Gaussian Processes for Hearing Threshold Estimation Using Auditory Brainstem Responses.

The Auditory Brainstem Response (ABR) plays an important role in diagnosing and managing hearing loss, but can be challenging and time-consuming to measure. Test times are especially long when multiple ABR measurements are needed, e.g., when estimating hearing threshold at a range of frequencies. While many detection methods have been developed to reduce ABR test times, the majority were designed to detect the ABR at a single stimulus level and do not consider correlations in ABR waveforms across levels. These correlations hold valuable information, and can be exploited for more efficient hearing threshold estimation. This was achieved in the current work using a Gaussian Process (GP), i.e., a Bayesian approach for non-linear regression. The function to estimate with the GP was the ABR's amplitude across stimulus levels, from which hearing threshold was ultimately inferred. Active learning rules were also designed to automatically adjust the stimulus level and efficiently locate hearing threshold. Simulation results show test time reductions of up to  âˆ¼ 50% for the GP compared to a sequentially applied Hotelling's T2 test, which does not consider correlations across ABR waveforms. A case study was also included to briefly assess the GP approach in ABR data from an adult volunteer.

Unstable dimension variability and heterodimensional cycles in the border-collision normal form.

Chaotic attractors commonly contain periodic solutions with unstable manifolds of different dimensions. This allows for a zoo of dynamical phenomena not possible for hyperbolic attractors. The purpose of this Letter is to emphasize the existence of these phenomena in the border-collision normal form. This is a continuous, piecewise-linear family of maps that is physically relevant as it captures the dynamics created in border-collision bifurcations in diverse applications. Since the maps are piecewise linear, they are relatively amenable to an exact analysis. We explicitly identify parameter values for heterodimensional cycles and argue that the existence of heterodimensional cycles between two given saddles can be dense in parameter space. We numerically identify key bifurcations associated with unstable dimension variability by studying a one-parameter subfamily that transitions continuously from where periodic solutions are all saddles to where they are all repellers. This is facilitated by fast and accurate computations of periodic solutions; indeed the piecewise-linear form should provide a useful testbed for further study.

Pattern Formation in a Spatially Extended Model of Pacemaker Dynamics in Smooth Muscle Cells.

Spatiotemporal patterns are common in biological systems. For electrically coupled cells, previous studies of pattern formation have mainly used applied current as the primary bifurcation parameter. The purpose of this paper is to show that applied current is not needed to generate spatiotemporal patterns for smooth muscle cells. The patterns can be generated solely by external mechanical stimulation (transmural pressure). To do this we study a reaction-diffusion system involving the Morris-Lecar equations and observe a wide range of spatiotemporal patterns for different values of the model parameters. Some aspects of these patterns are explained via a bifurcation analysis of the system without coupling - in particular Type I and Type II excitability both occur. We show the patterns are not due to a Turing instability and that the spatially extended model exhibits spatiotemporal chaos. We also use travelling wave coordinates to analyse travelling waves.

Autologous skin-derived neural precursor cell therapy reverses canine Alzheimer dementia-like syndrome in a proof of concept veterinary trial.

BACKGROUND: Older companion dogs naturally develop a dementia-like syndrome with biological, clinical and therapeutic similarities to Alzheimer disease (AD). Given there has been no new safe, clinically effective and widely accessible treatment for AD for almost 20 years, an all-new cell therapeutic approach was trialled in canine veterinary patients, and further modelled in aged rats for more detailed neurobiological analysis. METHODS: A Phase 1/2A veterinary trial was conducted in N = 6 older companion dogs with definitive diagnosis of Canine Cognitive Dysfunction (CCD). Treatment comprised direct microinjection of 250,000 autologous skin-derived neuroprecursors (SKNs) into the bilateral hippocampus using MRI-guided stereotaxis. Safety was assessed clinically and efficacy using the validated Canine Cognitive Dysfunction Rating Scale (CCDR) at baseline and 3-month post treatment. Intention to treat analysis imputed a single patient that had a surgical adverse event requiring euthanasia. Three dog brains were donated following natural death and histology carried out to quantify Alzheimer pathology as well as immature neurons and synapses; these were compared to a brain bank (N = 12) of untreated aged dogs with and without CCD. Further, an age-related memory dysfunction rat model (N = 16) was used to more closely evaluate intrahippocampal engraftment of canine SKN cells, focusing on mnemonic and synaptic effects as well as donor cell survival, neurodifferentation and electrophysiologic circuit integration in a live hippocampal slice preparation. RESULTS: Four out-of-five dogs improved on the primary clinical CCDR endpoint, three fell below diagnostic threshold, and remarkably, two underwent full syndromal reversal lasting up to 2 years. At post mortem, synaptic density in the hippocampus specifically was nine standard deviations above non-treated dogs, and intensity of new neurons also several fold higher. There was no impact on AD pathology or long-term safety signals. Modelling in aged rats replicated the main canine trial findings: hippocampally-dependent place memory deficits were reversed and synaptic depletion rescued. In addition, this model confirmed donor cell survival and migration throughout the hippocampus, neuronal differentiation in situ, and physiologically-correct integration into pyramidal layer circuits. CONCLUSIONS: With further development, SKN cell therapy may have potential for treating carefully chosen AD patients based on neurosynaptic restoration in the hippocampus.

Robust Devaney chaos in the two-dimensional border-collision normal form.

The collection of all non-degenerate, continuous, two-piece, piecewise-linear maps on R2 can be reduced to a four-parameter family known as the two-dimensional border-collision normal form. We prove that throughout an open region of parameter space, this family has an attractor satisfying Devaney's definition of chaos. This strengthens the existing results on the robustness of chaos in piecewise-linear maps. We further show that the stable manifold of a saddle fixed point, despite being a one-dimensional object, densely fills an open region containing the attractor. Finally, we identify a heteroclinic bifurcation, not described previously, at which the attractor undergoes a crisis and may be destroyed.

Controlling test specificity for auditory evoked response detection using a frequency domain bootstrap.

BACKGROUND: Statistical detection methods are routinely used to automate auditory evoked response (AER) detection and assist clinicians with AER measurements. However, many of these methods are built around statistical assumptions that can be violated for AER data, potentially resulting in reduced or unpredictable test performances. This study explores a frequency domain bootstrap (FDB) and some FDB modifications to preserve test performance in serially correlated non-stationary data. METHOD: The FDB aims to generate many surrogate recordings, all with similar serial correlation as the original recording being analysed. Analysing the surrogates with the detection method then gives a distribution of values that can be used for inference. A potential limitation of the conventional FDB is the assumption of stationary data with a smooth power spectral density (PSD) function, which is addressed through two modifications. COMPARISONS WITH EXISTING METHODS: The FDB was compared to a conventional parametric approach and two modified FDB approaches that aim to account for heteroskedasticity and non-smooth PSD functions. Hotelling's T2(HT2) test applied to auditory brainstem responses was the test case. RESULTS: When using conventional HT2, false-positive rates deviated significantly from the nominal alpha-levels due to serial correlation. The false-positive rates of the modified FDB were consistently closer to the nominal alpha-levels, especially when data was strongly heteroskedastic or the underlying PSD function was not smooth due to e.g. power lines noise. CONCLUSION: The FDB and its modifications provide accurate, recording-dependent approximations of null distributions, and an improved control of false-positive rates relative to parametric inference for auditory brainstem response detection.

An unusual presentation of dysarthria in a young patient, a stroke mimic.

Internal carotid artery dissection commonly affects younger patients. We present a case of a previously fit and well 43-year-old gentleman who presented with a sudden onset of slurring of speech, with right-sided tongue deviation and fasciculation on examination. Signs and symptoms began following participation in a home workout class. Magnetic resonance angiography revealed right-sided extracrainal internal carotid artery dissection leading to right-sided unilateral twelfth cranial nerve palsy.

The presence, morphology and clinical significance of vertebral body malformations in an Australian population of French Bulldogs and Pugs.

OBJECTIVE: To describe the incidence, morphology and clinical significance of congenital vertebral malformations (CVM) in two breeds of brachycephalic dogs presenting to a referral veterinary hospital. DESIGN: Prospective cohort study series. MATERIALS AND METHODS: Forty-nine French Bulldogs and Pugs were prospectively evaluated and placed in one of two groups based on whether or not they presented for neurological signs referable to spinal cord disease. A computed tomography (CT) of their entire spine was obtained and the presence and classification of CVM along with the degree of spinal kyphosis recorded for all dogs. Statistical analysis was performed to identify clinical associations between these factors (P < 0.05). RESULTS: CVM were prevalent across both breeds with the French Bulldog having more malformations than the Pug (Kruskal-Wallis nonparametric analysis of variance, P < 0.0001). Breed associated vertebral malformation subtypes included butterfly subtype in French Bulldogs (Chi-square, P = 0.0002), and transitional subtype in Pugs (odds ratio, 22.7; P = 0.000). A new subtype, dorsal wedge, was observed in 12 cases. The presence, number and subtype of vertebral malformation were not reliable for predicting the development of neurological signs across both breeds (Chi-square, P > 0.05). However, spinal kyphosis >35° calculated via Cobb angle was associated with Pugs that had neurological deficits (Chi-square, P = 0.028). CONCLUSIONS: Congenital vertebral malformations largely appear to be incidental findings in this population of French Bulldogs but are of more significance in the Pug breed when spinal kyphosis is >35°. French Bulldogs that have spinal cord disease and CVM are more likely to have pathology distant to CVM with intervertebral disc herniation most common.

Streamlined variational inference for higher level group-specific curve models.

A two-level group-specific curve model is such that the mean response of each member of a group is a separate smooth function of a predictor of interest. The three-level extension is such that one grouping variable is nested within another one, and higher level extensions are analogous. Streamlined variational inference for higher level group-specific curve models is a challenging problem. We confront it by systematically working through two-level and then three-level cases and making use of the higher level sparse matrix infrastructure laid down in Nolan and Wand (2019). A motivation is analysis of data from ultrasound technology for which three-level group-specific curve models are appropriate. Whilst extension to the number of levels exceeding three is not covered explicitly, the pattern established by our systematic approach sheds light on what is required for even higher level group-specific curve models.

Correlation between biochemical features and outcomes of preoperative imaging (SPECT-CT and Ultrasound) in primary hyperparathyroidism.

Background: Primary hyperparathyroidism is the third most common endocrine disorder, diagnosed by elevated parathyroid hormone (PTH) in hypercalcaemia. Several biochemical factors have been described to suggest severity of disease and may be correlated with preoperative imaging. Methods: This was a retrospective study of patients who underwent parathyroidectomy over a 3-year period. Preoperative calcium, PTH, vitamin D levels, ALP (alkaline phosphatase), vitamin D, serum phosphate and US and SPECT-CT positivity was noted. Results: 176 patients underwent parathyroidectomy and these were divided into 4 groups based on preoperative calcium. Overall, 61% of patients showed concordance between imaging and operative findings. Severe hypercalcaemia was associated with higher PTH levels, lower vitamin D levels, an increased rate of abnormal ALP levels, lower phosphate, male gender and highest rate of imaging concordance. Imaging positivity was associated with severe hypercalcaemia and elevated PTH levels. Level of PTH >125 pmol/L and hypercalcaemia >2.8 mmol/L are the most accurate cut-off levels for scan positivity. Conclusion: Biochemical factors associated with severity of the disease are directly correlated with positivity of preoperative imaging while ALP and vitamin D did not influence the preoperative imaging positivity but are associated with disease adversity. Serum phosphate level independently predicted results of parathyroid US.

Numerical Bifurcation Analysis of Pacemaker Dynamics in a Model of Smooth Muscle Cells.

Evidence from experimental studies shows that oscillations due to electro-mechanical coupling can be generated spontaneously in smooth muscle cells. Such cellular dynamics are known as pacemaker dynamics. In this article, we address pacemaker dynamics associated with the interaction of [Formula: see text] and [Formula: see text] fluxes in the cell membrane of a smooth muscle cell. First we reduce a pacemaker model to a two-dimensional system equivalent to the reduced Morris-Lecar model and then perform a detailed numerical bifurcation analysis of the reduced model. Existing bifurcation analyses of the Morris-Lecar model concentrate on external applied current, whereas we focus on parameters that model the response of the cell to changes in transmural pressure. We reveal a transition between Type I and Type II excitabilities with no external current required. We also compute a two-parameter bifurcation diagram and show how the transition is explained by the bifurcation structure.

Retrospective analysis of 736 cases of canine gastric dilatation volvulus.

OBJECTIVE: To identify factors influencing the survival of confirmed gastric dilatation volvulus (GDV) cases presented to a specialist referral and emergency hospital. METHODS: Clinical records of confirmed GDV cases admitted to two specialist referral and emergency centres in Sydney (Animal Referral Hospital (ARH) Homebush and ARH Baulkham Hills) between July 1999 and July 2019 were searched. RESULTS: A total of 736 GDV cases were reviewed, of which 460 dogs were surgically treated and 276 dogs were humanely killed. The survival rates of patients operated on by general surgeons and specialists were 81.7% and 88.7%, respectively. Both incisional gastropexy and belt-loop gastropexy were clinically effective in treating GDV, with no significant difference in survival rates. Intraoperative mortality rates for general surgeons and specialists were 7.0% and 2.9%, respectively. The odds of mortality in dogs operated on by general surgeons were 2.03 times those operated on by specialist surgeons. The odds of mortality in dogs presented between 3:00 and 9:00 am were 3.57 times those of dogs presented between 9:00 am and 9:00 pm. The odds of mortality in dogs where the duration from presentation to completion of surgery was more than 3 h were 2.53 times those of dogs where time lapsed was equal or less than 3 h. CONCLUSION: The results suggested that admission time was statistically significantly related to the survival rate. Dogs operated on by specialist surgeons had a significantly higher survival rate compared to those operated on by general surgeons. Clinicians should aim to stabilise and complete surgical correction of GDV as soon as possible to decrease the mortality.

A group sequential test for ABR detection.

Objective: To detect the auditory brainstem response (ABR) automatically using an innovative sequentially applied Hotelling's T 2 test, with the overall goal of optimising test time whilst controlling the false-positive rate (FPR). Design: The stage-wise critical decision boundaries for accepting or rejecting the null hypothesis were found using a new approach called the Convolutional Group Sequential Test (CGST). Specificity, sensitivity, and test time were evaluated using simulations and subject recorded data. Study sample: Data consists of click-evoked ABR threshold series from 12 normal hearing adults, and recordings of EEG background activity from 17 normal hearing adults. Results: Reductions in mean test time of up to 40-45% were observed for the sequential test, relative to a conventional "single shot" test where the statistical test is applied to the data just once. To obtain these results, it will occasionally be necessary to run the test to a higher number of stimuli, i.e. the maximum test time needs to be increased. Conclusions: The CGST can be used to control the specificity of a sequentially applied ABR detection method. Doing so can reduce test time, relative to the "single shot" test, when considered across a cohort of test subjects.

Microscopic Imaging of the Stress Tensor in Diamond Using in Situ Quantum Sensors.

The precise measurement of mechanical stress at the nanoscale is of fundamental and technological importance. In principle, all six independent variables of the stress tensor, which describe the direction and magnitude of compression/tension and shear stress in a solid, can be exploited to tune or enhance the properties of materials and devices. However, existing techniques to probe the local stress are generally incapable of measuring the entire stress tensor. Here, we make use of an ensemble of atomic-sized in situ strain sensors in diamond (nitrogen-vacancy defects) to achieve spatial mapping of the full stress tensor, with a submicrometer spatial resolution and a sensitivity of the order of 1 MPa (10 MPa) for the shear (axial) stress components. To illustrate the effectiveness and versatility of the technique, we apply it to a broad range of experimental situations, including mapping the stress induced by localized implantation damage, nanoindents, and scratches. In addition, we observe surprisingly large stress contributions from functional electronic devices fabricated on the diamond and also demonstrate sensitivity to deformations of materials in contact with the diamond. Our technique could enable in situ measurements of the mechanical response of diamond nanostructures under various stimuli, with potential applications in strain engineering for diamond-based quantum technologies and in nanomechanical sensing for on-chip mass spectroscopy.

Mapping the contact area of the patellofemoral joint: the relationship between stability and joint congruence.

AIMS: The aim of this study was to determine and compare the congruency of the articular surface contact area of the patellofemoral joint (PFJ) during both active and passive movement of the knee with the use of an MRI mapping technique in both the stable and unstable PFJ. PATIENTS AND METHODS: A prospective case-control MRI imaging study of patients with a history of PFJ instability and a control group of volunteers without knee symptoms was performed. The PFJs were imaged with the use of an MRI scan during both passive and active movement from 0° through to 40° of flexion. The congruency through measurement of the contact surface area was mapped in 5-mm intervals on axial slices. In all, 40 patients were studied. The case group included 31 patients with symptomatic patellofemoral instability and the control group of nine asymptomatic volunteers. The ages were well matched between the case and control groups. The mean age was 25 years (16 to 42; sd 6.9) in the case group and 26 years (19 to 32; sd 5.1) in the control group. There were 19 female and 12 male patients in the case group. RESULTS: The unstable PFJs were demonstrably less congruent than the stable PFJs throughout the range of knee movement. The greatest mean differences in congruency between unstable and stable PFJ's were observed between 11° and 20° flexion (1.73 cm2vs 4.00 cm2; p < 0.005). CONCLUSION: The unstable PFJ is less congruent than the stable PFJ throughout the range of knee movement studied. This approach to mapping PFJ congruency produces a measurable outcome and will allow the assessment of pre- and postoperative results following surgical intervention. This may facilitate the design of new procedures for patients with PFJ instability. If a single axial series is to be obtained on MRI scan, the authors recommend 11° to 20° of tibiofemoral flexion, as this was shown to have the greatest difference in contact surface area between the case and control groups. Cite this article: Bone Joint J 2019;101-B:552-558.

Mirror therapy and treadmill training for patients with chronic stroke: a pilot randomized controlled trial.

BACKGROUND: Previous lower-limb mirror therapy research has focused on non-weight bearing interventions. OBJECTIVES: The primary aim of this study was to investigate the effect and feasibility of a combination of mirror therapy and treadmill training on post-stroke lower-limb recovery compared to a placebo intervention. METHODS: All patients (N = 30) walked on a treadmill for 30 min per day, 3 days per week, for 4 weeks. The mirror therapy and treadmill training group (n = 15) walked on the treadmill while viewing a reflection of their non-paretic limb in a mirror positioned in their mid-sagittal plane. The placebo group (n = 15) received no mirror visual feedback due to an altered mirror position. PRIMARY OUTCOME MEASURES: Ten Metre Walk Test (10MWT) and Six Minute Walk Test (6MWT). SECONDARY OUTCOME MEASURES: Modified Ashworth Scale (MAS) and Fugl-Meyer Assessment-Lower Extremity (FMA-LE). Feasibility was appraised by examining participant compliance and any adverse events. RESULTS: No significant between group differences were demonstrated for the 10MWT, 6MWT or FMA-LE at post-training or 3-month follow-up assessment. A significant between group difference on the MAS was demonstrated in the reduction of ankle dorsiflexion muscle tone (p = 0.006) and ankle plantarflexion muscle tone (p = 0.01) in the mirror therapy group compared to the placebo group at post-training assessment but not at 3-month follow-up. CONCLUSION: Our study reveals that in our group of patients with chronic stroke, mirror therapy combined with treadmill training facilitated significant reductions in ankle muscle tone (p < 0.05) compared to a placebo intervention.

Measuring depth of anaesthesia using changes in directional connectivity: a comparison with auditory middle latency response and estimated bispectral index during propofol anaesthesia.

General anaesthesia is associated with changes in connectivity between different regions of the brain, the assessment of which has the potential to provide a novel marker of anaesthetic effect. We propose an index that quantifies the strength and direction of information flow in electroencephalographic signals collected across the scalp, assess its performance in discriminating 'wakefulness' from 'anaesthesia', and compare it with estimated bispectral index and the auditory middle latency response. We used a step-wise slow induction of anaesthesia in 10 patients to assess graded changes in electroencephalographic directional connectivity at propofol effect-site concentrations of 2 µg.ml-1 , 3 µg.ml-1 and 4 µg.ml-1 . For each stable effect-site concentration, connectivity was estimated from multichannel electroencephalograms using directed coherence, together with middle latency response and estimated bispectral index. We used a linear support vector machine classifier to compare the performance of the different electroencephalographic features in discriminating wakefulness from anaesthesia. We found a significant reduction in the strength of long-range connectivity (interelectrode distance > 10 cm) (p < 0.008), and a reversal of information flow from markedly postero-frontal to fronto-posterior (p < 0.006) between wakefulness and a propofol effect-site concentration of 2 µg.ml-1 . This then remained relatively constant as effect-site concentration increased, consistent with a step change in directed coherence with anaesthesia. This contrasted with the gradual change with increasing anaesthetic dose observed for estimated bispectral index and middle latency response. Directed coherence performed best in discriminating wakefulness from anaesthesia with an accuracy of 95%, indicating the potential of this new method (on its own or combined with others) for monitoring adequacy of anaesthesia.

Cerebrospinal Fluid Ceruloplasmin, Haptoglobin, and Vascular Endothelial Growth Factor Are Associated with Neurocognitive Impairment in Adults with HIV Infection.

Dysregulated iron transport and a compromised blood-brain barrier are implicated in HIV-associated neurocognitive disorders (HAND). We quantified the levels of proteins involved in iron transport and/or angiogenesis-ceruloplasmin, haptoglobin, and vascular endothelial growth factor (VEGF)-as well as biomarkers of neuroinflammation, in cerebrospinal fluid (CSF) from 405 individuals with HIV infection and comprehensive neuropsychiatric assessments. Associations with HAND [defined by a Global Deficit Score (GDS) ≥ 0.5, GDS as a continuous measure (cGDS), or by Frascati criteria] were evaluated for the highest versus lowest tertile of each biomarker, adjusting for potential confounders. Higher CSF VEGF was associated with GDS-defined impairment [odds ratio (OR) 2.17, p = 0.006] and cGDS in unadjusted analyses and remained associated with GDS impairment after adjustment (p = 0.018). GDS impairment was also associated with higher CSF ceruloplasmin (p = 0.047) and with higher ceruloplasmin and haptoglobin in persons with minimal comorbidities (ORs 2.37 and 2.13, respectively; both p = 0.043). In persons with minimal comorbidities, higher ceruloplasmin and haptoglobin were associated with HAND by Frascati criteria (both p < 0.05), and higher ceruloplasmin predicted worse impairment (higher cGDS values, p < 0.01). In the subgroup with undetectable viral load and minimal comorbidity, CSF ceruloplasmin and haptoglobin were strongly associated with GDS impairment (ORs 5.57 and 2.96, respectively; both p < 0.01) and HAND (both p < 0.01). Concurrently measured CSF IL-6 and TNF-α were only weakly correlated to these three biomarkers. Higher CSF ceruloplasmin, haptoglobin, and VEGF are associated with a significantly greater likelihood of HAND, suggesting that interventions aimed at disordered iron transport and angiogenesis may be beneficial in this disorder.

A general framework for boundary equilibrium bifurcations of Filippov systems.

As parameters are varied, a boundary equilibrium bifurcation (BEB) occurs when an equilibrium collides with a discontinuity surface in a piecewise-smooth system of ordinary differential equations. Under certain genericity conditions, at a BEB, the equilibrium either transitions to a pseudo-equilibrium (on the discontinuity surface) or collides and annihilates with a coexisting pseudo-equilibrium. These two scenarios are distinguished by the sign of a certain inner product. Here, it is shown that this sign can be determined from the number of unstable directions associated with the two equilibria by using techniques developed by Feigin. A normal form is proposed for BEBs in systems of any number of dimensions. The normal form involves a companion matrix, as does the leading order sliding dynamics, and so the connection to the stability of the equilibria is explicit. In two dimensions, the parameters of the normal form distinguish, in a simple way, the eight topologically distinct cases for the generic local dynamics at a BEB. A numerical exploration in three dimensions reveals that BEBs can create multiple attractors and chaotic attractors and that the equilibrium at the BEB can be unstable even if both equilibria are stable. The developments presented here stem from seemingly unutilised similarities between BEBs in discontinuous systems (specifically Filippov systems as studied here) and BEBs in continuous systems for which analogous results are, to date, more advanced.

Mirror therapy for improving lower limb motor function and mobility after stroke: A systematic review and meta-analysis.

BACKGROUND: Mirror therapy has been proposed as an effective intervention for lower limb rehabilitation post stroke. RESEARCH QUESTION: This systematic review with meta-analysis examined if lower limb mirror therapy improved the primary outcome measures of muscle tone and motor function and the secondary outcome measures balance characteristics, functional ambulation, walking velocity, passive range of motion (PROM) for ankle dorsiflexion and gait characteristics in patients with stroke compared to other interventions. METHODS: Standardised mean differences (SMD) and mean differences (MD) were used to assess the effect of mirror therapy on lower limb functioning. RESULTS: Nine studies were included in the review. Among the primary outcome measures there was evidence of a significant effect of mirror therapy on motor function compared with sham and non-sham interventions (SMD 0.54; 95% CI 0.24-0.93). Furthermore, among the secondary outcome measures there was evidence of a significant effect of mirror therapy for balance capacity (SMD -0.55; 95% CI -1.01 to -0.10), walking velocity (SMD 0.71; 95% CI 0.35-1.07), PROM for ankle dorsiflexion (SMD 1.20; 95% CI 0.71-1.69) and step length (SMD 0.56; 95% CI -0.00 to 1.12). SIGNIFICANCE: The results indicate that using mirror therapy for the treatment of certain lower limb deficits in patients with stroke may have a positive effect. Although results are somewhat positive, overly favourable interpretation is cautioned due to methodological issues concerning included studies.