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  • 1.
    Alstermark, Bror
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Pettersson, Lars-Gunnar
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg , Gothenburg.
    Skilled reaching and grasping in the rat: lacking effect of corticospinal lesion2014In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, article id 103Article in journal (Refereed)
    Abstract [en]

    The corticospinal system is a major motor pathway in the control of skilled voluntary movements such as reaching and grasping. It has developed considerably phylogenetically to reach a peak in humans. Because rodents possess advanced forelimb movements that can be used for reaching and grasping food, it is commonly considered that the corticospinal tract (CST) is of major importance for this control also in rodents. A close homology to primate reaching and grasping has been described but with obvious limitations as to independent digit movements, which are lacking in rodents. Nevertheless, it was believed that there are, as in the primate, direct cortico-motoneuronal connections. Later, it was shown that there are no such connections. The fastest excitatory pathway is disynaptic, mediated via cortico-reticulospinal neurons and in the spinal cord the excitation is mainly polysynaptically mediated via segmental interneurons. Earlier behavioral studies have aimed at investigating the role of the CST by using pyramidotomy in the brainstem. However, in addition to interrupting the CST, a pyramidal transection abolishes the input to reticulospinal neurons. It is therefore not possible to conclude if the deficits after pyramidotomy result from interruption of the CST or the input to reticulospinal neurons or both. We have re-investigated the role of the CST by examining the effect of a CST lesion in the C1-C2 spinal segments on the success rate of reaching and grasping. This lesion spares the cortico-reticulospinal pathway. In contrast to investigations using pyramidal transections, the present study did not demonstrate marked deficits in reaching and grasping. We propose that the difference in results can be explained by the intact cortical input to reticulospinal neurons in our study and thus implicate an important role of this pathway in the control of reaching and grasping in the rat.

  • 2. Bartek, Jiri, Jr.
    et al.
    Förander, Petter
    Thurin, Erik
    Wangerid, Theresa
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Regional Cancer Centre Stockholm/Gotland, Stockholm, Sweden.
    Hesselager, Göran
    Jakola, Asgeir Store
    Short-Term Surgical Outcome for Vestibular Schwannoma in Sweden: A Nation-Wide Registry Study2019In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 10, article id 43Article in journal (Refereed)
    Abstract [en]

    Background: Vestibular Schwannoma (VS) is a benign neoplasm arising from the 8th cranial nerve, with surgery one of the treatment modalities. In a nation-wide registry study, we describe the baseline, treatment characteristics, and short-term outcome in patients surgically treated for VS.

    Methods: We performed a nationwide study with data from the Swedish Brain Tumor Registry (SBTR) for all adults diagnosed with VS 2009–2015. Patient symptoms, tumor characteristics, and postoperative complications were analyzed.

    Results: In total 348 patients underwent surgery for VS. Mean age was 50.6 ± 14.5 years and 165 patients (47.4%) were female. The most common symptom was focal neurological deficit (92.0%), with only 25 (7.2%) being asymptomatic prior to surgery, and 217 (63.6%) had no restriction in activity. Following surgery, 100 (28.7%) patients developed new deficit(s). In terms of postoperative complications; 11 (3.2%) had a hematoma, 35 (10.1%) an infection, 10 (2.9%) a venous thromboembolism, and 23 (6.6%) had a reoperation due to complication. There were no deaths within 30-days after surgery. When grouped according to tumor size (< 4 vs. ≥4 cm), those with ≥4 cm tumors were more often males (p = 0.02), had more often ICP related symptoms (p = 0.03) and shorter time from imaging to surgery (p < 0.01). Analysis of the younger (< 65 years) vs. elderly (≥65 years) revealed no difference in outcome except increased 1-year mortality (p = 0.002) in elderly.

    Conclusion: In this nation-wide registry-study, we benchmark the 30-day complication rate after VS surgery as collected by the SBTR. Further, we present the current neurosurgical outcome data from both VS smaller than 40 mm compared to larger tumors, as well as younger vs. elderly VS patients. Since surgical decision making is a careful consideration of short term risk vs. long term benefit, this information can be useful in clinical decision making.

  • 3. Crippa, Sylvain, V
    et al.
    Domellöf, Fatima Pedrosa
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Kawasaki, Aki
    Chromatic pupillometry in children2018In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 9, article id 669Article in journal (Refereed)
    Abstract [en]

    Chromatic pupillometry is a technique that is increasingly used to assess retinal disorders. As age may be one of the various factors which can influence the pupillary light reaction, this study aimed to evaluate the pupil responses to colored light stimuli in the pediatric population. Fifty-three children with normal vision and without any history of ocular disorders were tested with a portable pupillometer. Four test sequences were used: five dim blue (470 nm) stimuli presented in half log steps ranging from -3.15 to -1.15 log cd/m(2) after 3 min of dark adaptation, five red (622 nm) stimuli of -1.15, -0.7, -0.15, 0.3, and 0.85 log cd/m(2) after 1 min light adaptation, one bright blue stimulus of 2.2 log cd/m(2) and one bright red of 2 log cd/m(2). The results were grouped by age: a younger group included 27 children aged from 3 to 10 years old and an older group included 26 from 10 and 1 month to 18 years old. The younger group had a smaller pupil diameter after dark adaptation compared with the older group. A linear regression defining the photopic threshold showed that younger subjects had a higher threshold, e.g., needed a brighter red stimulus to evoke a threshold pupil response comparable that of subjects. Age thus seems to influence outer retinal sensitivity at least as evaluated by the pupillary photopic threshold intensity. The post-illumination pupillary reaction was used as a marker of intrinsic melanopsin activity and did not show any difference between the two age groups.

  • 4. Dahlin, Lars B.
    et al.
    Andersson, Gert
    Backman, Clas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery. Department of Hand Surgery, University Hospital of Northern Sweden, Umeå University, Umeå, Sweden.
    Svensson, Hampus
    Bjorkman, Anders
    Rehabilitation, Using Guided Cerebral plasticity, of a Brachial plexus Injury treated with Intercostal and phrenic Nerve transfers2017In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 8, article id 72Article in journal (Refereed)
    Abstract [en]

    Recovery after surgical reconstruction of a brachial plexus injury using nerve grafting and nerve transfer procedures is a function of peripheral nerve regeneration and cerebral reorganization. A 15-year-old boy, with traumatic avulsion of nerve roots C5-C7 and a non-rupture of C8-T1, was operated 3 weeks after the injury with nerve transfers: ( a) terminal part of the accessory nerve to the suprascapular nerve, (b) the second and third intercostal nerves to the axillary nerve, and (c) the fourth to sixth intercostal nerves to the musculocutaneous nerve. A second operation-free contralateral gracilis muscle transfer directly innervated by the phrenic nerve-was done after 2 years due to insufficient recovery of the biceps muscle function. One year later, electromyography showed activation of the biceps muscle essentially with coughing through the intercostal nerves, and of the transferred gracilis muscle by deep breathing through the phrenic nerve. Voluntary flexion of the elbow elicited clear activity in the biceps/gracilis muscles with decreasing activity in intercostal muscles distal to the transferred intercostal nerves (i.e., corresponding to eighth intercostal), indicating cerebral plasticity, where neural control of elbow flexion is gradually separated from control of breathing. To restore voluntary elbow function after nerve transfers, the rehabilitation of patients operated with intercostal nerve transfers should concentrate on transferring coughing function, while patients with phrenic nerve transfers should focus on transferring deep breathing function.

  • 5.
    Elgh, Eva
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Hu, Xiaolei
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Dynamic Trajectory of Long-Term Cognitive Improvement Up to 10 Years in Young Community-Dwelling Stroke Survivors: A Cohort Study2019In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 10, article id 97Article in journal (Refereed)
    Abstract [en]

    Background and objective: The trajectories of long-term and domain-specific cognitive alterations over a decade after stroke are largely unknown. This study aims to investigate the dynamic alterations of domain-specific cognitive performance among young stroke survivors over 10 years after their first stroke.

    Methods: A prospective cohort study was carried out on 38 young stroke survivors (aged 18-65 at stroke onset) living in the community at 10 years after their first stroke. The cognitive outcomes were assessed repeatedly at 1 week, 7 months, and 10 years after their first stroke on the sub-domains: process speed (Symbol search and Coding from WAIS, TMT-A), visual attention (Bells test), visuospatial function (Block design from WAIS, RCFT), executive function (TMT-B, verbal fluency), verbal function [Letter fluency (FAS) from D-KEFS and CD], working memory (Digit Span from WAIS), immediate memory (RCFT and CD), and delayed memory (RCFT and CD). Global cognition was evaluated with Mini mental state examination at the two later time-points.

    Results: We found a delayed significant improvement of working memory with total recovery 10 years after participants' stroke. Visuospatial function recovered already at 7 months and remained stable at 10-year follow-up. Process speed demonstrated a significant decrease at 10 years compared to 7 months after stroke onset, a decrease which could be compensated by enhancements of other cognitive domains. No further deterioration was found in verbal function, immediate-, and delayed memory, and executive function during 10-year follow-up. Global cognition improved by on average two points between 7 months and 10 years. Education level and fatigue showed low to moderate positive correlations with cognitive improvements.

    Conclusions: The concordance of cognitive improvements between domain-specific and global cognitions strongly suggest that some young stroke survivors do improve their cognitive outcome over a 10-year period following their first stroke. This finding fills a gap of knowledge with respect to the dynamic trajectory of post-stroke cognition, with important implications in clinical practice.

  • 6.
    Johansson, Anna-Maria
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Domellöf, Erik
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Rönnqvist, Louise
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Timing training in three children with diplegi ccerebral palsy: short- and long-term effects on upper-limb movement organization and functioning2014In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, article id 38Article in journal (Refereed)
    Abstract [en]

    Despite the great need of interventions to maintain and improve motor functions in children with diplegic cerebral palsy (DCP), scientific evaluations of existing training methods are rare. This study aimed to explore individual effects of synchronized metronome training (SMT) on motor timing, spatio-temporal movement organization, and subjective experiences of changes in upper-limb functions in three children with DCP. All children participated in an individualized 4-week/12 session SMT training regime. Measurements before training (Pre), after training (Post1), and at 6 months post completed training (Post2) were made by the applied SMT training equipment, optoelectronic registrations of goal-directed upper-limb movements, and a questionnaire assessing subjective experiences of changes in upper-limb functions and usability. In general, the training regime was shown to have little effect on motor timing. However, some positive changes in spatio-temporal movement organization were found. Two children also reported substantial long-lasting positive changes in subjective experiences of hand/arm functionality in terms of increased movement control and reduced muscle tone. For these children, parallel kinematic findings also indicated smoother and faster movement trajectories that remained at Post2. Although highly individualized, the shown improvements in upper-limb kinematics and subjective experiences of improved functionality of the hands/arms for two of the cases warrant further explorations of SMT outcomes in children with DCP.

  • 7. Nordström, Carl-Henrik
    et al.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Olivecrona, Magnus
    Aspects on the Physiological and Biochemical Foundations of Neurocritical Care2017In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 8, article id 274Article, review/survey (Refereed)
    Abstract [en]

    Neurocritical care (NCC) is a branch of intensive care medicine characterized by specific physiological and biochemical monitoring techniques necessary for identifying cerebral adverse events and for evaluating specific therapies. Information is primarily obtained from physiological variables related to intracranial pressure (ICP) and cerebral blood flow (CBF) and from physiological and biochemical variables related to cerebral energy metabolism. Non-surgical therapies developed for treating increased ICP are based on knowledge regarding transport of water across the intact and injured blood-brain barrier (BBB) and the regulation of CBF. Brain volume is strictly controlled as the BBB permeability to crystalloids is very low restricting net transport of water across the capillary wall. Cerebral pressure autoregulation prevents changes in intracranial blood volume and intracapillary hydrostatic pressure at variations in arterial blood pressure. Information regarding cerebral oxidative metabolism is obtained from measurements of brain tissue oxygen tension (PbtO2) and biochemical data obtained from intracerebral microdialysis. As interstitial lactate/pyruvate (LP) ratio instantaneously reflects shifts in intracellular cytoplasmatic redox state, it is an important indicator of compromised cerebral oxidative metabolism. The combined information obtained from PbtO2, LP ratio, and the pattern of biochemical variables reveals whether impaired oxidative metabolism is due to insufficient perfusion (ischemia) or mitochondrial dysfunction. Intracerebral microdialysis and PbtO2 give information from a very small volume of tissue. Accordingly, clinical interpretation of the data must be based on information of the probe location in relation to focal brain damage. Attempts to evaluate global cerebral energy state from microdialysis of intraventricular fluid and from the LP ratio of the draining venous blood have recently been presented. To be of clinical relevance, the information from all monitoring techniques should be presented bedside online. Accordingly, in the future, the chemical variables obtained from microdialysis will probably be analyzed by biochemical sensors.

  • 8. Penner, Iris-Katharina
    et al.
    Sivertsdotter, Eva Catharina
    Celius, Elisabeth G.
    Fuchs, Siegrid
    Schreiber, Karen
    Berko, Sara
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Improvement in fatigue during natalizumab treatment is linked to improvement in depression and day-time sleepiness2015In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 6, article id UNSP 18Article in journal (Refereed)
    Abstract [en]

    Background: Fatigue is a frequent symptom in multiple sclerosis (MS) and often interrelated with depression and sleep disorders making symptomatic treatment decisions difficult. In the single-arm, observational phase IVTYNERGY study, relapsing remitting MS patients showed a clinically meaningful decrease in fatigue over 1 year of treatment with natalizumab. Objective: To evaluate whether fatigue improvement might be directly linked to improved depression and day-time sleepiness. Methods: Patients were assessed regarding fatigue, depression, and day-time sleepiness. The relation between changes of the two latter symptoms and changes in fatigue was analyzed. Results: After 1 year of natalizumab treatment, the majority of patients (>92%) remained stable or improved in total, motor, and cognitive fatigue. Proportion of patients without depression increased by 17% while proportions of mildly depressed patients or patients with potential major depression decreased by 5 and 12%, respectively. Proportion of patients classified as not being sleepy increased by 13% while proportions of sleepy and very sleepy patients decreased by 11 and 2%, respectively. Most importantly, improved depression and sleepiness were significantly related to improved fatigue. Conclusion: Our findings highlight the importance of patient-reported outcomes in identifying potential benefits of drug treatment beyond its well-established effects on disease activity and disability progression.

  • 9.
    Pinto, Susana
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Rehabilitation Medicine. Faculdade de Medicina, Instituto de Fisiologia e Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon, Portugal; Department of Neurosciences and Mental Health, Hospital de Santa Maria-Centro Hospitalar Lisboa Norte, Lisbon, Portugal.
    de Carvalho, Mamede
    SVC Is a Marker of Respiratory Decline Function, Similar to FVC , in Patients With ALS2019In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 10, article id 109Article in journal (Refereed)
    Abstract [en]

    Introduction: Respiratory function is a critical predictor of survival in amyotrophic lateral sclerosis (ALS). We aimed to determine if slow vital capacity (SVC) is a predictor of functional loss in ALS as compared to forced vital capacity (FVC). Methods: Consecutive ALS patients in whom respiratory tests were performed at baseline and 6 months later were included. All patients were evaluated with revised ALS functional rating scale (ALSFRS-R) and the respiratory tests, SVC, and FVC. Significant independent variables of functional decay were assessed by univariate Kaplan-Meier log-rank test and multivariate Cox proportional hazards model. A monthly decay not exceeding 0.92 in ALSFRS was considered as the time event. Results: We included 232 patients (134 men; mean onset-age 59.1 +/- 11.23 years; mean disease duration from first symptoms to first visit: 14.5 +/- 12.9 months; 166 spinal and 66 bulbar onset). All variables studied declined significantly between the two evaluations (p < 0.001). FVC and SVC were strongly correlated at study entry (r2 = 0.98, p < 0.001) and FVC and SVC decays between first evaluation and 6 months after were the only significant prognostic variables of functional decay (p < 0.001). Conclusion: FVC and SVC decay are inter-changeable in predicting functional decay in ALS. Pharmacological interventions reducing the decline rate of FVC and SVC can have a positive impact on the global functional impairment, with relevant implications for clinical trials' design and interpretation.

  • 10.
    Sandvig, Axel
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience. Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Department of Neurology, St. Olav’s Hospital, Trondheim University Hospital, Trondheim, Norway.
    Sandvig, Ioanna
    Connectomics of Morphogenetically Engineered Neurons as a Predictor of Functional Integration in the Ischemic Brain2019In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 10, article id 630Article, review/survey (Refereed)
    Abstract [en]

    Recent advances in cell reprogramming technologies enable the in vitro generation of theoretically unlimited numbers of cells, including cells of neural lineage and specific neuronal subtypes from human, including patient-specific, somatic cells. Similarly, as demonstrated in recent animal studies, by applying morphogenetic neuroengineering principles in situ, it is possible to reprogram resident brain cells to the desired phenotype. These developments open new exciting possibilities for cell replacement therapy in stroke, albeit not without caveats. Main challenges include the successful integration of engineered cells in the ischemic brain to promote functional restoration as well as the fact that the underlying mechanisms of action are not fully understood. In this review, we aim to provide new insights to the above in the context of connectomics of morphogenetically engineered neural networks. Specifically, we discuss the relevance of combining advanced interdisciplinary approaches to: validate the functionality of engineered neurons by studying their self-organizing behavior into neural networks as well as responses to stroke-related pathology in vitro; derive structural and functional connectomes from these networks in healthy and perturbed conditions; and identify and extract key elements regulating neural network dynamics, which might predict the behavior of grafted engineered neurons post-transplantation in the stroke-injured brain.

  • 11. Smits, Anja
    et al.
    Zetterling, Maria
    Lundin, Margareta
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Fahistrom, Markus
    Grabowska, Anna
    Larsson, Eina-Marie
    Berntsson, Shale Ghaderi
    Neurological impairment linked with cortico-subcortical infiltration of diffuse low-grade gliomas at initial diagnosis supports early brain plasticity2015In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 6, article id UNSP 137Article in journal (Refereed)
    Abstract [en]

    Diffuse low-grade gliomas (DLGG) are slow-growing brain tumors that in spite of an indolent behavior at onset show a continuous expansion over time and inevitably transform into malignant gliomas. Extensive tumor resections may be performed with preservation of neurological function due to neuroplasticity that is induced by the slow tumor growth. However, DLGG prefer to migrate along subcortical pathways, and white matter plasticity is considerably more limited than gray matter plasticity. Whether signs of functional decompensating white matter that may be found as early as at disease presentation has not been systematically studied. Here, we examined 52 patients who presented with a DLGG at the time of radiological diagnosis. We found a significant correlation between neurological impairment and eloquent cortico-subcortical tumor localization, but not between neurological function and tumor volume. These results suggest that even small tumors invading white matter pathways may lack compensatory mechanisms for functional reorganization already at disease presentation.

  • 12. Zimmerman, Malin
    et al.
    Pourhamidi, Kaveh
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Dahlin, Lars B.
    Autonomic Neuropathy: a Prospective Cohort Study of Symptoms and E/I Ratio in Normal Glucose Tolerance, Impaired Glucose Tolerance, and Type 2 Diabetes2018In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 9, article id 154Article in journal (Refereed)
    Abstract [en]

    Background: Autonomic neuropathy in diabetes, in addition to causing a range of symptoms originating from the autonomic nervous system, may increase cardiovascular morbidity. Our aim was to study the progression of autonomic neuropathy, based on symptom score and evaluation of an autonomic test, in persons with normal and impaired glucose tolerance and in patients with type 2 diabetes (T2D).

    Methods: Participants were recruited in 2003/2004 with a follow-up in 2014. The participants' glucose tolerance was categorized using oral glucose tolerance tests. Symptoms were evaluated using an autonomic symptom score (ASS), ECG was used to test cardiac autonomic function based on the expiration/inspiration ratio (E/I ratio), and blood samples were taken on both occasions.

    Results: ASSs were higher at follow-up in the T2D patients than in the normal glucose tolerance group (mean 1.21 +/- 1.30 vs. 0.79 +/- 0.7; p < 0.05). E/I ratio did not deteriorate more than could be expected as an aging effect in well-controlled T2D. No relationship was found between E/I ratio and HbA1c or ASS.

    Conclusion: The presence of autonomic symptoms increased over time in T2D patients, but the symptoms did not correlate with the Ell ratio in this metabolically well-controlled cohort. ASSs can be a useful clinical tool when assessing the progression of autonomic dysfunction in patients with abnormal glucose metabolism.

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