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Background and purpose: Protein tyrosine phosphatase receptor type Q (PTPRQ) was extracted from the cerebrospinal fluid (CSF) of patients with probable idiopathic normal‐pressure hydrocephalus (iNPH) by proteome analysis. We aimed to assess the feasibility of using CSF PTPRQ concentrations for the additional diagnostic criterion of iNPH in Japanese and Finnish populations. Methods: We compared PTPRQ concentrations among patients with probable iNPH and neurologically healthy individuals (normal control [NC] group), patients with normal‐pressure hydrocephalus (NPH) of acquired and congenital/developmental aetiologies, patients with Alzheimer's disease and patients with Parkinson's disease in a Japanese analysis cohort. A corresponding iNPH group and NC group in a Finnish cohort was used for validation. Patients in the Finnish cohort who underwent biopsy were classified into two groups based on amyloid and/or tau deposition. We measured PTPRQ expression levels in autopsied brain specimens of iNPH patients and the NC group. Results: Cerebrospinal fluid PTPRQ concentrations in the patients with NPH of idiopathic, acquired and congenital/developmental aetiologies were significantly higher than those in the NC group and those with Parkinson's disease, but iNPH showed no significant differences when compared with those in the Alzheimer's disease group. For the patients with iNPH, the area under the receiver‐operating characteristic curve was 0.860 in the Japanese iNPH and 0.849 in the Finnish iNPH cohorts. Immunostaining and in situ hybridization revealed PTPRQ expression in the ependymal cells and choroid plexus. It is highly possible that the elevated PTPRQ levels in the CSF are related to ependymal dysfunction from ventricular expansion. Conclusions: Cerebrospinal fluid PTPRQ levels indicated the validity of this assay for auxiliary diagnosis of adult chronic hydrocephalus. [ABSTRACT FROM AUTHOR]

The identification of pollen plays an important role in ecology, palaeo-climatology, honey quality control and other areas. Currently, expert knowledge and reference collections are essential to identify pollen origin through light microscopy. Pollen identification through molecular sequencing and DNA barcoding has been proposed as an alternative approach, but the assessment of mixed pollen samples originating from multiple plant species is still a tedious and error-prone task. Next-generation sequencing has been proposed to avoid this hindrance. In this study we assessed mixed pollen probes through next-generation sequencing of amplicons from the highly variable, species-specific internal transcribed spacer 2 region of nuclear ribosomal DNA. Further, we developed a bioinformatic workflow to analyse these high-throughput data with a newly created reference database. To evaluate the feasibility, we compared results from classical identification based on light microscopy from the same samples with our sequencing results. We assessed in total 16 mixed pollen samples, 14 originated from honeybee colonies and two from solitary bee nests. The sequencing technique resulted in higher taxon richness (deeper assignments and more identified taxa) compared to light microscopy. Abundance estimations from sequencing data were significantly correlated with counted abundances through light microscopy. Simulation analyses of taxon specificity and sensitivity indicate that 96% of taxa present in the database are correctly identifiable at the genus level and 70% at the species level. Next-generation sequencing thus presents a useful and efficient workflow to identify pollen at the genus and species level without requiring specialised palynological expert knowledge. [ABSTRACT FROM AUTHOR]

Background: Chronic subdural haematoma is a common surgically treated intracranial emergency. Burr-hole drainage surgery, to evacuate chronic subdural haematoma, involves three elements: creation of a burr hole for access, irrigation of the subdural space, and insertion of a subdural drain. Although the subdural drain has been established as beneficial, the therapeutic effect of subdural irrigation has not been addressed., Methods: The FINISH trial was an investigator-initiated, pragmatic, multicentre, nationwide, randomised, controlled, parallel-group, non-inferiority trial in five neurosurgical units in Finland that enrolled adults aged 18 years or older with a chronic subdural haematoma requiring burr-hole drainage. Patients were randomly assigned (1:1) by computer-generated block randomisation with block sizes of four, six, or eight, stratified by site, to burr-hole drainage either with or without subdural irrigation. All patients and staff were masked to treatment assignment apart from the neurosurgeon and operating room staff. A burr hole was drilled at the site of maximum haematoma thickness in both groups, and the subdural space was either irrigated or not irrigated before inserting a subdural drain, which remained in place for 48 h. Reoperations, functional outcome, mortality, and adverse events were recorded for 6 months after surgery. The primary outcome was the reoperation rate within 6 months. The non-inferiority margin was set at 7·5%. Key secondary outcomes that were also required to conclude non-inferiority were the proportion of participants with unfavourable functional outcomes (ie, modified Rankin Scale score of 4-6, where 0 indicates no symptoms and 6 indicates death) and mortality rate at 6 months. The primary and key secondary analyses were done in both the intention-to-treat and per-protocol populations. The trial was registered with ClinicalTrials.gov (NCT04203550) and is completed., Findings: From Jan 1, 2020, to Aug 17, 2022, we assessed 1644 patients for eligibility and 589 (36%) patients were randomly assigned to a treatment group and treated (294 assigned to drainage with irrigation and 295 assigned to drainage without irrigation; 165 [28%] women and 424 [72%] men). The 6-month follow-up period extended until Feb 14, 2023. In the intention-to-treat analysis, 54 (18·3%) of 295 participants required reoperation in the group assigned to receive no irrigation versus 37 (12·6%) of 294 in the group assigned to receive irrigation (difference of 6·0 percentage points, 95% CI 0·2-11·7; p=0·30; adjusted for study site). There were no significant between-group differences in the proportion of people with modified Rankin Scale score of 4-6 (37 [13·1%] of 283 in the no-irrigation group vs 36 [12·6%] of 285 in the irrigation group; p=0·89) or mortality rate (18 [6·1%] of 295 in the no-irrigation group vs 21 [7·1%] of 294 in the irrigation group; p=0·58). The findings of the primary intention-to-treat analysis were not materially altered in the per-protocol analysis. There were no significant between-group differences in the number of adverse events, and the most frequent severe adverse events were systemic infections (26 [8·8%] of 295 participants who did not receive irrigation vs 22 [7·5%] of 294 participants who received irrigation), intracranial haemorrhage (13 [4·4%] vs seven [2·4%]), and epileptic seizures (five [1·7%] vs nine [3·1%])., Interpretation: We could not conclude non-inferiority of burr-hole drainage without irrigation. The reoperation rate was 6·0 percentage points higher after burr-hole drainage without subdural irrigation than with subdural irrigation. Considering that there were no differences in functional outcome or mortality between the groups, the trial favours the use of subdural irrigation., Funding: State Fund for University Level Health Research (Helsinki University Hospital), Finska Läkaresällskapet, Medicinska Understödsföreningen Liv och Hälsa, and Svenska Kulturfonden., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objective: The aim was to study the outcome and complications of operative treatment for subaxial cervical spine injuries with respect to injury morphology and surgical strategy., Methods: A population-based cohort of 271 consecutive patients treated at Kuopio University Hospital from 2003 to 2018 was retrospectively reviewed., Results: The mean age was 52.4 (range 12-90) years and 78.6% were male. The AOSpine morphological classification was C in 56.5%, B in 24.7% and A in 17.0% of cases. The surgical approach was anterior in 70.8%, posterior in 20.3% and combined in 8.9% of patients. Fixation alignment was maintained in 96.9% of patients. Instrumentation failures were observed only in patients operated anteriorly but no statistical difference was found between the surgical approaches. The American Spinal Injury Association Impairment Scale (AIS) grade improved in 22.1% of patients. Patients with preoperative AIS grade C had significant potential for neurological improvement (OR 10.44; 95% CI 1.77-61.56; p  = 0.010). Postoperative, mostly mild, complications manifested in 22.5% of patients. The posterior approach was associated with fewer postoperative complications (OR 0.18; 95% CI 0.06-0.51; p  = 0.001). Preoperative AIS grade A was a significant predisposing factor for complications (OR = 4.90; 95% CI = 1.49-16.10; p  = 0.009). The perioperative (90-day) mortality rate was 3.3%. The mean follow-up period was 64.7 ± 25.9 (radiological)/136.7 ± 174.8 (clinical) days., Conclusions: Operative treatment is safe and effective but the surgical approach should be patient- and injury-specific. The prognosis for neurological recovery from spinal cord injury is superior in patients with partially preserved motor function., Competing Interests: The authors have no conflicts of interest. This study was approved by the Ethics Committee of KUH District, Kuopio, Finland (permission number 236/2017). Due to the retrospective nature of the study no informed consent was required., (© 2024 The Authors.)

Study Design: A register-based retrospective series and a systematic review of literature., Objectives: Tarlov cysts are meningeal cysts typically found in the sacral region. They have a dualistic nature ranging from an incidental finding to a symptomatic pathology. There are no established treatment protocols and predictors of operative outcome. Therefore, we aimed to study the outcome of surgical treatment for Tarlov cysts and to characterize patient-, and treatment-related factors predicting outcomes., Methods: A systematic review of previous literature was performed and a retrospective cohort of all patients operated on for Tarlov cysts at BLINDED between 1995 and 2020 was collected. Patient records were evaluated along with radiological images., Results: Ninety-seven consecutive patients were identified with follow-up data available for 96. Improvement of symptoms after surgery was observed in 76.0% of patients (excellent or good patient-reported outcome) and the complication rate was 17.5%. Sacral or lower back pain as a preoperative symptom was associated with improvement after surgery ( P = .007), whereas previous lower back surgery was more common in patients who did not benefit from surgery ( P = .034). No independent predictors of outcome were identified in a regression analysis., Conclusions: This is the second-largest study on the treatment of Tarlov cysts ever published. Operative treatment in a selected patient population will likely produce improvement in the symptoms when balanced with the complication rate and profile of surgery. Preoperative lower back or sacral pain is a potential indicator for improvement after surgery., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: In the field of mental health, religiosity and spirituality have gained particular attention in recent decades. However, only a few studies to date have investigated the effects of different types of religiosity and spirituality. In association with the recent introduction of a Swedish version of the multidimensional inventory of religious/spiritual well-being (MI-RSWB-S), the present study aimed to identify possible types of Religious/Spiritual Well-Being by using cluster analyses and to examine the extracted groups for differences in the sense of coherence (SOC), the Big Five personality factors, and central aspects of religiosity. Additionally, the study design was intended to further contribute to the validation of the MI-RSWB-S., Methods: Based on a convenience sample of Swedish students ( N  = 1,011), initially obtained for the development of the MI-RSWB-S, the study included the MI-RSWB-S, the 13-items sense of coherence scale, the 10-item personality inventory, and the centrality of religiosity scale. For the statistical analysis, cluster analyses and one-way analyses of variance (ANOVAs) were conducted., Results: The cluster analyses yielded the following four groups: Religiosity and spirituality high ( n  = 124), religiously oriented ( n  = 200), spiritually oriented ( n  = 149), and religiosity and spirituality low ( n  = 538). The groups differed in most aspects of well-being, in the personality dimensions agreeableness and openness to experience, as well as in central aspects of religiosity. In contrast, no differences were found for SOC, extraversion, conscientiousness, and emotional instability., Conclusion: Our results suggest that different types of religious/spiritual well-being are associated with mental health and personality dimensions in substantially different ways, thus offering an interesting potential for future research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Podolin-Danner, Wenzl, Knorr, Fuchshuber, Silani and Unterrainer.)

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a multifactorial disease presenting with a classical symptom triad of cognitive decline, gait disturbance and urinary incontinence. The symptoms can be alleviated with shunt surgery but the etiology of the symptoms remains unclear. Navigated transcranial magnetic stimulation (nTMS) was applied to characterize corticospinal excitability and cortical motor function before and after shunt surgery in order to elucidate the pathophysiology of iNPH. We also aimed to determine, whether nTMS could be applied as a predictive tool in the pre-surgical work-up of iNPH., Methods: 24 patients with possible or probable iNPH were evaluated at baseline, after cerebrospinal fluid drainage test (TAP test) and three months after shunt surgery (follow-up). Symptom severity was evaluated on an iNPH scale and with clinical tests (walking test, Box & Block test, grooved pegboard). In the nTMS experiments, resting motor threshold (RMT), silent period (SP), input-output curve (IO-curve), repetition suppression (RS) and mapping of cortical representation areas of hand and foot muscles were assessed., Results: After shunt surgery, all patients showed improved performance in gait and upper limb function. The nTMS parameters showed an increase in the RMTs (hand and foot) and the maximum value of the IO-curve increased in subject with a good surgical outcome. The improvement in gait correlated with an increase in the maximum value of the IO-curve. SP, RS and mapping remained unchanged., Conclusion: The excitability of the motor cortex and the corticospinal tract increased in iNPH patients after shunt surgery. A favorable clinical outcome of shunt surgery is associated with a higher ability to re-form and maintain neuronal connectivity., (© 2022. The Author(s).)

Purpose: To study the effect of antithrombotic therapy (ATT) on the outcome of operatively treated chronic subdural hematomas (CSDH)., Methods: A retrospective population-based cohort study from Eastern Finland including all adult patients who underwent a burr-hole craniostomy (BHC) for CSDH during 2016 and 2017. The follow-up time for recurrence was 6 months and for mortality 3 years., Results: A total of 301 CSDH patients were included in the study. ATT (antithrombotic therapy; antiplatelet or anticoagulant medication) was used by 164 patients (54.5%) at the time of diagnosis. The hematoma was bilateral in 102 patients (33.9%). Forty-seven patients (15.8%) encountered hematoma recurrence. Bilateral CSDHs required reoperations more often than unilateral hematomas (12.6% vs. 22.0%; p = 0.036) regardless of the primary operation (uni- or bilateral). A bivariate logistic regression analysis showed that bilateral hematoma (OR 1.918; 95% CI 1.013-3.630; p = 0.045) and male gender (OR 2.363; 95% CI 1.089-5.128; p = 0.030) independently predicted hematoma recurrence. The overall three-year mortality was 27.9%. The use of ATT was not associated with CSDH recurrence, and the length of the temporary postoperative ATT discontinuation did not correlate with the rate of thromboembolic events., Conclusions: ATT did not affect CSDH recurrence in our study population, and the duration of the temporary postoperative ATT discontinuation was not associated with the rate of thromboembolic complications. Male gender and bilateral hematomas were more frequently associated with recurrences., (© 2022. The Author(s).)

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a clinico-radiological syndrome of elderly individuals likely sustained by different neurodegenerative changes as copathologies. Since iNPH is a potentially reversible condition, assessing neurodegenerative pathologies in vitam through CSF biomarkers and their influence on clinical features and surgical outcome represents crucial steps., Methods: We measured α-synuclein seeding activity related to Lewy body (LB) pathology by the real-time quaking-induced conversion assay (RT-QuIC) and Alzheimer disease core biomarkers (proteins total-tau, phospho-tau, and amyloid-beta) by immunoassays in the cerebrospinal fluid (CSF) of 293 iNPH patients from two independent cohorts. To compare the prevalence of LB copathology between iNPH participants and a control group representative of the general population, we searched for α-synuclein seeding activity in 89 age-matched individuals who died of Creutzfeldt-Jakob disease (CJD). Finally, in one of the iNPH cohorts, we also measured the CSF levels of neurofilament light chain protein (NfL) and evaluated the association between all CSF biomarkers, baseline clinical features, and surgery outcome at 6 months., Results: Sixty (20.5%) iNPH patients showed α-synuclein seeding activity with no significant difference between cohorts. In contrast, the prevalence observed in CJD was only 6.7% (p = 0.002). Overall, 24.0% of iNPH participants showed an amyloid-positive (A+) status, indicating a brain co-pathology related to Aβ deposition. At baseline, in the Italian cohort, α-synuclein RT-QuIC positivity was associated with higher scores on axial and upper limb rigidity (p = 0.003 and p = 0.011, respectively) and lower MMSEc scores (p = 0.003). A+ patients showed lower scores on the MMSEc (p = 0.037) than A- patients. Higher NfL levels were also associated with lower scores on the MMSEc (rho = -0.213; p = 0.021). There were no significant associations between CSF biomarkers and surgical outcome at 6 months (i.e. responders defined by decrease of 1 point on the mRankin scale)., Conclusions: Prevalent LB- and AD-related neurodegenerative pathologies affect a significant proportion of iNPH patients and contribute to cognitive decline (both) and motor impairment (only LB pathology) but do not significantly influence the surgical outcome at 6 months. Their effect on the clinical benefit after surgery over a more extended period remains to be determined., (© 2022. The Author(s).)

Introduction: The Accreditation Council for Graduate Medical Education and the American Board of Psychiatry and Neurology first developed milestones for the clinical neurophysiology (CNP) fellowship in 2015. The milestones provide a comprehensive evaluation of the fellow's development based on six domains of competency. Here, we describe the development of a new set of milestones for CNP fellowship with level 1 as the incoming level, level 4 as the goal for graduation, and level 5 as the aspirational level that may not be achieved., Methods: Committee members were nominated or volunteered to participate in the milestones update. Milestone development began with the creation of a shared mental model of the ideal skills and knowledge a graduating CNP fellow should attain., Results: The CNP committee met virtually 7 times for a total of 14 meeting hours. Nine Patient Care and five Medical Knowledge milestones evolved from the seven Patient Care and six Medical Knowledge milestones that were in the first iteration. The committee incorporated 11 "Harmonized Milestones" into the revision and a supplemental guide was created., Conclusions: The revised Accreditation Council for Graduate Medical Education milestones for CNP fellowship contain important updates that program directors should review against their curricula to identify any gaps in learning. Program leadership should take note of two new Patient Care milestones for telemedicine and intraoperative monitoring. Clinical neurophysiology fellowships are not designed to provide level 4 competency across all milestones. The revised milestones should be viewed within the context of an individual program's goals., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 by the American Clinical Neurophysiology Society.)

Background: Studies investigating the relationship between religiosity/spirituality and mental health have suggested both positive and negative associations, highlighting the importance of multifaceted assessment of these rather broad constructs. The present study aims at contributing to this field of research by providing a validated Swedish version of the Multidimensional Inventory for Religious/Spiritual Well-Being (MI-RSWB-S) and further examining how this instrument relates to Big Five personality factors, Sense of Coherence (SOC), and religiosity. Methods: Data were collected from a total of 1,011 Swedish students (747 females; age range 18-40) via completion of an online survey, including a new Swedish Version of the MI-RSWB-S, the Ten Item Personality Inventory (TIPI), the Sense of Coherence Scale (SOC-13), and the Centrality of Religiosity Scale (CRS-5). Results: Results revealed adequate estimates of internal consistency and substantial evidence for the postulated six-dimensional structure. However, confirmatory factor analysis yielded poor fit indices, resulting in the development and validation of a revised measure of Religious/Spiritual Well-Being (RSWB), comprising the subscales General Religiosity and Connectedness. Most of the MI-RSWB-S dimensions were positively correlated with the personality domains Extraversion, Openness to Experience, Conscientiousness, and Agreeableness and negatively related to Neuroticism. SOC was positively linked to Hope Immanent, Forgiveness, Hope Transcendent, and Experiences of Sense of Meaning, whereas CRS exhibited positive correlations with all MI-RSWB-S subscales except Hope Transcendent. Conclusion: The findings of the current study support the validity and reliability of the Swedish adoption of the MI-RSWB and confirm previously reported associations with the Big Five personality traits, SOC, and CRS. More in general, our results underline the putative substantial link between RSWB dimensions and mental health. Further research especially in clinical surroundings as well as by employing more representative samples is now warranted., Competing Interests: The reviewer HB-C declared a shared affiliation, with one of the authors H-FU to the handling editor at the time of the review. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wenzl, Fuchshuber, Podolin-Danner, Silani and Unterrainer.)

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease with a characteristic symptom triad of gait disturbance, cognitive decline, and incontinence. Recently, also dysfunctions in upper limbs have been described in iNPH and reported to improve after shunt surgery. We aim to describe the role of upper limb motor function in the clinical assessment of iNPH patients and its influence on activities of daily living (ADL)., Methods: Seventy-five consecutive patients with probable iNPH were studied pre-operatively and at 3 and 12 months after shunt surgery. The pre-operative evaluation included lumbar drainage of cerebrospinal fluid (tap test). Motor functions were assessed in upper and lower limbs with Grooved Pegboard Test (GPT), Box & Block Test (BBT), Total Score of Gait (TSG), and balance test. ADL was assessed with Barthel's index and cognition in accordance with the Consortium to Establish a Registry for Alzheimer's Disease (CERAD)., Results: Patients showed improvement in all motor tests and ADL at 3 months after shunt surgery. The improvement remained stable during the 12-month post-operative follow-up. The motor function tests correlated with each other and with ADL., Conclusions: A 3-month follow-up period after shunt surgery is adequate to show improvement in motor tasks, and a positive outcome will last for at least 12 months. A shunt-responsive dysfunction of upper limb motor performance plays a major role in ADL of iNPH patients. Therefore, we suggest an evaluation of upper limb motor performance to be included in routine evaluation of iNPH patients., (© 2021. The Author(s).)

Objective: To characterize surgical treatment and outcomes of C1 fractures in a population-based setup., Methods: Patients with C1 fracture treated at Kuopio University Hospital Neurosurgery were retrospectively identified from January 1996 to June 2017. C1 fractures were classified according to the AO Spine Upper Cervical and Gehweiler classification systems. Patients were divided into 4 groups based on their treatment: group 1 (underwent C1 surgery as a primary option), group 2 (underwent C1 surgery as a secondary option after initial nonoperative treatment), group 3 (underwent surgery involving the C1 level with main indication being a concomitant cervical spine fracture), and group 4 (C1 fracture treatment was nonoperative)., Results: We identified 47 patients with C1 fracture (mean age, 60.3 ± 18.2 years; 83.0% men; American Society of Anesthesiologists score, 2.3 ± 0.8). Concomitant cervical spine fractures were present in 89.4% of cases, most commonly in the C2 vertebra (75.4%). In group 2, 3 of 5 fractures changed from AO Spine type A to B in control imaging after nonoperative treatment, indicating fracture instability and requiring secondary surgery. Good C1 fracture alignment was achieved for 10 of 10 followed-up patients in groups 1 and 2, and for 10 of 11 followed-up patients in group 3. Residual neck pain and stiffness were present in all groups. Neurologic symptoms were rare and mild., Conclusions: For unstable C1 fractures, surgery is safe treatment with good outcomes. Fractures initially determined as stable may require surgery if alignment is worsened in follow-up imaging. Magnetic resonance imaging is recommended to better detect unstable C1 fractures in diagnostic imaging., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease with an unknown etiology. Disturbed corticospinal inhibition of the motor cortex has been reported in iNPH and can be evaluated in a noninvasive and painless manner using navigated transcranial magnetic stimulation (nTMS). This is the first study to characterize the immediate impact of cerebrospinal fluid (CSF) drainage on corticospinal excitability., Methods: Twenty patients with possible or probable iNPH (16 women and 4 men, mean age 74.4 years, range 67-84 years), presenting the classical symptom triad and radiological findings, were evaluated with motor function tests (10-m walk test, Grooved Pegboard and Box & Block test) and nTMS (silent period, SP, resting motor threshold, RMT and input-output curve, IO-curve). Evaluations were performed at baseline and repeated immediately after CSF drainage via lumbar puncture., Results: At baseline, iNPH patients presented shorter SPs (p < 0.001) and lower RMTs (p < 0.001) as compared to normative values. Positive correlation was detected between SP duration and Box & Block test (rho = 0.64, p = 0.002) in iNPH patients. CSF drainage led to an enhancement in gait velocity (p = 0.002) and a steeper IO-curve slope (p = 0.049)., Conclusions: Shorter SPs and lower RMTs in iNPH suggest impaired corticospinal inhibition and corticospinal hyperexcitability. The steeper IO-slope in patients who improve their gait velocity after CSF drainage may indicate a higher recovery potential. Corticospinal excitability correlated with the motor function of the upper limbs implying that the disturbance in motor performance in iNPH extends beyond the classically reported gait impairment.

Background: Vestibular schwannoma (VS) is a benign tumor originating from the vestibulocochlear nerve. The optimal treatment strategy is debated, since surgery may result in iatrogenic facial nerve injury. We report the results of VS surgery in a population-based unselected cohort in a center with access to Cyber Knife (CK) radiosurgery., Methods: We reviewed 117 consecutive operations and found 95 patients who had their primary operation due to vestibular schwannoma between 2001 and 2017. Facial nerve function was evaluated with the House-Brackmann (HB) scale and hearing with the EU classification., Results: The population consisted of 37 males and 58 females with a median age of 54 years (range 19-79). One year after surgery 67% of patients had a good outcome (HB 1-2). The rate of good outcome was 90% if no facial nerve damage was observed during intraoperative monitoring, the size of the tumor was under 30 mm and no hydrocephalus was present. During the study period, the treatment strategy changed from total to near-total resection after the introduction of CK radiosurgery, which could be used as a second-line treatment in case of residual tumor regrowth. This resulted in an improvement of outcomes (0% HB 5-6) despite the larger tumor sizes (25 ± 14 mm vs. 31 ± 9 mm, p < 0.05). Hearing preservation rates did not increase., Conclusions: Near-total resection and subsequent CK radiosurgery in case of residual tumor regrowth during follow-up seems to provide a good outcome of facial nerve function even in large VSs.

The availability of pollen in agricultural landscapes is essential for the successful growth and reproduction of honey bee colonies (Apis mellifera L.). The quantity and diversity of collected pollen can influence the growth and health of honey bee colonies, but little is known about the influence of landscape structure on pollen diet. In a field experiment, we rotated 16 honey bee colonies across 16 agricultural landscapes, used traps to collect samples of collected pollen and observed intra-colonial dance communication to gain information about foraging distances. DNA metabarcoding was applied to analyze mixed pollen samples. Neither the amount of collected pollen nor pollen diversity was related to landscape diversity. However, we found a strong seasonal variation in the amount and diversity of collected pollen in all sites independent of landscape diversity. The observed increase in foraging distances with decreasing landscape diversity suggests that honey bees compensated for lower landscape diversity by increasing their pollen foraging range in order to maintain pollen amount and diversity. Our results underscore the importance of a diverse pollen diet for honey bee colonies. Agri-environmental schemes aiming to support pollinators should focus on possible spatial and temporal gaps in pollen availability and diversity in agricultural landscapes.

Honey bees (Apis mellifera L.) show a large variation in foraging distances and use a broad range of plant species as pollen resources, even in regions with intensive agriculture. However, it is unknown how increasing areas of mass-flowering crops like oilseed rape (Brassica napus; OSR) or a decrease of seminatural habitats (SNH) change the temporal and spatial availability of pollen resources for honey bee colonies, and thus foraging distances and frequency in different habitat types. We studied pollen foraging of honey bee colonies in 16 agricultural landscapes with independent gradients of OSR and SNH area within 2 km and used waggle dances and digital geographic maps with major land cover types to reveal the distance and visited habitat type on a landscape level. Mean pollen foraging distance of 1347 decoded bee dances was 1015 m (± 26 m; SEM). In spring, increasing area of flowering OSR within 2 km reduced mean pollen foraging distances from 1324 m to only 435 m. In summer, increasing cover of SNH areas close to the colonies (within 200 m radius) reduced mean pollen foraging distances from 846 to 469 m. Frequency of pollen foragers per habitat type, measured as the number of dances per hour and hectare, was equally high for SNH, grassland, and OSR fields, but lower for other crops and forests. In landscapes with a small proportion of SNH a significantly higher density of pollen foragers on SNH was observed, indicating that pollen resources in such simple agricultural landscapes are more limited. Overall, we conclude that SNH and mass-flowering crops can reduce foraging distances of honey bee colonies at different scales and seasons with possible benefits for the performance of honey bee colonies. Further, mixed agricultural landscapes with a high proportion of SNH reduce foraging densities of honey bees in SNH and thus possible competition for pollen resources., (© 2016 by the Ecological Society of America.)

Background: Navigated transcranial magnetic stimulation (nTMS) has become established as an accurate noninvasive technique for mapping the functional motor cortex for the representation areas of upper and lower limb muscles but not yet for facial musculature., Objective: To characterize the applicability and clinical impact of using nTMS to map cortical motor areas of facial muscles in healthy volunteers and neurosurgical tumor patients., Methods: Eight healthy volunteers and 12 patients with tumor were studied. The motor threshold (MT) was determined for the abductor pollicis brevis and mentalis muscles. The lateral part of the motor cortex was mapped with suprathreshold stimulation intensity, and motor evoked potentials were recorded from several facial muscles. The patient protocol was modified according to the clinical indication., Results: In all healthy subjects, motor evoked potentials were elicited in the mentalis (mean latency, 13.4 milliseconds) and orbicularis oris (mean latency, 12.6 milliseconds) muscles. At 110% of MT of the mentalis, the motor evoked potentials of facial muscles were elicited mainly in the precentral gyrus but also from one gyrus anterior and posterior to it. The cortical areas applicable for mapping were limited by an artifact attributable to direct peripheral nerve stimulation. The mapping protocol was successful in 10 of 12 tumor patients at locating the representation area of the lower facial muscles. The MT of the facial muscles was significantly higher than that of the abductor pollicis brevis., Conclusion: nTMS is an applicable and clinically beneficial noninvasive method to preoperatively map the cortical representation areas of the facial muscles in the lower part of the face. Instead of using the MT of the abductor pollicis brevis, the stimulus intensity during mapping should be proportioned to the MT of a facial muscle.

Background: Unverricht-Lundborg disease (EPM1) is characterized by stimulus-sensitive and action-activated myoclonus, tonic-clonic seizures and ataxia. Several disease-related alterations in cortical structure and excitability have been associated with the motor symptoms of EPM1. This study aimed to elucidate possible alterations in cortical activation related to motor performance in EPM1., Methods: Fifteen EPM1-patients and 15 healthy volunteers matched for age and sex underwent motor functional MRI. Group differences in activations were evaluated in the primary and supplementary motor cortices and sensory cortical areas. Furthermore, in EPM1 patients, the quantitative fMRI parameters were correlated with the severity of the motor symptoms., Results: The EPM1-patients exhibited decreased activation in the left inferior frontal junction (IFJ) during right hand voluntary motor task when compared with controls. In the quantitative analysis, EPM1-patients had significantly weaker activation than controls in the hand knob and supplementary motor areas (SMA). The volume of activation in M1 decreased with age and duration of disease in the patient group, whereas the volume increased with age in controls. Negative correlations were observed between fMRI parameters of SMA and disease duration or age in patients but not in controls., Conclusions: The weaker motor fMRI activation observed in EPM1 patients parallels previous neurophysiological findings and correlates with the motor symptoms of the disease. Thus, the observed decrease in IFJ activation in EPM1 patients may be associated with the difficulties in initiation or termination of motor execution, a typical clinical symptom in EPM1. The fMRI findings reflect the progressive nature of this disease., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Unverricht-Lundborg disease is the most common form of progressive myoclonus epilepsies. In addition to generalized seizures, it is characterized by myoclonus, which usually is the most disabling feature of the disease. Classically, the myoclonus has been attributed to increased excitability of the primary motor cortex. However, inhibitory cortical phenomena have also been described along with anatomical alterations. We aimed to characterize the relationship between the excitability and anatomy of the motor cortex and their association with the severity of the clinical symptoms. Seventy genetically verified patients were compared with forty healthy controls. The symptoms were evaluated with the Unified Myoclonus Rating Scale. Navigated transcranial magnetic stimulation was applied to characterize the excitability of the primary motor cortex by determining the motor thresholds and cortical silent periods. In addition, the induced cortical electric fields were estimated using individual scalp-to-cortex distances measured from MRIs. A cortical thickness analysis was performed to elucidate possible disease-related anatomical alterations. The motor thresholds, cortical electric fields, and silent periods were significantly increased in the patients (P < 0.01). The silent periods correlated with the myoclonus scores (r = 0.48 to r = 0.49, P < 0.001). The scalp-to-cortex distance increased significantly with disease duration (r = 0.56, P < 0.001) and correlated inversely with cortical thickness. The results may reflect the refractory nature of the myoclonus and indicate a possible reactive cortical inhibitory mechanism to the underlying disease process. This is the largest clinical series on Unverricht-Lundborg disease and the first study describing parallel pathophysiological and structural alterations associated with the severity of the symptoms., (© 2013 International Parkinson and Movement Disorder Society.)

Objective: To determine whether a second-scale intertrial interval (ITI) of single-pulse transcranial magnetic stimulation (TMS) affects the measured amplitude of motor-evoked potentials (MEPs) representing individual corticospinal excitability. This was performed to challenge the common assumption of time invariance of such amplitudes., Methods: Navigated TMS was used to map the dominant hemisphere of nine healthy subjects for the cortical representation focus of the contralateral thenar muscle, and resting motor threshold (MT) was determined. Single-trial MEP amplitudes were analyzed from trains of 30 responses induced at an intensity of 120% of the MT, and constant ITIs were investigated at 1, 2, 3, 5, and 10 seconds as well as randomized at ranges of 1-3 seconds, 3-5 seconds, and 5-10 seconds. MEP responses were divided into three blocks of 10 consecutive responses within each stimulation train. Repeated samples ANOVA was used to assess whether the individual characteristic MEP amplitudes were time invariant, i.e., not affected by the different ITIs and stimulus blocks., Results: The individual single-trial MEP amplitudes were affected significantly (P < 0.05) by the ITI (8/8 subjects), block number (5/8 subjects), and ITI by block number interaction (6/8 subjects). One subject was excluded as the sphericity of the variances could not be confirmed. Consequently, the found time variant nature of the individual single-trial MEP amplitudes affected the estimates (means) of individual characteristic MEP amplitudes. This was also observed as a significant block number effect (P < 0.05) across all subjects., Conclusions: The individual characteristic MEP amplitudes are time variant, contrary to the common assumption. Hence, individual characteristic MEP amplitude estimates should be used cautiously, as erroneous conclusions could be made when assuming those as time invariant., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: Transcranial magnetic stimulation (TMS) is used for assessing the excitability of cortical neurons and corticospinal pathways by determining the subject-specific motor threshold (MT). However, the MT is dependent on the TMS instrumentation and exhibits large variation. We hypothesized that between-subject differences in scalp-to-cortex distance could account for the variation in the MT. Computational electric field (EF) estimation could theoretically be applied to reduce the effect of anatomical differences, since it provides a more direct measure of corticospinal excitability., Methods: The resting MT of the thenar musculature of 50 healthy subjects (24 male and 26 female, 22-69 years) was determined bilaterally at the primary motor cortex with MRI-navigated TMS using monophasic and biphasic stimulation. The TMS-induced maximum EF was computed at a depth of 25 mm from the scalp (EF(25 mm)) and at the individual depth of the motor cortex (EF(cortex)) determined from MRI-scans., Results: All excitability parameters (MT, EF(25 mm) and EF(cortex)) correlated significantly with each other (p<0.001). EF(cortex) at MT intensity was 95±20 V/m for biphasic and 120±24 V/m for monophasic stimulation. The MT did not correlate with the anatomical scalp-to-cortex distance, whereas the coil-to-cortex distance was found to correlate positively with the MT and negatively with EF(cortex) (p<0.05)., Discussion: In healthy subjects, the scalp-to-cortex distance is not a significant determinant of the MT, and thus the use of EF(cortex) does not offer substantial advantages. However, it provides a purposeful and promising tool for studying non-motor cortical areas or patient groups with possible disease-related anatomical alterations., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Motor threshold (MT) is a global measure of corticospinal excitability in transcranial magnetic stimulation determined over the primary motor cortex. It is commonly quantified as stimulation intensity (SI(MT)) able to induce a muscle response over certain threshold amplitude after 5/10 consecutive stimuli. SI(MT) is known to be dependent on coil-to-cortex distance (CCD). Hypothetically, the effect of CCD on SI(MT) could be removed by using a computed estimate for the stimulus-induced maximum cortical electric field at MT level (EF(MT)). The CCDs of six volunteers were artificially increased by a maximum of 16.3±3.5mm in 5-7 steps. At each CCD, the MT was estimated for the first dorsal interosseous muscle of the right hand as SI(MT) and EF(MT) as well as threshold curves. We found that SI(MT) correlated with CCD while EF(MT) did not. CCD had a significant effect on the within-subject variation in SI(MT) (F(6,28)=80.16, p<0.0001), but not in EF(MT) (F(6,28)=0.69, p=0.656) (analysis of variance). Furthermore, CCD had a minor, but significant within-subject effect on single-trial motor evoked potentials induced at different stimulation intensities, whereas the obvious major effect was caused by stimulation intensity. In conclusion, EF(MT) can be used as a measure of corticospinal excitability instead of SI(MT) to reduce the effect of within-subject variation in CCD., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Patients with Unverricht-Lundborg disease, also referred to as progressive myoclonus epilepsy type 1, exhibit widespread motor symptoms and signs in addition to epileptic seizures, which suggest abnormal excitability of the primary motor pathways. To explore the plasticity of the sensory-motor cortex, we employed a modern neurophysiological method, the paired associative stimulation protocol, which resembles the concept of long-term potentiation of experimental studies. Seven patients with genetically verified Unverricht-Lundborg disease and 13 healthy control subjects were enrolled in the study to characterize cortical sensory-motor plasticity. In the study protocol, peripheral electric median nerve stimulation preceded navigated transcranial magnetic stimulation targeted to the representation area of thenar musculature on the contralateral primary motor cortex. The protocol consisted of 132 transcranial magnetic stimulation trials at 0.2 Hz, preceded by peripheral sensory stimulation at 25 ms. Motor-evoked potential amplitudes were analyzed at baseline and after the paired associative stimulation protocol at an intensity of 130% of the individual motor threshold. The patients with Unverricht-Lundborg disease exhibited an average decrease of 15% in motor-evoked potential amplitudes 30 minutes after paired associative stimulation, whereas in the control subjects, a significant increase (101%) was observed (P < .05), as expected. The results indicate a lack of normal cortical plasticity in Unverricht-Lundborg disease, which stresses the role of abnormal motor cortical functions or sensorimotor integration as possible pathophysiological contributors to the motor symptoms. The impaired cortical plasticity may be associated with the previously reported structural and physiological abnormalities of the primary motor cortex., (Copyright © 2011 Movement Disorder Society.)

Purpose: Progressive myoclonus epilepsies (PMEs) comprise a heterogeneous group of conditions characterized by an imbalance between excitatory and inhibitory neuronal mechanisms. The aim of this study was to assess the function of the motor cortex in Unverricht-Lundborg disease (ULD), progressive myoclonus epilepsy type 1 (EPM1)., Methods: Genetically verified EPM1 patients (n=24) were studied and compared with healthy subjects (n=24). MRI-navigated transcranial magnetic stimulation (TMS) was used to study the function of the motor cortex. Motor threshold (MT) and cortical silent period (SP) were used as parameters to evaluate cortical excitability. Peripheral muscle responses were recorded at the thenar and hypothenar using on-line electromyography (EMG)., Results: The normal shortening of SP duration with age was not evident in EPM1. Thus, older patients exhibited significantly prolonged SPs in comparison to healthy control subjects (p<0.05). The MTs, measured as both stimulator output percentage and induced electric field strength (EF), were significantly higher in EPM1 patients than in control subjects (p<0.001). The stimulation of the thenar caused a co-activation in the hypothenar with significantly higher amplitudes as compared to controls (p<0.05)., Conclusions: The prolongation of the SPs with age in EPM1 patients suggests a prevailing inhibitory tonus of the primary motor cortex (M1) as possible reactive mechanism to the disease. Antiepileptic drugs may contribute to the increased MT but do not affect the SP. The results and methodology of this study can lead to a better understanding of the pathophysiology and progression of EPM1.

Transcranial magnetic stimulation (TMS) can be used for non-invasive assessment of cortical physiology and descending motor pathways. However, the focus/exact site of cortical activation is considerably widespread in traditional TMS. When combined with MRI-based navigation, it allows specific anatomical areas of the cortex to be stimulated. The peripheral muscle responses to TMS are commonly measured as motor evoked potentials (MEPs). We compared the accuracy of cortical mapping, as well as the congruity of the motor thresholds (MT) and MEPs between navigated and non-navigated TMS procedures. Eight volunteers were studied in two sessions. In each session both hemispheres were stimulated with and without navigation. Non-navigated TMS: Both hemispheres were mapped without navigation to find the representation area of the thenar muscles based on induced MEP amplitudes. MT was then determined at the optimum coil location. Navigated TMS: Individual MR-images were used for the on-line navigation procedure. The cortical representation area of the thenar musculature was mapped at the "hand knob". The optimum stimulus target was used for MT determination. The order of these two procedures was randomized. Following the MT determination, MEPs were recorded from 20 consecutive stimuli. The MTs were similar from session-to-session with no inter-hemispheric differences, and with and without navigation. The stimulus location was more spatially discrete in navigated TMS producing more stable MEPs with significantly higher amplitudes and shorter latencies. In summary, MEPs exhibit significant differences depending on whether navigation is used. However, the MTs are not significantly dependent on the discrete stimulation site.

Navigated transcranial magnetic stimulation (TMS) is a tool for targeted, noninvasive stimulation of cerebral cortex. Transcranial stimuli can depolarize neurons and evoke measurable effects which are unique in two ways: the effects are caused directly and without a consciousness of the subject, and, the responses from peripheral muscles provide a direct measure for the integrity of the whole motor pathway. The clinical relevance of the method has not always been fully exposed because localizing the optimal stimulation site and determining the optimal stimulation strength have been dependent on time-consuming experimentation and skill. Moreover, in many disorders it has been uncertain, whether the lack of motor responses is the result of true pathophysiological changes or merely because of unoptimal stimulation. We characterized the muscle responses from human primary motor cortex system by navigated TMS to provide normative values for the clinically relevant TMS parameters on 65 healthy volunteers aged 22 to 81 years. We delivered focal TMS pulses on the primary motor area (M1) and recorded muscle responses on thenar and anterior tibial muscles. Motor threshold, latencies and amplitudes of motor-evoked potentials, and silent period duration were measured. The correction of the motor-evoked potential latency for subjects' height is provided. In conclusion, we provide a modified baseline of TMS-related parameters for healthy subjects. Earlier such large-scale baseline material has not been available.

The motor threshold (MT) is a fundamental parameter for evaluating cortical excitability in transcranial magnetic stimulation (TMS) despite remarkable variation, both within, and between subjects. We intended to test whether the variation could be reduced by targeting the stimulation on-line and modeling the TMS-induced electric field on individual MR images. Navigated TMS was used to map the primary motor cortex for the representation area of the thenar muscles (abductor pollicis brevis) and to determine the MT. Thirteen healthy subjects participated in the study. To determine the between-subject variation, the MTs of nine subjects were measured with two different stimulators (comparison study). To study the individual variation, the MT measurement was repeated 20 times in four subjects always using the same stimulator (longitudinal study). In the comparison study, the MTs differed significantly between the two stimulators over all subjects (p<0.001), whereas the electric field strengths did not exhibit significant difference between the stimulators. Both, the MTs, and the electric field strengths showed similar variations, which were greater between subjects (comparison study) than within subjects (longitudinal study). In the comparison study, the distance between the locations of the two different coils on the scalp was significantly greater than the distance between the induced electric field maxima in the brain (p<0.001). We conclude that on-line navigation can be used to reduce the variation caused by different stimulator types and individual subject anatomy. In addition, cortical excitability can be evaluated by using computed electric field strength as well as stimulator-dependent MT.