Electroencephalography Signatures for Conditioned Pain Modulation and Pain Perception in Nonspecific Chronic Low Back Pain-An Exploratory Study.

Conditioned pain modulation (CPM) can discriminate between healthy and chronic pain patients. However, its relationship with neurophysiological pain mechanisms is poorly understood. Brain oscillations measured by electroencephalography (EEG) might help gain insight into this complex relationship. OBJECTIVE: To investigate the relationship between CPM response and self-reported pain intensity in non-specific chronic low back pain (NSCLBP) and explore respective EEG signatures associated to these mechanisms. DESIGN: Cross-sectional analysis. PARTICIPANTS: Thirty NSCLBP patients participated. METHODS: Self-reported low back pain, questionnaires, mood scales, CPM (static and dynamic quantitative sensory tests), and resting surface EEG data were collected and analyzed. Linear regression models were used for statistical analysis. RESULTS: CPM was not significantly correlated with self-reported pain intensity scores. Relative power of EEG in the beta and high beta bands as recorded from the frontal, central, and parietal cortical areas were significantly associated with CPM. EEG relative power at delta and theta bands as recorded from the central area were significantly correlated with self-reported pain intensity scores while controlling for self-reported depression. CONCLUSIONS: Faster EEG frequencies recorded from pain perception areas may provide a signature of a potential cortical compensation caused by chronic pain states. Slower EEG frequencies may have a critical role in abnormal pain processing.

Loop characteristics and audio-vestibular symptoms or hemifacial spasm: is there a correlation? A multiplanar MRI study.

AIM: We investigated if loop characteristics correlate with audio-vestibular symptoms or hemifacial spasm in patients with a vascular loop in the root entry zone (VII and VIII) and in the internal auditory canal. MATERIALS AND METHODS: A retrospective, multicenter study analyzed 2622 consecutive magnetic resonance imaging (MRI) scans of the cerebellopontine angle of patients with asymmetric audio-vestibular symptom or hemifacial spasm; patients' symptoms were confirmed by clinical tests. MRIs displaying vascular loops visible in the axial view were analyzed using multiplanar reconstruction. We evaluated (1) depth of penetration of the loop into the internal auditory canal (IAC); (2) largest diameter of the vessel; (3) nerve(s) involved in the vascular impingement, position of the loop relative to such nerve(s) and number of contacts between vessel and nerve(s); (4) length of such contact. The loop metrics described above were correlated with the patients' audio-vestibular symptoms and hemifacial spasm. RESULTS: Three hundred ninety-nine patients displayed a loop visible in the MRI axial view and out of them only 118 displayed a direct contact between loop and nerve. The cochlear nerve was involved in a contact in 57.7%. Loops in direct nerve contact had a calibre > 0.85 mm, were located in the middle portion of the IAC, and correlated with vertigo (p = 0.002), tinnitus (p = 0.003), and hemifacial spasm (p < 0.001). Asymmetric sensorineural hearing loss (SNHL) correlated with number of contacts (p < 0.001) and length of contact (p < 0.05). The contact was asymptomatic in 41.5% of patients. CONCLUSION: Loop characteristics may help predict whether a vascular impingement is responsible for a symptom and guide the physician to select the best treatment. KEY POINTS: • A vascular loop in the internal auditory canal was observed in 18-20% of the patients in this study; whether a loop can be responsible for a compressive syndrome is still unclear in particular referred to the vestibulocochlear nerve. • Compression by a loop on the facial nerve causes hemifacial spasm; compression by a loop on the cochlear or vestibular nerve may cause audio-vestibular symptoms. • In patients with a loop, the loop calibre, the loop position, and the number of loop-nerve(s) assessed via the multiplanar MRI reconstruction technique may help assess whether the patient will manifest audio-vestibular symptoms or hemifacial spasm.

Can miR-34a be suitable for monitoring sensorineural hearing loss in patients with mitochondrial disease? A case series.

Purpose: We aimed at evaluating the feasibility of using MicroRNA (miR)-34a and miR-29b to detect inner ear damage in patients with mitochondrial disease (MD) and sensorineural hearing loss (SNHL).Material and Methods: Three patients with MD and SNHL and seven healthy control subjects were included in this case series. MD patients underwent pure tone audiometry (PTA), distortion product otoacoustic emission (DPOAE) and auditory brain response tests to investigate the specific cochlear and retrocochlear functions; control patients underwent PTA. MiR-34a and miR-29b were extracted from blood in all subjects included in the study. The expression of miR-34a and miR-29b in MD patients and healthy controls were statistically compared, then the expression of these two miRs was compared with DPOAE values.Results: In MD patients, miR-34a was significantly up-regulated compared to healthy controls; miR-34a and DPOAEs were negatively correlated. Conversely, miR-29b was up-regulated only in the youngest patient who suffered from the mildest forms of MD and SNHL, and negatively correlated with DPOAEs.Conclusion: In MD patients, miR-34a and miR-29b might be a marker of inner ear damage and early damage, respectively. Additional studies on larger samples are necessary to confirm these preliminary results.

Voice Parameter Changes in Professional Musician-Singers Singing with and without an Instrument: The Effect of Body Posture.

BACKGROUND AND AIM: The impact of body posture on vocal emission is well known. Postural changes may increase muscular resistance in tracts of the phono-articulatory apparatus and lead to voice disorders. This work aimed to assess whether and to which extent body posture during singing and playing a musical instrument impacts voice performance in professional musicians. SUBJECTS AND METHODS: Voice signals were recorded from 17 professional musicians (pianists and guitarists) while they were singing and while they were singing and playing a musical instrument simultaneously. Metrics were extracted from their voice spectrogram using the Multi-Dimensional Voice Program (MDVP) and included jitter, shift in fundamental voice frequency (sF0), shimmer, change in peak amplitude, noise to harmonic ratio, Voice Turbulence Index, Soft Phonation Index (SPI), Frequency Tremor Intensity Index, Amplitude Tremor Intensity Index, and maximum phonatory time (MPT). Statistical analysis was performed using two-tailed t tests, one-way ANOVA, and χ2 tests. Subjects' body posture was visually assessed following the recommendations of the Italian Society of Audiology and Phoniatrics. Thirty-seven voice signals were collected, 17 during singing and 20 during singing and playing a musical instrument. RESULTS: Data showed that playing an instrument while singing led to an impairment of the "singer formant" and to a decrease in jitter, sF0, shimmer, SPI, and MPT. However, statistical analysis showed that none of the MDVP metrics changed significantly when subjects played an instrument compared to when they did not. Shoulder and back position affected voice features as measured by the MDVP metrics, while head and neck position did not. In particular, playing the guitar decreased the amplitude of the "singer formant" and increased noise, causing a typical "raucous rock voice." CONCLUSIONS: Voice features may be affected by the use of the instrument the musicians play while they sing. Body posture selected by the musician while playing the instrument may affect expiration and phonation.

Can the Jankovic-assessment be used as an alternative to electromyography? A cross-sectional study on facial dystonia patients treated with Botulinum toxin.

PURPOSE: This study aims to quantitatively compare the Jankovic assessment (JA) with electromyography (EMG)-based measures for assessing changes in facial movements in patients with facial dystonia. MATERIALS AND METHODS: Thirteen patients (five males and eight females) affected with different forms of facial dystonia (hemifacial spasm and synkinesis) participated in this study. All patients were treated with Botulinum Toxin (BTX) and evaluated with the JA scale and EMG-based measures, including motor unit potentials (MUP) latency and presence of polyphasic potentials before and after BTX injection. Correlation between the JA scores and the EMG-based measures was calculated. Statistical analysis was performed with the Pearson test. RESULTS: Correlation between the JA scores and the EMG-based measures was found to be statistically significant, both before and after treatment with BTX. CONCLUSION AND RELEVANCE: JA scores significantly correlated with more objective EMG-based measures, suggesting that the JA scale can be used to assess facial movement changes, for example elicited by a treatment such as BTX injection. Thus, in facial dystonia patients, the JA scale may be used for evaluating treatment outcomes as a valid and low-cost alternative to EMG.

Working Memory Function in Children with Single Side Deafness Using a Bone-Anchored Hearing Implant: A Case-Control Study.

The importance of a good hearing function to preserve memory and cognitive abilities has been shown in the adult population, but studies on the pediatric population are currently lacking. This study aims at evaluating the effects of a bone-anchored hearing implant (BAHI) on speech perception, speech processing, and memory abilities in children with single side deafness (SSD). We enrolled n = 25 children with SSD and assessed them prior to BAHI implantation, and at 1-month and 3-month follow-ups after BAHI implantation using tests of perception in silence and perception in phonemic confusion, dictation in silence and noise, and working memory and short-term memory function in conditions of silence and noise. We also enrolled and evaluated n = 15 children with normal hearing. We found a statistically significant difference in performance between healthy children and children with SSD before BAHI implantation in the scores of all tests. After 3 months from BAHI implantation, the per-formance of children with SSD was comparable to that of healthy subjects as assessed by tests of speech perception, working memory, and short-term memory function in silence condition, while differences persisted in the scores of the dictation test (both in silence and noise conditions) and of the working memory function test in noise condition. Our data suggest that in children with SSD BAHI improves speech perception and memory. Speech rehabilitation may be necessary to further improve speech processing.

Spatiotemporal dynamics of online motor correction processing revealed by high-density electroencephalography.

The ability to control online motor corrections is key to dealing with unexpected changes arising in the environment with which we interact. How the CNS controls online motor corrections is poorly understood, but evidence has accumulated in favor of a submovement-based model in which apparently continuous movement is segmented into distinct submovements. Although most studies have focused on submovements' kinematic features, direct links with the underlying neural dynamics have not been extensively explored. This study sought to identify an electroencephalographic signature of submovements. We elicited kinematic submovements using a double-step displacement paradigm. Participants moved their wrist toward a target whose direction could shift mid-movement with a 50% probability. Movement kinematics and cortical activity were concurrently recorded with a low-friction robotic device and high-density electroencephalography. Analysis of spatiotemporal dynamics of brain activation and its correlation with movement kinematics showed that the production of each kinematic submovement was accompanied by (1) stereotyped topographic scalp maps and (2) frontoparietal ERPs time-locked to submovements. Positive ERP peaks from frontocentral areas contralateral to the moving wrist preceded kinematic submovement peaks by 220-250 msec and were followed by positive ERP peaks from contralateral parietal areas (140-250 msec latency, 0-80 msec before submovement peaks). Moreover, individual subject variability in the latency of frontoparietal ERP components following the target shift significantly predicted variability in the latency of the corrective submovement. Our results are in concordance with evidence for the intermittent nature of continuous movement and elucidate the timing and role of frontoparietal activations in the generation and control of corrective submovements.

Robotic measurement of arm movements after stroke establishes biomarkers of motor recovery.

BACKGROUND AND PURPOSE: Because robotic devices record the kinematics and kinetics of human movements with high resolution, we hypothesized that robotic measures collected longitudinally in patients after stroke would bear a significant relationship to standard clinical outcome measures and, therefore, might provide superior biomarkers. METHODS: In patients with moderate-to-severe acute ischemic stroke, we used clinical scales and robotic devices to measure arm movement 7, 14, 21, 30, and 90 days after the event at 2 clinical sites. The robots are interactive devices that measure speed, position, and force so that calculated kinematic and kinetic parameters could be compared with clinical assessments. RESULTS: Among 208 patients, robotic measures predicted well the clinical measures (cross-validated R(2) of modified Rankin scale=0.60; National Institutes of Health Stroke Scale=0.63; Fugl-Meyer=0.73; Motor Power=0.75). When suitably scaled and combined by an artificial neural network, the robotic measures demonstrated greater sensitivity in measuring the recovery of patients from day 7 to day 90 (increased standardized effect=1.47). CONCLUSIONS: These results demonstrate that robotic measures of motor performance will more than adequately capture outcome, and the altered effect size will reduce the required sample size. Reducing sample size will likely improve study efficiency.

Impact of brain tissue filtering on neurostimulation fields: a modeling study.

Electrical neurostimulation techniques, such as deep brain stimulation (DBS) and transcranial magnetic stimulation (TMS), are increasingly used in the neurosciences, e.g., for studying brain function, and for neurotherapeutics, e.g., for treating depression, epilepsy, and Parkinson's disease. The characterization of electrical properties of brain tissue has guided our fundamental understanding and application of these methods, from electrophysiologic theory to clinical dosing-metrics. Nonetheless, prior computational models have primarily relied on ex-vivo impedance measurements. We recorded the in-vivo impedances of brain tissues during neurosurgical procedures and used these results to construct MRI guided computational models of TMS and DBS neurostimulatory fields and conductance-based models of neurons exposed to stimulation. We demonstrated that tissues carry neurostimulation currents through frequency dependent resistive and capacitive properties not typically accounted for by past neurostimulation modeling work. We show that these fundamental brain tissue properties can have significant effects on the neurostimulatory-fields (capacitive and resistive current composition and spatial/temporal dynamics) and neural responses (stimulation threshold, ionic currents, and membrane dynamics). These findings highlight the importance of tissue impedance properties on neurostimulation and impact our understanding of the biological mechanisms and technological potential of neurostimulatory methods.

Movement-generated afference paired with transcranial magnetic stimulation: an associative stimulation paradigm.

BACKGROUND: A peripheral nerve stimulus can enhance or suppress the evoked response to transcranial magnetic stimulation (TMS) depending on the latency of the preceding peripheral nerve stimulation (PNS) pulse. Similarly, somatosensory afference from the passively moving limb can transiently alter corticomotor excitability, in a phase-dependent manner. The repeated association of PNS with TMS is known to modulate corticomotor excitability; however, it is unknown whether repeated passive-movement associative stimulation (MAS) has similar effects. METHODS: In a proof-of-principal study, using a cross-over design, seven healthy subjects received in separate sessions: (1) TMS (120% of the resting motor threshold-RMT, optimal site for Flexor Carpi Radialis) with muscle at rest; (2) TMS paired with cyclic passive movement during extension cyclic passive movement (400 pairs, 1 Hz), with the intervention order randomly assigned. Normality was tested using the Kolmogorov-Smirnov test, then compared to pre-intervention baseline using repeated measures ANOVA with a Dunnet multiple comparisons test. RESULTS: MAS led to a progressive and significant decrease in the motor evoked potential (MEP) amplitude over the intervention (R(2) = 0.6665, P < 0.0001), which was not evident with TMS alone (R(2) = 0.0068, P = 0.641). Post-intervention excitability reduction, only present with MAS intervention, remained for 20 min (0-10 min = 68.2 ± 4.9%, P < 0.05; 10-20 min = 73.3 ± 9.7%, P < 0.05). CONCLUSION: The association of somatosensory afference from the moving limb with TMS over primary motor cortex in healthy subjects can be used to modulate corticomotor excitability, and may have therapeutic implications.

An Experiment Using Functional Near-Infrared Spectroscopy and Robot-Assisted Multi-Joint Pointing Movements of the Lower Limb.

Stroke affects approximately 17 million individuals worldwide each year and is a leading cause of long-term disability. Robotic therapy has shown promise in helping stroke patients regain lost motor functions. One potential avenue for increasing the understanding of how motor recovery occurs is to study brain activation during the movements that are targeted by therapy in healthy individuals. Functional Near-Infrared Spectroscopy (fNIRS) has emerged as a promising neuroimaging technique for examining neural underpinnings of motor function. This study aimed to investigate fNIRS neural correlates of complex lower limb movements in healthy subjects. Participants were asked to perform cycles of rest and movement for 6 min using a robotic device for motor rehabilitation. The task required coordinated knee and ankle joint movements to point to targets displayed on a computer screen. Two experimental conditions with different levels of movement assistance provided by the robot were explored. The results showed that the fNIRS protocol effectively detected brain regions associated with motor control during the task. Notably, all subjects exhibited greater activation in the contralateral premotor area during the no-assistance condition compared to the assisted condition. In conclusion, fNIRS appears to be a valuable approach for detecting changes in oxyhemoglobin concentration associated with multi-joint pointing movements of the lower limb. This research might contribute to the understanding of stroke motor recovery mechanisms and might pave the way for improved rehabilitation treatments for stroke patients. However, further research is needed to fully elucidate the potential of fNIRS in studying motor function and its applications in clinical settings.

The evolution of Big Data in neuroscience and neurology.

Neurological diseases are on the rise worldwide, leading to increased healthcare costs and diminished quality of life in patients. In recent years, Big Data has started to transform the fields of Neuroscience and Neurology. Scientists and clinicians are collaborating in global alliances, combining diverse datasets on a massive scale, and solving complex computational problems that demand the utilization of increasingly powerful computational resources. This Big Data revolution is opening new avenues for developing innovative treatments for neurological diseases. Our paper surveys Big Data's impact on neurological patient care, as exemplified through work done in a comprehensive selection of areas, including Connectomics, Alzheimer's Disease, Stroke, Depression, Parkinson's Disease, Pain, and Addiction (e.g., Opioid Use Disorder). We present an overview of research and the methodologies utilizing Big Data in each area, as well as their current limitations and technical challenges. Despite the potential benefits, the full potential of Big Data in these fields currently remains unrealized. We close with recommendations for future research aimed at optimizing the use of Big Data in Neuroscience and Neurology for improved patient outcomes. Supplementary Information: The online version contains supplementary material available at 10.1186/s40537-023-00751-2.

Cost-Effectiveness Analysis to Inform Randomized Controlled Trial Design in Chronic Pain Research: Methods for Guiding Decisions on the Addition of a Run-In Period.

Introduction: Run-In (RI) periods can be used to improve the validity of randomized controlled trials (RCTs), but their utility in Chronic Pain (CP) RCTs is debated. Cost-effectiveness analysis (CEA) methods are commonly used in evaluating the results of RCTs, but they are seldom used for designing RCTs. We present a step-by-step overview to objectively design RCTs via CEA methods and specifically determine the cost effectiveness of a RI period in a CP RCT. Methods: We applied the CEA methodology to data obtained from several noninvasive brain stimulation CP RCTs, specifically focusing on (1) defining the CEA research question, (2) identifying RCT phases and cost ingredients, (3) discounting, (4) modeling the stochastic nature of the RCT, and (5) performing sensitivity analyses. We assessed the average cost-effectiveness ratios and incremental cost effectiveness ratios of varied RCT designs and the impact on cost-effectiveness by the inclusion of a RI period vs. No-Run-In (NRI) period. Results: We demonstrated the potential impact of varying the number of institutions, number of patients that could be accommodated per institution, cost and effectiveness discounts, RCT component costs, and patient adherence characteristics on varied RI and NRI RCT designs. In the specific CP RCT designs that we analyzed, we demonstrated that lower patient adherence, lower baseline assessment costs, and higher treatment costs all necessitated the inclusion of an RI period to be cost-effective compared to NRI RCT designs. Conclusions: Clinical trialists can optimize CP RCT study designs and make informed decisions regarding RI period inclusion/exclusion via CEA methods.

Effect of gravity on robot-assisted motor training after chronic stroke: a randomized trial.

OBJECTIVES: To determine the efficacy of 2 distinct 6-week robot-assisted reaching programs compared with an intensive conventional arm exercise program (ICAE) for chronic, stroke-related upper-extremity (UE) impairment. To examine whether the addition of robot-assisted training out of the horizontal plane leads to improved outcomes. DESIGN: Randomized controlled trial, single-blinded, with 12-week follow-up. SETTING: Research setting in a large medical center. PARTICIPANTS: Adults (N=62) with chronic, stroke-related arm weakness stratified by impairment severity using baseline UE motor assessments. INTERVENTIONS: Sixty minutes, 3 times a week for 6 weeks of robot-assisted planar reaching (gravity compensated), combined planar with vertical robot-assisted reaching, or intensive conventional arm exercise program. MAIN OUTCOME MEASURE: UE Fugl-Meyer Assessment (FMA) mean change from baseline to final training. RESULTS: All groups showed modest gains in the FMA from baseline to final with no significant between group differences. Most change occurred in the planar robot group (mean change ± SD, 2.94 ± 0.77; 95% confidence interval [CI], 1.40-4.47). Participants with greater motor impairment (n=41) demonstrated a larger difference in response (mean change ± SD, 2.29 ± 0.72; 95% CI, 0.85-3.72) for planar robot-assisted exercise compared with the intensive conventional arm exercise program (mean change ± SD, 0.43 ± 0.72; 95% CI, -1.00 to 1.86). CONCLUSIONS: Chronic UE deficits because of stroke are responsive to intensive motor task training. However, training outside the horizontal plane in a gravity present environment using a combination of vertical with planar robots was not superior to training with the planar robot alone.

A minimally invasive endoscope assisted retrosigmoid approach for removal of arachnoid cysts in the internal auditory canal: a step by step description.

INTRODUCTION: Arachnoid cyst in the internal auditory canal is a quite rare pathology but due to its compressive action on the nerves in this district should be surgically removed. Several surgical techniques have been proposed but no surgeons have used the minimally assisted endoscope retrosigmoid approach for its removal. OBJECTIVE: To investigate the feasibility of using a minimally invasive endoscope assisted retro-sigmoid approach for surgical removal of arachnoid cysts in the internal auditory canal. METHODS: Minimally invasive endoscope assisted retrosigmoid approach allows to access to the internal auditory canal through a minimally invasive retrosigmoid approach that combines the use of a microscope and an endoscope. It is performed in six steps: soft tissue step, bone step, dura step, cerebellopontine angle step (performed using an endoscope and a microscope), microscope-endoscope assisted arachnoid cysts removal and closure. We tested minimally invasive endoscope assisted retrosigmoid approach for removal of arachnoid cysts in the internal auditory canal on two human cadaveric heads (specimens) of subjects affected from audio-vestibular disorders and with arachnoid cysts in the internal auditory canal confirmed by magnetic resonance imaging. RESULTS: The mass was completely and successfully removed from the two specimens with no damage to the nerves and/or vessels in the surgical area. CONCLUSION: The results of our study are encouraging and support the feasibility of using minimally invasive endoscope assisted retrosigmoid approach for removal of arachnoid cysts in the internal auditory canal. While further clinical in-vivo studies are needed to confirm the accuracy and safety of using the minimally invasive endoscope assisted retrosigmoid approach for this specific surgery, our group has successfully used the minimally invasive endoscope assisted retrosigmoid approach in the treatment of microvascular compressive syndrome, schwannoma removal and vestibular nerve resection.

Arachnoid Cysts of the Internal Auditory Canal: Multiplanar Magnetic Resonance Imaging With Audio-Vestibular Correlates.

OBJECTIVES/HYPOTHESIS: To investigate prevalence, radiological characteristics, and functional correlates of arachnoid cysts (AC) of the internal auditory canal (IAC) region, including associations of nerve compression with auditory/vestibular symptoms and asymmetrical audiogram or vestibular testing. STUDY DESIGN: Retrospective study. METHODS: T2-weighted magnetic resonance imaging (MRI) studies of IACs were retrospectively analyzed from 1247 patients with asymmetric auditory or vestibular symptoms. Patients with radiological findings of AC of the IAC were identified. Multiplanar analysis was used to analyze cyst position in the IAC and assess nerve displacement or compression. Size, position, and presence of nerve compression were correlated with symptoms. RESULTS: Twenty-four patients had a cyst in the middle or fundus in the IAC. Diameter (P = .04) and position (P = .002) of AC were associated with symptoms. Sagittal analyses identified displacement versus compression (P = .003) more reliably than axial imaging. Symptom laterality was associated with the site of radiological abnormality. Vestibular nerve compression was associated with vertigo (P = .0001), and cochlear nerve compression was associated with auditory symptoms (P < .0001). CONCLUSIONS: In a retrospective series of patients undergoing MRI of IACs for asymmetric auditory or vestibular impairment, clinical symptom profile correlated with blinded assessment of IAC lesions. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2323-2331, 2021.

ENT-MS-12 questionnaire: A novel tool to investigate otolaryngology symptoms in patients with relapsing-remitting multiple sclerosis. Results from a pilot study.

BACKGROUND: Multiple sclerosis (MS) is associated with otolaryngology-related manifestations including vestibular or auditory symptoms; facial motor or sensory disorders; voice or swallowing impairment; and snoring/sleep apnea. Because these symptoms are nonspecific, their significance in MS is seldom recognized by patients with MS and their physicians; yet, presence of these symptoms may be a harbinger of impending relapse or disease progression. We developed and investigated a survey instrument, the ENT-MS-12, to standardize reporting of otolaryngology symptoms in patients with MS, correlating its scoring with disability and lesions. METHODS: The ENT-MS-12 was administered to 40 patients with relapsing-remitting MS in different phases of their disease. We collected data using the Expanded Disability Status Scale (EDSS) and analyzed patient brain MRIs to evaluate the state (active or non-active) of brain lesions based on gadolinium enhancement. Odds ratios for diverse otolaryngology symptoms across the EDSS scores and brain lesions were calculated. RESULTS: Higher EDSS scores were associated with auditory and vestibular symptoms (Odd Ratio (OR): 3.06; p: 0.0003); voice and swallowing symptoms (OR: 6.8; p=0.007); and snoring/sleep apnea (OR: 5.1; p=0.03). Presence of active brain lesions was also associated with auditory and vestibular symptoms (OR: 6.7); voice and swallowing symptoms (OR: 5.7); and snoring/sleep apnea (OR: 5). CONCLUSIONS: The ENT-MS-12 survey instrument standardizes reporting of otolaryngology symptoms in patients with MS and documents association between symptoms and phase of disease in this series. Because ear, nose and throat (ENT)- related symptoms (i.e., sensory symptoms, such as numbness) are under-reported in MS, further investigation is warranted, as such data may improve clinical management of MS.

Accurate prediction of clinical stroke scales and improved biomarkers of motor impairment from robotic measurements.

OBJECTIVE: One of the greatest challenges in clinical trial design is dealing with the subjectivity and variability introduced by human raters when measuring clinical end-points. We hypothesized that robotic measures that capture the kinematics of human movements collected longitudinally in patients after stroke would bear a significant relationship to the ordinal clinical scales and potentially lead to the development of more sensitive motor biomarkers that could improve the efficiency and cost of clinical trials. MATERIALS AND METHODS: We used clinical scales and a robotic assay to measure arm movement in 208 patients 7, 14, 21, 30 and 90 days after acute ischemic stroke at two separate clinical sites. The robots are low impedance and low friction interactive devices that precisely measure speed, position and force, so that even a hemiparetic patient can generate a complete measurement profile. These profiles were used to develop predictive models of the clinical assessments employing a combination of artificial ant colonies and neural network ensembles. RESULTS: The resulting models replicated commonly used clinical scales to a cross-validated R2 of 0.73, 0.75, 0.63 and 0.60 for the Fugl-Meyer, Motor Power, NIH stroke and modified Rankin scales, respectively. Moreover, when suitably scaled and combined, the robotic measures demonstrated a significant increase in effect size from day 7 to 90 over historical data (1.47 versus 0.67). DISCUSSION AND CONCLUSION: These results suggest that it is possible to derive surrogate biomarkers that can significantly reduce the sample size required to power future stroke clinical trials.

Pain perception in chronic knee osteoarthritis with varying levels of pain inhibitory control: an exploratory study.

Background and aims Pain is a disabling symptom in knee osteoarthritis (KOA) and its underlying mechanism remains poorly understood. Dysfunction of descending pain modulatory pathways and reduced pain inhibition enhance pain facilitation in many chronic pain syndromes but do not fully explain pain levels in chronic musculoskeletal conditions. The objective of this study is to explore the association of clinical variables with pain intensity perception in KOA individuals with varying levels of Conditioned Pain Modulation (CPM) response. Methods This is a cross-sectional, exploratory analysis using baseline data of a randomized clinical trial investigating the effects of a non-invasive brain stimulation treatment on the perception of pain and functional limitations due to KOA. Sixty-three subjects with KOA were included in this study. Data on pain perception, mood perception, self-reported depression, physical function, quality of life, and quantitative sensory testing was collected. Multiple linear regression analysis was performed to explore the association between the clinical variables with pain perception for individuals with different levels of CPM response. Results For KOA patients with limited CPM response, perception of limitations at work/other activities due to emotional problems and stress scores were statistically significantly associated with pain scores, F(2, 37) = 7.02, p < 0.01. R-squared = 0.275. For KOA patients with normal CPM response, general health perception scores were statistically significantly associated with pain scores, F(1, 21) = 5.60, p < 0.05. R-squared = 0.2104. Limitations of this study include methodology details, small sample size and study design characteristics. Conclusions Pain intensity perception is associated differently with clinical variables according to the individual CPM response. Mechanistic models to explain pain perception in these two subgroups of KOA subjects are discussed.

A Novel Bone Conduction Hearing System May Improve Memory Function in Children with Single Side Hearing loss: A Case-Control Study.

OBJECTIVES: To evaluate the effects of an adhesive adapter prosthesis (AAP) on memory function in pediatric subjects with single side hearing loss (SSHL). MATERIALS AND METHODS: Case-control study. 19 pediatric subjects with mild to moderate SSHL treated with AAP and 15 subjects with normal hearing (control group) were included in this study. Working and short-term memory functions were tested in all subjects, in silence and noise conditions. In SSHL subjects, tests were performed before the AAP was applied (T0) and at 1-month (T1) follow-up. The control group was tested once. RESULTS: AAP significantly improved working memory function in noise as measured at T1 (p<0.01) compared with T0, but T1 scores in children with SSHL remained significantly different from the ones of the control group (p<0.01). AAP also significantly improved short- term memory function test scores at T1 compared with T0 (p<0.01), but despite being in the normal range for the subjects' age, the scores remained significantly different from those of the control group (p<0.01). CONCLUSION: In pediatric subjects with mild, moderate, and moderate-severe SSHL, restoration of bilateral hearing through AAP improved short-term memory function and working memory function in noise, as measured at 1 month follow-up; however, AAP did not seem to lead to a full restoration of such functions as measured by a comparison with healthy controls. Further studies with longer follow-ups might help elucidate whether AAP can elicit further improvements in memory functions.