Publications by authors named "Mans Magnusson"

107 Publications

Short-Latency Covert Saccades - The Explanation for Good Dynamic Visual Performance After Unilateral Vestibular Loss?

Front Neurol 2021 31;12:695064. Epub 2021 Aug 31.

Department of Clinical Sciences, Otorhinolaryngology Head and Neck Surgery, Skåne University Hospital, Lund University, Lund, Sweden.

Functional head impulse test (fHIT) tests the ability of the vestibulo-ocular reflex (VOR) to allow visual perception during head movements. Our previous study showed that active head movements to the side with a vestibular lesion generated a dynamic visual performance that were as good as during movements to the intact side. To examine the differences in eye position during the head impulse test when performed with active and passive head movements, in order to better understand the role of the different saccade properties in improving visual performance. We recruited 8 subjects with complete unilateral vestibular loss (4 men and 4 women, mean age 47 years) and tested them with video Head Impulse Test (vHIT) and Functional Head Impulse Test (fHIT) during passive and active movements while looking at a target. We assessed the mean absolute position error of the eye during different time frames of the head movement, the peak latency and the peak velocity of the first saccade, as well as the visual performance during the head movement. Active head impulses to the lesioned side generated dynamic visual performances that were as good as when testing the intact side. Active head impulses resulted in smaller position errors during the visual perception task ( = 0.006) compared to passive head-impulses and the position error during the visual perception time frame correlated with shorter latencies of the first saccade ( < 0.001). Actively generated head impulses toward the side with a complete vestibular loss resulted in a position error within or close to the margin necessary to obtain visual perception for a brief period of time in patients with chronic unilateral vestibular loss. This seems to be attributed to the appearance of short-latency covert saccades, which position the eyes in a more favorable position during head movements.
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http://dx.doi.org/10.3389/fneur.2021.695064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439257PMC
August 2021

Robotized Testing of Camera Positions to Determine Ideal Configuration for Stereo 3D Visualization of Open-Heart Surgery.

J Vis Exp 2021 08 12(174). Epub 2021 Aug 12.

Cardiac Surgery Unit, Children's Heart Centre, Skåne University Hospital.

Stereo 3D video from surgical procedures can be highly valuable for medical education and improve clinical communication. But access to the operating room and the surgical field is restricted. It is a sterile environment, and the physical space is crowded with surgical staff and technical equipment. In this setting, unobscured capture and realistic reproduction of the surgical procedures are difficult. This paper presents a method for rapid and reliable data collection of stereoscopic 3D videos at different camera baseline distances and distances of convergence. To collect test data with minimum interference during surgery, with high precision and repeatability, the cameras were attached to each hand of a dual-arm robot. The robot was ceiling-mounted in the operating room. It was programmed to perform a timed sequence of synchronized camera movements stepping through a range of test positions with baseline distance between 50-240 mm at incremental steps of 10 mm, and at two convergence distances of 1100 mm and 1400 mm. Surgery was paused to allow 40 consecutive 5-s video samples. A total of 10 surgical scenarios were recorded.
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http://dx.doi.org/10.3791/62786DOI Listing
August 2021

vHIT Testing of Vertical Semicircular Canals With Goggles Yield Different Results Depending on Which Canal Plane Being Tested.

Front Neurol 2021 27;12:692196. Epub 2021 Jul 27.

Department of Otorhinolaryngology, Head and Neck Surgery, Clinical Sciences, Lund Skåne University Hospital Lund, Lund, Sweden.

The use of goggles to assess vertical semicircular canal function has become a standard method in vestibular testing, both in clinic and in research, but there are different methods and apparatus in use. The aim of this study was to determine what the cause of the systematic differences is between gain values in testing of the vertical semicircular canals with two different video head impulse test (vHIT) equipment in subjects with normal vestibular function. Retrospective analysis of gain values on patients with clinically deemed normal vestibular function (absence of a corrective eye saccade), tested with either Interacoustics or Otometrics system. Prospective testing of subjects with normal vestibular function with the camera records the eye movements of both eyes. Finally, 3D sensors were placed on different positions on the goggles measuring the actual vertical movement in the different semicircular planes. In the clinical cohorts, the gain depended on which side and semicircular canal was tested ( < 0.001). In the prospective design, the combination between the stimulated side, semicircular canal, and position of the recording device (right/left eye) highly influenced the derived gain ( < 0.001). The different parts of the goggles also moved differently in a vertical direction during vertical semicircular canal testing. The gain values when testing the function of the vertical semicircular canals seem to depend upon which eye is recorded and which semicircular plane is tested and suggests caution when interpreting and comparing results when different systems are used both clinically as well as in research. The results also imply that further research and development are needed to obtain accurate vertical semicircular canal testing, in regard to both methodology and equipment design.
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http://dx.doi.org/10.3389/fneur.2021.692196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353365PMC
July 2021

Cortical Activity During an Attack of Ménière's Disease-A Case Report.

Front Neurol 2021 22;12:669390. Epub 2021 Jul 22.

Department of Oto-Rhino-Laryngology, Lund University Hospital, Lund, Sweden.

Ménière's disease (MD) is a chronic peripheral vestibular disorder with recurrent episodes of vertigo accompanied by fluctuating hearing loss, tinnitus and aural fullness in the affected ear. There are several unanswered fundamental questions regarding MD, one of these being cortical activity during a MD attack. However, it is not possible to plan an investigation in an episodic disease as MD. To visualize cortical activity during an attack of MD. F-FDG PET scans were used to visualize cortical activity in a 62 years old male suffering from definite MD. Two F-FDG PET scans were performed. One to show activity during the attack and one to show normal baseline brain activity 7 days after the attack. A number of low-magnitude fluctuations in the F-FDG FDG uptake were found in F-FDG PET examination following the MD attack compared to the patient's own baseline F-FDG FDG scan. Across both hemispheres no significant changes were seen. However, reduced activity was observed in most of the orbitofrontal, frontal cortices as well as Heschl's gyrus and insula. This is the first neuroimaging showing alteration of brain activity during an attack in a patient with MD. No strong focal alterations was seen. It is noteworthy that the decreased activity observed was in the insula and Heschl's gyrus that seems to be core areas for processing information from the labyrinth. It is also of interest that decreased activity rather than hyperactivity was observed.
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http://dx.doi.org/10.3389/fneur.2021.669390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339298PMC
July 2021

Gait Flexibility among Older Persons Significantly More Impaired in Fallers Than Non-Fallers-A Longitudinal Study.

Int J Environ Res Public Health 2021 07 2;18(13). Epub 2021 Jul 2.

Department of Clinical Sciences in Lund/ENT, Lund University, 22185 Lund, Sweden.

Gait disorders are a relevant factor for falls and possible to measure with wearable devices. If a wearable sensor can detect differences in gait parameters between fallers and non-fallers has not yet been studied. The aim of this study was to measure and compare gait parameters, vestibular function, and balance performance between fallers and non-fallers among a group of older persons. Participants were senior members ( = 101) of a Swedish non-profit gymnastic association. Gait parameters were obtained using an inertial measurement unit (IMU) that the participants wore on the leg while walking an obstacle course and on an even surface. Vestibular function was assessed by the Head-shake test, the Head impulse test, and the Dix-Hallpike maneuver. Balance was assessed by the Timed Up and Go, the Timed Up and Go manual, and the Timed Up and Go cognitive tests. Falls during the 12-month follow-up period were monitored using fall diaries. Forty-two persons (41%) had fallen during the 12-month follow-up. Fallers had more limited ability to vary their gait (gait flexibility) than non-fallers ( < 0.001). No other differences between fallers and non-fallers were found. The use of gait flexibility, captured by an IMU, seems better for identifying future fallers among healthy older persons than Timed Up and Go or Timed Up and Go combined with a cognitive or manual task.
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http://dx.doi.org/10.3390/ijerph18137074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297078PMC
July 2021

High diagnostic yield in skeletal ciliopathies using massively parallel genome sequencing, structural variant screening and RNA analyses.

J Hum Genet 2021 Oct 20;66(10):995-1008. Epub 2021 Apr 20.

Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, and Department of Clinical Genetics, Karolinska University Laboratory, Karolinska University Hospital, Stockholm, Sweden.

Skeletal ciliopathies are a heterogenous group of disorders with overlapping clinical and radiographic features including bone dysplasia and internal abnormalities. To date, pathogenic variants in at least 30 genes, coding for different structural cilia proteins, are reported to cause skeletal ciliopathies. Here, we summarize genetic and phenotypic features of 34 affected individuals from 29 families with skeletal ciliopathies. Molecular diagnostic testing was performed using massively parallel sequencing (MPS) in combination with copy number variant (CNV) analyses and in silico filtering for variants in known skeletal ciliopathy genes. We identified biallelic disease-causing variants in seven genes: DYNC2H1, KIAA0753, WDR19, C2CD3, TTC21B, EVC, and EVC2. Four variants located in non-canonical splice sites of DYNC2H1, EVC, and KIAA0753 led to aberrant splicing that was shown by sequencing of cDNA. Furthermore, CNV analyses showed an intragenic deletion of DYNC2H1 in one individual and a 6.7 Mb de novo deletion on chromosome 1q24q25 in another. In five unsolved cases, MPS was performed in family setting. In one proband we identified a de novo variant in PRKACA and in another we found a homozygous intragenic deletion of IFT74, removing the first coding exon and leading to expression of a shorter message predicted to result in loss of 40 amino acids at the N-terminus. These findings establish IFT74 as a new skeletal ciliopathy gene. In conclusion, combined single nucleotide variant, CNV and cDNA analyses lead to a high yield of genetic diagnoses (90%) in a cohort of patients with skeletal ciliopathies.
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http://dx.doi.org/10.1038/s10038-021-00925-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472897PMC
October 2021

Spectral analysis of body movement during deep brain stimulation in Parkinson's disease.

Gait Posture 2021 05 18;86:217-225. Epub 2021 Mar 18.

Department of Clinical Sciences, Lund University, S-221 85 Lund, Sweden. Electronic address:

Background: The characteristics of Parkinson's disease (PD) include postural instability and resting tremor. However, reductions of tremor amplitude do not always improve postural stability.

Research Question: What is the effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on spectral analysis of body movement in patients with PD when tested without anti-PD medication? The effect of visual cues was also studied.

Methods: Ten patients with PD (mean age 64.3 years, range 59-69 years) and 17 control participants (mean age 71.2 years, range 65-79 years) were recruited. Spectral power following a period of quiet stance (35 s) was analysed in three different spectral power bands (0-4 Hz, 4-7 Hz and 7-25 Hz). Motion markers were secured to the head, shoulder, hip, and knee, which recorded movements in two directions, the anteroposterior and lateral.

Results: DBS STN significantly changed the spectral distribution pattern across the body in the anteroposterior (p = 0.029) and lateral directions (p ≤ 0.003). DBS predominantly reduced spectral power at the head (p ≤ 0.037) and shoulder (p ≤ 0.031) in the lateral direction. The spectral power of the lower and upper body in patients with PD, with DBS ON, were more similar to the control group, than to DBS OFF. Visual cues mainly reduced spectral power in the anteroposterior direction at the shoulder (p ≤ 0.041) in controls and in patients with PD with DBS ON.

Significance: There is an altered postural strategy in patients with PD with DBS ON as shown by an altered spectral power distribution pattern across body segments and a reduction of spectral power in the lateral direction at the head and shoulder. A reduction of spectral power in controls and in patients with PD with DBS ON suggests that visual cues are able to reduce spectral power to some extent, but not with DBS OFF where postural sway and power are larger.
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http://dx.doi.org/10.1016/j.gaitpost.2021.03.023DOI Listing
May 2021

Integration of whole genome sequencing into a healthcare setting: high diagnostic rates across multiple clinical entities in 3219 rare disease patients.

Genome Med 2021 03 17;13(1):40. Epub 2021 Mar 17.

Science for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institutet of Technology, Stockholm, Sweden.

Background: We report the findings from 4437 individuals (3219 patients and 1218 relatives) who have been analyzed by whole genome sequencing (WGS) at the Genomic Medicine Center Karolinska-Rare Diseases (GMCK-RD) since mid-2015. GMCK-RD represents a long-term collaborative initiative between Karolinska University Hospital and Science for Life Laboratory to establish advanced, genomics-based diagnostics in the Stockholm healthcare setting.

Methods: Our analysis covers detection and interpretation of SNVs, INDELs, uniparental disomy, CNVs, balanced structural variants, and short tandem repeat expansions. Visualization of results for clinical interpretation is carried out in Scout-a custom-developed decision support system. Results from both singleton (84%) and trio/family (16%) analyses are reported. Variant interpretation is done by 15 expert teams at the hospital involving staff from three clinics. For patients with complex phenotypes, data is shared between the teams.

Results: Overall, 40% of the patients received a molecular diagnosis ranging from 19 to 54% for specific disease groups. There was heterogeneity regarding causative genes (n = 754) with some of the most common ones being COL2A1 (n = 12; skeletal dysplasia), SCN1A (n = 8; epilepsy), and TNFRSF13B (n = 4; inborn errors of immunity). Some causative variants were recurrent, including previously known founder mutations, some novel mutations, and recurrent de novo mutations. Overall, GMCK-RD has resulted in a large number of patients receiving specific molecular diagnoses. Furthermore, negative cases have been included in research studies that have resulted in the discovery of 17 published, novel disease-causing genes. To facilitate the discovery of new disease genes, GMCK-RD has joined international data sharing initiatives, including ClinVar, UDNI, Beacon, and MatchMaker Exchange.

Conclusions: Clinical WGS at GMCK-RD has provided molecular diagnoses to over 1200 individuals with a broad range of rare diseases. Consolidation and spread of this clinical-academic partnership will enable large-scale national collaboration.
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http://dx.doi.org/10.1186/s13073-021-00855-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968334PMC
March 2021

Motion sickness diagnostic criteria: Consensus Document of the Classification Committee of the Bárány Society.

J Vestib Res 2021 ;31(5):327-344

Naval Submarine Medical Research Laboratory, Naval Submarine Base New London, Groton, CT, USA.

We present diagnostic criteria for motion sickness, visually induced motion sickness (VIMS), motion sickness disorder (MSD), and VIMS disorder (VIMSD) to be included in the International Classification of Vestibular Disorders. Motion sickness and VIMS are normal physiological responses that can be elicited in almost all people, but susceptibility and severity can be high enough for the response to be considered a disorder in some cases. This report provides guidelines for evaluating signs and symptoms caused by physical motion or visual motion and for diagnosing an individual as having a response that is severe enough to constitute a disorder.   The diagnostic criteria for motion sickness and VIMS include adverse reactions elicited during exposure to physical motion or visual motion leading to observable signs or symptoms of greater than minimal severity in the following domains: nausea and/or gastrointestinal disturbance, thermoregulatory disruption, alterations in arousal, dizziness and/or vertigo, headache and/or ocular strain. These signs and/or symptoms occur during the motion exposure, build as the exposure is prolonged, and eventually stop after the motion ends. Motion sickness disorder and VIMSD are diagnosed when recurrent episodes of motion sickness or VIMS are reliably triggered by the same or similar stimuli, severity does not significantly decrease after repeated exposure, and signs/symptoms lead to activity modification, avoidance behavior, or aversive emotional responses.   Motion sickness/MSD and VIMS/VIMSD can occur separately or together. Severity of symptoms in reaction to physical motion or visual motion stimuli varies widely and can change within an individual due to aging, adaptation, and comorbid disorders. We discuss the main methods for measuring motion sickness symptoms, the situations conducive to motion sickness and VIMS, and the individual traits associated with increased susceptibility. These additional considerations will improve diagnosis by fostering accurate measurement and understanding of the situational and personal factors associated with MSD and VIMSD.
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http://dx.doi.org/10.3233/VES-200005DOI Listing
January 2021

Co-morbidities to Vestibular Impairments-Some Concomitant Disorders in Young and Older Adults.

Front Neurol 2020 27;11:609928. Epub 2021 Jan 27.

Department of Clinical Sciences, Section of Otorhinolaryngology, Lund University, Lund, Sweden.

Dizziness and pain are common complaints that often appear concomitantly, with or without a causal relationship. However, these symptoms might maintain and exacerbate each other and other co-morbidities. Therefore, adequate rehabilitation may have to include an expanded focus on other deficits and preconditions, especially in older adults and in patients. To understand how frequently vestibular dysfunction coincided with medical conditions and aging, we studied two categories: Study 1: patients referred to a vestibular unit and Study 2: senior members in a fitness association. Study 1: 49 patients [34 females/15 males; mean age 52 years (SEM 2.0)] seeking health care for balance disorders and vestibular deficits were asked in questionnaires about their perception of dizziness and pain, and emotional and functional strains. Study 2: 101 senior members in a fitness association [91 females/10 males; mean age 75 years (SEM 0.6)], were assessed for vestibular and balance deficits and for any co-morbidities. The participants were monitored for falls for 12 months after the initial assessments. Study 1: Co-morbidity often existed between dizziness and pain (65%). The patients reported high emotional and functional strain related to their dizziness and pain. Patients older than 60 years reported longer durations of pain ( ≤ 0.028) but less emotional strain ( = 0.036), compared to younger patients. Study 2: 84% of the participants had a vestibular impairment, often without noticing any symptoms. Furthermore, 40% reported cardiovascular illnesses, 12% musculoskeletal disorders, and 63% reported other medical conditions. Forty-two percent experienced falls within 1 year after the initial assessments (thereof 42% in the group with vestibular deficits and 38% in the group without vestibular deficits). To enhance and preserve postural control, both in patients with vestibular deficits and in older adults, we suggest an expanded clinical perspective. Hence, we recommend detailed examinations of the vestibular system but simultaneously probing for possible co-morbidities. Since aging often entails deterioration of multimodal processes related to maintained mobility and postural stability, our results add focus on the importance of addressing balance disorders together with additional medical conditions.
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http://dx.doi.org/10.3389/fneur.2020.609928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873354PMC
January 2021

Mal de débarquement syndrome diagnostic criteria: Consensus document of the Classification Committee of the Bárány Society.

J Vestib Res 2020 ;30(5):285-293

Departments of Psychiatry and Psychology and Otorhinolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, MN., USA.

We present diagnostic criteria for mal de débarquement syndrome (MdDS) for inclusion into the International Classification of Vestibular Disorders. The criteria include the following: 1] Non-spinning vertigo characterized by an oscillatory perception ('rocking,' 'bobbing,' or 'swaying') present continuously or for most of the day; 2] Onset occurs within 48 hours after the end of exposure to passive motion, 3] Symptoms temporarily reduce with exposure to passive motion (e.g. driving), and 4] Symptoms persist for >48 hours. MdDS may be designated as "in evolution," if symptoms are ongoing but the observation period has been less than 1 month; "transient," if symptoms resolve at or before 1 month and the observation period extends at least to the resolution point; or "persistent" if symptoms last for more than 1 month. Individuals with MdDS may develop co-existing symptoms of spatial disorientation, visual motion intolerance, fatigue, and exacerbation of headaches or anxiety. Features that distinguish MdDS from vestibular migraine, motion sickness, and persistent postural perceptual dizziness (PPPD) are reviewed. Motion-moderated oscillatory vertigo can also occur without a motion trigger, typically following another vestibular disorder, a medical illness, heightened psychological stress, or metabolic disturbance. Terminology for this non-motion triggered presentation has been varied as it has features of both MdDS and PPPD. Further research is needed into its phenomenological and biological relationship to MdDS, PPPD, and other vestibular disorders.
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http://dx.doi.org/10.3233/VES-200714DOI Listing
October 2021

mutations cause NKCC1 deficiency with encephalopathy and impaired secretory epithelia.

Neurol Genet 2020 Aug 2;6(4):e478. Epub 2020 Jul 2.

Department of Women's and Children's Health (T.S.), Department of Molecular Medicine and Surgery (M.M., N.L., H.S., A. Wedell), Science for Life Laboratory (M.M., H.S., A. Wedell), Department of Medical Biochemistry and Biophysics (A. Wredenberg), and Department of Clinical Neuroscience (D.M.M.), Karolinska Institutet; and Department of Pediatric Neurology (T.S.), Centre for Inherited Metabolic Diseases (N.L., A. Wredenberg, H.S., A. Wedell), and Department of Neuroradiology (D.M.M.), Karolinska University Hospital, Stockholm, Sweden.

Objective: To describe the phenotype in 2 sisters with a rare constellation of neurologic symptoms and secretory impairments and to identify the etiology by the use of whole-genome sequencing (WGS).

Methods: After an extensive workup failed to reveal the cause of disease, in a girl with a previously not reported phenotype, WGS of the proband, her diseased older sister, an older healthy brother, and their parents was performed, and potentially pathogenic variants were analyzed.

Results: The proband and her older sister both presented with neonatal parotitis, apneas, disappearance of the Moro reflex, and hypotonia. The proband survived. Her brain MRI showed white matter and basal ganglia abnormalities, and CSF damage biomarkers were increased. At age 8 years, she exhibits a constellation of symptoms including severe neurodevelopmental disorder, hearing impairment, gastrointestinal problems, and a striking lack of tear fluid, saliva, and sweat. Her respiratory mucosa is dry with potentially life-threatening mucus plugging. Through WGS, 2 loss-of-function variants in were identified that follow an autosomal recessive inheritance pattern.

Conclusions: Taken together with a single previously reported case and the close resemblance to the phenotypes of corresponding mouse models, our study firmly establishes biallelic variants in as causing human disease and adds data regarding the neurologic phenotype.
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http://dx.doi.org/10.1212/NXG.0000000000000478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357422PMC
August 2020

Effects of Deep Brain Stimulation on Postural Control in Parkinson's Disease.

Comput Biol Med 2020 07 29;122:103828. Epub 2020 May 29.

Department of Clinical Sciences, Lund University, S-221 85, Lund, Sweden.

The standard approach to the evaluation of tremor in medical practice is subjective scoring. The objective of this study was to show that signal processing of physiological data, that are known to be altered by tremor in Parkinson's disease (PD), can quantify the postural dynamics and the effects of DBS. We measured postural control and its capacity to adapt to balance perturbations with a force platform and perturbed balance by altering visual feedback and using pseudo-random binary sequence perturbations (PRBS) of different durations. Our signal processing involved converting the postural control data into spectral power with Fast-Fourier Transformation across a wide bandwidth and then subdividing this into three bands (0-4 Hz, 4-7 Hz and 7-25 Hz). We quantified the amount of power in each bandwidth. From 25 eligible participants, 10 PD participants (9 males, mean age 63.8 years) fulfilled the inclusion criteria; idiopathic PD responsive to l-Dopa; >1 year use of bilateral STN stimulation. Seventeen controls (9 males, mean age 71.2 years) were studied for comparison. Participants with PD were assessed after overnight withdrawal of anti-PD medications. Postural control was measured with a force platform during quiet stance (35 s) and during PRBS calf muscle vibration that perturbed stance (200 s). Tests were performed with eyes open and eyes closed and with DBS ON and DBS OFF. The balance perturbation period was divided into five sequential 35-s periods to assess the subject's ability to address postural imbalance using adaptation. The signal processing analyses revealed that DBS did not significantly change the dynamics of postural control in the 0-4 Hz spectral power but the device reduced the use of spectral power >4 Hz; a finding that was present in both anteroposterior and lateral directions, during vibration, and more so in eyes open tests. Visual feedback, which usually improves postural stability, was less effective in participants with PD with DBS OFF across all postural sway frequencies during quiet stance and during balance perturbations. The expected adaptation of postural control was found in healthy participants between the first and last balance perturbation period. However, adaptation was almost abolished across all spectral frequencies in both the anteroposterior and lateral directions, with both eyes open and eyes closed and DBS ON and OFF in participants with PD. To conclude, this study revealed that DBS altered the spectral frequency dynamics of postural control in participants through a reduction of the power used >4 Hz. Moreover, DBS tended to increase the stabilizing effect of vision across all spectral bands. However, the signal processing analyses also revealed that DBS was not able to restore adaptive motor control abilities in PD.
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http://dx.doi.org/10.1016/j.compbiomed.2020.103828DOI Listing
July 2020

Loqusdb: added value of an observations database of local genomic variation.

BMC Bioinformatics 2020 Jul 1;21(1):273. Epub 2020 Jul 1.

Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.

Background: Exome and genome sequencing is becoming the method of choice for rare disease diagnostics. One of the key challenges remaining is distinguishing the disease causing variants from the benign background variation. After analysis and annotation of the sequencing data there are typically thousands of candidate variants requiring further investigation. One of the most effective and least biased ways to reduce this number is to assess the rarity of a variant in any population. Currently, there are a number of reliable sources of information for major population frequencies when considering single nucleotide variants (SNVs) and small insertion and deletions (INDELs), with gnomAD as the most prominent public resource available. However, local variation or frequencies in sub-populations may be underrepresented in these public resources. In contrast, for structural variation (SV), the background frequency in the general population is more or less unknown mostly due to challenges in calling SVs in a consistent way. Keeping track of local variation is one way to overcome these problems and significantly reduce the number of potential disease causing variants retained for manual inspection, both for SNVs and SVs.

Results: Here, we present loqusdb, a tool to solve the challenge of keeping track of any type of variant observations from genome sequencing data. Loqusdb was designed to handle a large flow of samples and unlike other solutions, samples can be added continuously to the database without rebuilding it, facilitating improvements and additions. We assessed the added value of a local observations database using 98 samples annotated with information from a background of 888 unrelated individuals.

Conclusions: We show both how powerful SV analysis can be when filtering for population frequencies and how the number of apparently rare SNVs/INDELs can be reduced by adding local population information even after annotating the data with other large frequency databases, such as gnomAD. In conclusion, we show that a local frequency database is an attractive, and a necessary addition to the publicly available databases that facilitate the analysis of exome and genome data in a clinical setting.
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http://dx.doi.org/10.1186/s12859-020-03609-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329469PMC
July 2020

Exploring the effects of deep brain stimulation and vision on tremor in Parkinson's disease - benefits from objective methods.

J Neuroeng Rehabil 2020 04 25;17(1):56. Epub 2020 Apr 25.

Division of Brain Sciences, Imperial College London, London, W6 8RF, UK.

Background: Tremor is a cardinal symptom of Parkinson's disease (PD) that may cause severe disability. As such, objective methods to determine the exact characteristics of the tremor may improve the evaluation of therapy. This methodology study aims to validate the utility of two objective technical methods of recording Parkinsonian tremor and evaluate their ability to determine the effects of Deep Brain Stimulation (DBS) of the subthalamic nucleus and of vision.

Methods: We studied 10 patients with idiopathic PD, who were responsive to -Dopa and had more than 1 year use of bilateral subthalamic nucleus stimulation. The patients did not have to display visible tremor to be included in the study. Tremor was recorded with two objective methods, a force platform and a 3 dimensional (3D) motion capture system that tracked movements in four key proximal sections of the body (knee, hip, shoulder and head). They were assessed after an overnight withdrawal of anti-PD medications with DBS ON and OFF and with eyes open and closed during unperturbed and perturbed stance with randomized calf vibration, using a randomized test order design.

Results: Tremor was detected with the Unified Parkinson's Disease Rating Scale (UPDRS) in 6 of 10 patients but only distally (hands and feet) with DBS OFF. With the force platform and the 3D motion capture system, tremor was detected in 6 of 10 and 7 of 10 patients respectively, mostly in DBS OFF but also with DBS ON in some patients. The 3D motion capture system revealed that more than one body section was usually affected by tremor and that the tremor amplitude was non-uniform, but the frequency almost identical, across sites. DBS reduced tremor amplitude non-uniformly across the body. Visual input mostly reduced tremor amplitude with DBS ON.

Conclusions: Technical recording methods offer objective and sensitive detection of tremor that provide detailed characteristics such as peak amplitude, frequency and distribution pattern, and thus, provide information that can guide the optimization of treatments. Both methods detected the effects of DBS and visual input but the 3D motion system was more versatile in that it could detail the presence and properties of tremor at individual body sections.
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http://dx.doi.org/10.1186/s12984-020-00677-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183594PMC
April 2020

Inner ear is a target for insulin signaling and insulin resistance: evidence from mice and auditory HEI-OC1 cells.

BMJ Open Diabetes Res Care 2020 03;8(1)

Experimental Medical Science, Section for Diabetes, Metabolism and Endocrinology, Lund University Diabetes Centre, Lund University, Lund, Sweden

Objective: The mechanisms underlying the association between diabetes and inner ear dysfunction are not known yet. The aim of the present study is to evaluate the impact of obesity/insulin resistance on inner ear fluid homeostasis in vivo, and to investigate whether the organ of Corti could be a target tissue for insulin signaling using auditory House Ear Institute-Organ of Corti 1 (HEI-OC1) cells as an in vitro model.

Methods: High fat diet (HFD) fed C57BL/6J mice were used as a model to study the impact of insulin resistance on the inner ear. In one study, 12 C57BL/6J mice were fed either control diet or HFD and the size of the inner ear endolymphatic fluid compartment (EFC) was measured after 30 days using MRI and gadolinium contrast as a read-out. In another study, the size of the inner ear EFC was evaluated in eight C57BL/6J mice both before and after HFD feeding, with the same techniques. HEI-OC1 auditory cells were used as a model to investigate insulin signaling in organ of Corti cells.

Results: HFD feeding induced an expansion of the EFC in C57BL/6J mice, a hallmark of inner ear dysfunction. Insulin also induced phosphorylation of protein kinase B (PKB/Akt) at Ser473, in a PI3-kinase-dependent manner. The phosphorylation of PKB was inhibited by isoproterenol and IBMX, a general phosphodiesterase (PDE) inhibitor. PDE1B, PDE4D and the insulin-sensitive PDE3B were found expressed and catalytically active in HEI-OC1 cells. Insulin decreased and AICAR, an activator of AMP-activated protein kinase, increased the phosphorylation at the inhibitory Ser79 of acetyl-CoA carboxylase, the rate-limiting enzyme in de novo lipogenesis. Furthermore, the activity of hormone-sensitive lipase, the rate-limiting enzyme in lipolysis, was detected in HEI-OC1 cells.

Conclusions: The organ of Corti could be a target tissue for insulin action, and inner ear insulin resistance might contribute to the association between diabetes and inner ear dysfunction.
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http://dx.doi.org/10.1136/bmjdrc-2019-000820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170413PMC
March 2020

PET Visualized Stimulation of the Vestibular Organ in Menière's Disease.

Front Neurol 2020 28;11:11. Epub 2020 Jan 28.

Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

The cortical metabolic activity in patients with Menière's disease has not been investigated. The aim of this study was to investigate the F-FDG cerebral uptake in Menière's patients compared to healthy controls. Eight patients with right-sided Menière's disease and fourteen healthy controls underwent a video head impulse test (vHIT), test of utricular function with ocular vestibular evoked myogenic potentials (oVEMP) and three F-FDG-based PET examinations of the brain. Participants were seated in a self-propelled chair, injected with F-FDG and then exposed to 35 min of chair motion stimulation, followed by a PET scan. Two types of natural vestibular stimuli were applied, predominantly toward the right horizontal semicircular canal (angular acceleration) and right utriculus (linear acceleration). For baseline scans, participants were injected with F-FDG while seated without movement. Analyses of baseline scans revealed decreased F-FDG-uptake in the medial part of Heschl's gyrus in the left hemisphere in patients with Menière's disease compared to healthy controls. During angular vestibular stimulation there was also a significantly decreased F-FDG uptake in the intersection between the medial part of Heschl's gyrus and the parietal operculum in the left hemisphere and bilaterally in the posterior part of insula. During linear stimulation, Menière's patients showed decreased F-FDG uptake in the medial part of Heschl's gyrus in the right hemisphere and also bilaterally in the posterior insula. In addition, decreased F-FDG uptake was seen in the thalamus during vestibular stimulation. Heschl's gyrus, the posterior part of insula, and thalamus have previously been shown to be core areas for processing vestibular inputs. Patients with Menière's disease solely differed from the healthy controls with lower cortical activity in these areas at baseline and during natural vestibular stimulation.
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http://dx.doi.org/10.3389/fneur.2020.00011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997538PMC
January 2020

Dizziness and localized pain are often concurrent in patients with balance or psychological disorders.

Scand J Pain 2020 04;20(2):353-362

Department of Clinical Sciences, Lund University, S-221 85 Lund, Sweden, Fax: +46 46 211 09 68.

Background and aims Symptoms of dizziness and pain are both common complaints and the two symptoms often seem to coincide. When symptoms appear concomitant for sustained periods of time the symptoms might maintain and even exacerbate each other, sometimes leading to psychological distress. In order to evaluate such comorbidity we studied patients referred to a vestibular unit and to a psychiatric outpatient clinic with respectively balance disorders and psychological issues. Methods Consecutive patients referred to a vestibular unit (n = 49) and a psychiatric outpatient clinic (n = 62) answered the Dizziness Handicap Inventory (DHI) questionnaire and a questionnaire detailing occurrence of dizziness and pain. Results The experience of dizziness and pain often coincided within individuals across both clinical populations, especially if the pain was located to the neck/shoulder or the back (p = 0.006). Patients who reported dizziness had significantly more often pain (p = 0.024); in the head (p = 0.002), neck/shoulders (p = 0.003) and feet (p = 0.043). Moreover, patients who reported dizziness stated significantly higher scoring on emotional (p < 0.001) and functional (p < 0.001) DHI sub-scales. Furthermore, patients who reported an accident in their history suffered significantly more often from dizziness (p = 0.039) and pain (p < 0.001); in the head (p < 0.001), neck/shoulders (p < 0.001) and arms (p = 0.045) and they scored higher on the emotional (p = 0.004) and functional (p = 0.002) DHI sub-scales. Conclusions The findings suggest comorbidity to exist between dizziness and neck/shoulder or back pain in patients seeking health care for balance disorders or psychological issues. Patients suffering from dizziness and pain, or with both symptoms, also reported higher emotional and functional strain. Thus, healthcare professionals should consider comorbidity when determining diagnosis and consequent measures. Implications Clinicians need to have a broader "receptive scope" in both history and clinical examinations, and ask for all symptoms. Although the patients in this study visited a vestibular unit respectively a psychological clinic, they commonly reported pain conditions when explicitly asked for this symptom. A multimodal approach is thus to favor, especially when the symptoms persist, for the best clinical management.
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http://dx.doi.org/10.1515/sjpain-2019-0121DOI Listing
April 2020

From cytogenetics to cytogenomics: whole-genome sequencing as a first-line test comprehensively captures the diverse spectrum of disease-causing genetic variation underlying intellectual disability.

Genome Med 2019 11 7;11(1):68. Epub 2019 Nov 7.

Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.

Background: Since different types of genetic variants, from single nucleotide variants (SNVs) to large chromosomal rearrangements, underlie intellectual disability, we evaluated the use of whole-genome sequencing (WGS) rather than chromosomal microarray analysis (CMA) as a first-line genetic diagnostic test.

Methods: We analyzed three cohorts with short-read WGS: (i) a retrospective cohort with validated copy number variants (CNVs) (cohort 1, n = 68), (ii) individuals referred for monogenic multi-gene panels (cohort 2, n = 156), and (iii) 100 prospective, consecutive cases referred to our center for CMA (cohort 3). Bioinformatic tools developed include FindSV, SVDB, Rhocall, Rhoviz, and vcf2cytosure.

Results: First, we validated our structural variant (SV)-calling pipeline on cohort 1, consisting of three trisomies and 79 deletions and duplications with a median size of 850 kb (min 500 bp, max 155 Mb). All variants were detected. Second, we utilized the same pipeline in cohort 2 and analyzed with monogenic WGS panels, increasing the diagnostic yield to 8%. Next, cohort 3 was analyzed by both CMA and WGS. The WGS data was processed for large (> 10 kb) SVs genome-wide and for exonic SVs and SNVs in a panel of 887 genes linked to intellectual disability as well as genes matched to patient-specific Human Phenotype Ontology (HPO) phenotypes. This yielded a total of 25 pathogenic variants (SNVs or SVs), of which 12 were detected by CMA as well. We also applied short tandem repeat (STR) expansion detection and discovered one pathologic expansion in ATXN7. Finally, a case of Prader-Willi syndrome with uniparental disomy (UPD) was validated in the WGS data. Important positional information was obtained in all cohorts. Remarkably, 7% of the analyzed cases harbored complex structural variants, as exemplified by a ring chromosome and two duplications found to be an insertional translocation and part of a cryptic unbalanced translocation, respectively.

Conclusion: The overall diagnostic rate of 27% was more than doubled compared to clinical microarray (12%). Using WGS, we detected a wide range of SVs with high accuracy. Since the WGS data also allowed for analysis of SNVs, UPD, and STRs, it represents a powerful comprehensive genetic test in a clinical diagnostic laboratory setting.
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http://dx.doi.org/10.1186/s13073-019-0675-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836550PMC
November 2019

Positron emission tomography visualized stimulation of the vestibular organ is localized in Heschl's gyrus.

Hum Brain Mapp 2020 01 14;41(1):185-193. Epub 2019 Sep 14.

Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, Aarhus, Denmark.

The existence of a human primary vestibular cortex is still debated. Current knowledge mainly derives from functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) acquisitions during artificial vestibular stimulation. This may be problematic as artificial vestibular stimulation entails coactivation of other sensory receptors. The use of fMRI is challenging as the strong magnetic field and loud noise during MRI may both stimulate the vestibular organ. This study aimed to characterize the cortical activity during natural stimulation of the human vestibular organ. Two fluorodeoxyglucose (FDG)-PET scans were obtained after natural vestibular stimulation in a self-propelled chair. Two types of stimuli were applied: (a) rotation (horizontal semicircular canal) and (b) linear sideways movement (utriculus). A comparable baseline FDG-PET scan was obtained after sitting motion-less in the chair. In both stimulation paradigms, significantly increased FDG uptake was measured bilaterally in the medial part of Heschl's gyrus, with some overlap into the posterior insula. This is the first neuroimaging study to visualize cortical processing of natural vestibular stimuli. FDG uptake was demonstrated in the medial-most part of Heschl's gyrus, normally associated with the primary auditory cortex. This anatomical localization seems plausible, considering that the labyrinth contains both the vestibular organ and the cochlea.
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http://dx.doi.org/10.1002/hbm.24798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268041PMC
January 2020

Stress Levels Escalate When Repeatedly Performing Tasks Involving Threats.

Front Psychol 2019 4;10:1562. Epub 2019 Jul 4.

Lund University Humanities Lab, Lund, Sweden.

Police work may include performing repeated tasks under the influence of psychological stress, which can affect perceptual, cognitive and motor performance. However, it is largely unknown how repeatedly performing stressful tasks physically affect police officers in terms of heart rate and pupil diameter properties. Psychological stress is commonly assessed by monitoring the changes in these biomarkers. Heart rate and pupil diameter was measured in 12 male police officers when performing a sequence of four stressful tasks, each lasting between 20 and 130 s. The participants were first placed in a dimly illuminated anteroom before allowed to enter a brightly lit room where a scenario was played out. After each task was performed, the participants returned to the anteroom for about 30 s before performing the next sequential task. Performing a repeated sequence of stressful tasks caused a significant increase in heart rate ( = 0.005). The heart rate started to increase already before entering the scenario room and was significantly larger just after starting the task than just before starting the task ( < 0.001). This pattern was more marked during the first tasks ( < 0.001). Issuance of a verbal "abort" command which terminated the tasks led to a significant increase of heart rate ( = 0.002), especially when performing the first tasks ( = 0.002). The pupil diameter changed significantly during the repeated tasks during all phases but in a complex pattern where the pupil diameter reached a minimum during task 2 followed by an increase during tasks 3 and 4 ( ≤ 0.020). During the initial tasks, the pupil size ( = 0.014) increased significantly. The results suggest that being repeatedly exposed to stressful tasks can produce in itself an escalation of psychological stress, this even prior to being exposed to the task. However, the characteristics of both the heart rate and pupil diameter were complex, thus, the findings highlight the importance of studying the effects and dynamics of different stress-generating factors. Monitoring heart rate was found useful to screen for stress responses, and thus, to be a vehicle for indication if and when rotation of deployed personnel is necessary to avoid sustained high stress exposures.
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http://dx.doi.org/10.3389/fpsyg.2019.01562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6621421PMC
July 2019

Presbyvestibulopathy: Diagnostic criteria Consensus document of the classification committee of the Bárány Society.

J Vestib Res 2019;29(4):161-170

Department of Neurology and German Center for Vertigo, Ludwig Maximilians University, Munich, Germany.

This paper describes the diagnostic criteria for presbyvestibulopathy (PVP) by the Classification Committee of the Bárány Society. PVP is defined as a chronic vestibular syndrome characterized by unsteadiness, gait disturbance, and/or recurrent falls in the presence of mild bilateral vestibular deficits, with findings on laboratory tests that are between normal values and thresholds established for bilateral vestibulopathy.The diagnosis of PVP is based on the patient history, bedside examination and laboratory evaluation. The diagnosis of PVP requires bilaterally reduced function of the vestibulo-ocular reflex (VOR). This can be diagnosed for the high frequency range of the VOR with the video-HIT (vHIT); for the middle frequency range with rotary chair testing; and for the low frequency range with caloric testing.For the diagnosis of PVP, the horizontal angular VOR gain on both sides should be < 0.8 and > 0.6, and/or the sum of the maximal peak velocities of the slow phase caloric-induced nystagmus for stimulation with warm and cold water on each side should be < 25°/s and > 6°/s, and/or the horizontal angular VOR gain should be > 0.1 and < 0.3 upon sinusoidal stimulation on a rotatory chair.PVP typically occurs along with other age-related deficits of vision, proprioception, and/or cortical, cerebellar and extrapyramidal function which also contribute and might even be required for the manifestation of the symptoms of unsteadiness, gait disturbance, and falls. These criteria simply consider the presence of these symptoms, along with documented impairment of vestibular function, in older adults.
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http://dx.doi.org/10.3233/VES-190672DOI Listing
June 2020

Endolymphatic hydrops induced by different mechanisms responds differentially to spironolactone: a rationale for understanding the diversity of treatment responses in hydropic inner ear disease.

Acta Otolaryngol 2019 Aug 30;139(8):685-691. Epub 2019 May 30.

c Department of Clinical Sciences, Section for Otorhinolaryngology , Lund University & Skåne University Hospital , Lund , Sweden.

The exact pathophysiological mechanism(s) underlying endolymphatic hydrops (EH) remain elusive. We have previously shown that chronic administration of vasopressin and inhibitors of the cAMP/cGMP degrading enzymes (PDE3, PDE4, PDE5) results in the development of EH to mice. Evaluate the ability of spironolactone, an aldosterone antagonist, to prevent EH, when induced by different pathways. Mice were treated for 4 weeks with vasopressin, the PDE3 inhibitor cilostamide and the PDE4 inhibitor rolipram in the presence or absence of spironolactone. EH was assessed using high resolution 9.4T MRI. The expression of proteins in human saccule sensory epithelium was studied with immunohistochemistry. Spironolactone prevents EH induced by vasopressin and rolipram, but not hydrops induced by cilostamide. The aldosterone target ENaC and the mineralocorticoid receptor were expressed in the human saccule sensory epithelium. The effect of spironolactone on EH appears to be pathway-dependent and may provide explanations why certain drugs may be effective in some patients with hydropic ear disease while not in others. Extrapolating this finding to the clinic supports that a personalized medicine approach is probably necessary in the treatment of diseases involving EH, as different pathways may be needed to be targeted for treatment.
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http://dx.doi.org/10.1080/00016489.2019.1616819DOI Listing
August 2019

Different Visual Weighting due to Fast or Slow Vestibular Deafferentation: Before and after Schwannoma Surgery.

Neural Plast 2019 18;2019:4826238. Epub 2019 Feb 18.

Department of Otorhinolaryngology Head and Neck Surgery, Clinical Sciences, Skåne University Hospital, S-221 85 Lund, Sweden.

Background: Feedback postural control depends upon information from somatosensation, vision, and the vestibular system that are weighted depending on their relative importance within the central nervous system. Following loss of any sensory component, the weighting changes, e.g., when suffering a vestibular loss, the most common notion is that patients become more dependent on visual cues for maintaining postural control. Dizziness and disequilibrium are common after surgery in schwannoma patients, which could be due to interpretation of the remaining sensory systems involved in feedback-dependent postural control and spatial orientation.

Objective: To compare visual dependency in spatial orientation and postural control in patients suffering from unilateral vestibular loss within different time frames.

Methods: Patients scheduled for schwannoma surgery: group 1 ( = 27) with no vestibular function prior to surgery (lost through years), group 2 ( = 12) with remaining vestibular function at the time of surgery (fast deafferentation), and group 3 ( = 18) with remaining function that was lost through gentamicin installations in the middle ear (slow deafferentation). All patients performed vibratory posturography and rod and frame investigation before surgery and 6 months after surgery.

Results: Postural control improved after surgery in patients that suffered a slow deafferentation (groups 1 and 3) ( < 0.001). Patients that suffered fast loss of remaining vestibular function (group 2) became less visual field dependent after surgery ( ≤ 0.035) and were less able to maintain stability compared with group 1 ( = 0.010) and group 3 ( = 0.010).

Conclusions: The nature and time course of vestibular deafferentation influence the weighting of remaining sensory systems in order to maintain postural control and spatial orientation.
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http://dx.doi.org/10.1155/2019/4826238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398006PMC
May 2019

Postural instability in an immersive Virtual Reality adapts with repetition and includes directional and gender specific effects.

Sci Rep 2019 02 28;9(1):3168. Epub 2019 Feb 28.

Department of Health Sciences/Physiotherapy, Lund University, Lund, Sweden.

The ability to handle sensory conflicts and use the most appropriate sensory information is vital for successful recovery of human postural control after injury. The objective was to determine if virtual reality (VR) could provide a vehicle for sensory training, and determine the temporal and spatial nature of such adaptive changes. Twenty healthy subjects participated in the study (10 females). The subjects watched a 90-second VR simulation of railroad (rollercoaster) motion in mountainous terrain during five repeated simulations, while standing on a force platform that recorded their stability. The immediate response to watching the VR movie was an increased level of postural instability. Repeatedly watching the same VR movie significantly reduced both the anteroposterior (62%, p < 0.001) and lateral (47%, p = 0.001) energy used. However, females adapted more slowly to the VR stimuli as reflected by higher use of total (p = 0.007), low frequency (p = 0.027) and high frequency (p = 0.026) energy. Healthy subjects can significantly adapt to a multidirectional, provocative, visual environment after 4-5 repeated sessions of VR. Consequently, VR technology might be an effective tool for rehabilitation involving visual desensitisation. However, some females may require more training sessions to achieve effects with VR.
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http://dx.doi.org/10.1038/s41598-019-39104-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395702PMC
February 2019

Steroids for Acute Vestibular Neuronitis-the Earlier the Treatment, the Better the Outcome?

Otol Neurotol 2019 03;40(3):372-374

Department of OtoRhinoLaryngology, Head and Neck Surgery, Clinical Sciences Lund University, Skåne University Hospital, Lund, Sweden.

Objective: To present findings that suggest steroid treatment within 24 hours of onset of vestibular neuronitis results in better restitution of vestibular function than treatment between 25 and 72 hours.

Patients: Thirty-three consecutive patients (17 men, 16 women, mean age 57 yr, range 17-85 yr) with acute vestibular neuronitis and treated with steroids within 72 hours after symptom onset. Patients were divided into two groups depending on if they were treated within the first 24 hours or not.

Interventions: Oral prednisolone 50 mg/d for 5 days with tapering of doses for the next 5 days, or combined with initial intravenous betamethasone 8 mg the first 1 to 2 days if the patient was nauseous.

Main Outcome Measures: Proportion of patients with normal caloric test result (canal paresis value < 32%) at follow-up after 3 or 12 months.

Results: All 9 patients (100%) treated within 24 hours from onset of vestibular neuronitis had normal caloric test results at follow-up after 3 months, as compared with 14 of 24 (58%) of the patients treated between 25 and 72 hours (p < 0,05, Fisher's exact test).

Conclusions: The timing of steroid treatment of vestibular neuronitis may be of importance for subsequent vestibular restitution, and hence, for both time to recovery and late symptoms according to the literature.
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http://dx.doi.org/10.1097/MAO.0000000000002106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380443PMC
March 2019

Functional Head Impulse Testing Might Be Useful for Assessing Vestibular Compensation After Unilateral Vestibular Loss.

Front Neurol 2018 19;9:979. Epub 2018 Nov 19.

Department of Clinical Sciences Lund, Faculty of Medicine, Skåne University Hospital, Lund University, Lund, Sweden.

Loss of the vestibulo-ocular reflex (VOR) affects visual acuity during head movements. Previous studies have shown that compensatory eye-saccades improve visual acuity and that the timing of the saccade is important. Most of the tests involved in testing VOR are made with passive head movement, that do not necessarily reflect the activities of daily living and thus not being proportionate to symptoms and distresses of the patients. To examine differences between active (self-generated) or passive (imposed by the examiner) head rotations while trying to maintain visual focus on a target. Nine subjects with unilateral total vestibular loss were recruited (4 men and 5 women, mean age 47) and tested with video Head Impulse Test (vHIT) and Head Impulse Testing Device-Functional Test (HITD-FT) during passive and active movements while looking at a target. VOR gain, latencies of covert saccades, frequency of covert saccades and visual acuity were measured and analyzed. Active head-impulses toward the lesioned side resulted in better visual acuity ( = 0.002) compared to conventional passive head-impulses and generated eye-saccades with significantly shorter latencies ( = 0.004). Active movements to the lesioned side generated dynamic visual acuities that were as good as when testing the intact side. Actively generated head impulses resulted in normal dynamic visual acuity, even when performed toward the side of total vestibular loss. This might be attributed to the appearance of short-latency covert saccades. The results show a strong relationship between self-generated movements, latencies of covert saccades and outcome in HITD-FT, i.e., a better dynamic visual function with less retinal slip which is the main function of the VOR. The method of active HITD-FT might be valuable in assessing vestibular compensation and monitoring ongoing vestibular rehabilitation.
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http://dx.doi.org/10.3389/fneur.2018.00979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252383PMC
November 2018

European Position Statement on Diagnosis, and Treatment of Meniere's Disease.

J Int Adv Otol 2018 Aug;14(2):317-321

Universita degli Studi di Siena, Siena, Italy.

Meniere Disease keeps challenges in its diagnosis and treatment since was defined by Prosper Meniere at the beginning of 19th Century. Several classifications and definition were made until now and speculations still exist on its etiology. As the etiology remains speculative the treatment models remain in discussion also. The European Academy of Otology and Neurotology Vertigo Guidelines Study Group intended to work on the diagnosis and treatment of Meniere's disease and created the European Positional Statement Document also by resuming the consensus studies on it. The new techniques on diagnosis are emphasized as well as the treatment models for each stage of the disease are clarified by disregarding the dilemmas on its treatment. The conservative, noninvasive and invasive therapeutic models are highlighted.
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http://dx.doi.org/10.5152/iao.2018.140818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354459PMC
August 2018

Asking about dizziness when turning in bed predicts examination findings for benign paroxysmal positional vertigo.

J Vestib Res 2018 ;28(3-4):339-347

Department of Otorhinolaryngology Head and Neck Surgery, Clinical Sciences, Lund, Sweden.

Background: Benign paroxysmal positional vertigo (BPPV) is the single most common cause of vestibular vertigo and is characterised by short episodes of rotational vertigo precipitated by changes in head positions like lying down or turning in bed.

Objective: This study aims to assess useful questions when suspecting benign paroxysmal positional vertigo (BPPV) caused dizziness as well as identifying if a single question can be useful in identify or distinguish patients with BPPV from other dizziness aetiology.

Method: A total of 149 patients admitted due to dizziness were included. Patients answered a questionnaire and were investigated for BPPV with diagnostic manoeuvres.

Result: Two of the 15 questions were of diagnostic importance. Dizziness when laying down or turning in bed, increased likelihood of BPPV by an odds ratio (95% confidence interval) of 60 (7.47-481.70). Continuous dizziness duration as opposed to lasting seconds decreased likelihood of BPPV with an odds ratio of 0.06 (0.01-0.27).

Conclusion: Vertiginous attacks by turning or laying down in bed together with dizziness <1 minute, are important questions and strongly related to BPPV. Such questions are important when taking a medical history and may help to early identify BPPV, also for non-medical staff, as well as reduce the need of further investigations.
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http://dx.doi.org/10.3233/VES-180637DOI Listing
November 2019

Pólya Urn Latent Dirichlet Allocation: A Doubly Sparse Massively Parallel Sampler.

IEEE Trans Pattern Anal Mach Intell 2019 Jul 4;41(7):1709-1719. Epub 2018 Jun 4.

Latent Dirichlet Allocation (LDA) is a topic model widely used in natural language processing and machine learning. Most approaches to training the model rely on iterative algorithms, which makes it difficult to run LDA on big corpora that are best analyzed in parallel and distributed computational environments. Indeed, current approaches to parallel inference either don't converge to the correct posterior or require storage of large dense matrices in memory. We present a novel sampler that overcomes both problems, and we show that this sampler is faster, both empirically and theoretically, than previous Gibbs samplers for LDA. We do so by employing a novel Pólya-urn-based approximation in the sparse partially collapsed sampler for LDA. We prove that the approximation error vanishes with data size, making our algorithm asymptotically exact, a property of importance for large-scale topic models. In addition, we show, via an explicit example, that-contrary to popular belief in the topic modeling literature-partially collapsed samplers can be more efficient than fully collapsed samplers. We conclude by comparing the performance of our algorithm with that of other approaches on well-known corpora.
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http://dx.doi.org/10.1109/TPAMI.2018.2832641DOI Listing
July 2019
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