.5; SD: 15.6) examined with susceptibility weighted MR imaging at 7T visibility of nigrosome 1 was rated and classified. We assessed differences related to age and to signal intensities in the substantia nigra, red nucleus and putamen as correlates of the individual iron concentration., Results: In 93% nigrosome 1was at least unilaterally clearly present. In 24% at least one-sided limited visibility was observed. Using predefined classification criteria the specificity of the visibility across all age groups reached approximately 94%. We found no correlation with increasing iron concentrations with age., Conclusion: Aging with a related increase in iron concentration probably does not affect the visibility of nigrosome 1 at 7T SWI MRI. Our results support the role of this feature as a future differential diagnostic tool but further large-scale prospective studies are needed to better define the extent of a "limited visibility" to which an individual can be considered healthy.

First line pain relief medication during pregnancy relies nearly entirely on the over-the-counter analgesic acetaminophen, which is generally considered safe to use during gestation. However, recent epidemiological studies suggest a risk of developing attention-deficit/hyperactivity disorder (ADHD)-like symptoms in children if mothers use acetaminophen during pregnancy. Currently, there are no experimental proofs that prenatal acetaminophen exposure causes developmental brain alterations of progeny. Exposure to high acetaminophen concentrations causes liver toxicity, which is well investigated in different model organisms. However, sub-liver-toxic concentrations have not been experimentally investigated with respect to ADHD endophenotypes such as hyperactivity. We used zebrafish to investigate the potential impact of acetaminophen exposure on locomotor activity levels, and compared it to the established zebrafish Latrophilin 3 (Lphn3) ADHD-model. We determined the sub-liver-toxic concentration of acetaminophen in zebrafish larvae and treated wild-type and lphn3.1 knockdown larvae with increasing concentrations of acetaminophen. We were able to confirm that lphn3.1 knockdown alone causes hyperactivity, strengthening the implication of Lphn3 dysfunction as an ADHD risk factor. Neither acute nor chronic exposure to acetaminophen at sub-liver-toxic concentrations in wild-type or lphn3.1 knock-downs increases locomotor activity levels. Together our findings show that embryonic to larval exposure to acetaminophen does not cause hyperactivity in zebrafish larvae. Furthermore, there are no additive and/or synergistic effects of acetaminophen exposure in a susceptible background induced by knock-down of lphn3.1. Our experimental study suggests that there is, at least in zebrafish larvae, no direct link between embryonic acetaminophen exposure and hyperactivity. Further work is necessary to clarify this issue in humans.