Sensory Symptoms without Structural Pathology in Patients with Gluten Sensitivity.

We report on a group of patients with gluten sensitivity with and without coeliac disease presenting with unexplained sensory symptoms in the absence of structural pathology. METHODS: The patients were selected from the gluten neurology clinic based at the Royal Hallamshire Hospital, Sheffield, UK, on the basis of sensory symptoms but normal neuroaxis imaging and peripheral nerve evaluation. RESULTS: A total of 30 patients were identified with a mean age at presentation of 47 years. The prevalence of enteropathy was 78%. The sensory disturbance was characterised by tingling at 50%, numbness at 27%, pain at 20%, burning at 13% and "buzzing" feeling at 7%. The distribution of the sensory symptoms included hands and feet in 27% of the patients, torso in 27%, legs only in 23%, face in 17% and arms only in 10%. For five patients, the sensory disturbance was migratory and affected different parts of the body at any given time. After the introduction of a gluten-free diet, 77% of patients noted significant improvement in their sensory symptoms. In one-third of the patients, there was a complete resolution of the sensory symptoms. CONCLUSION: Unexplained sensory symptoms can be seen in patients with gluten sensitivity and respond to strict adherence to a gluten-free diet.

Sensory experiences questionnaire unravels differences in sensory profiles between MECP2-related disorders.

The methyl CpG-binding protein-2 (MECP2) gene is located on the Xq28 region. Loss of function mutations or increased copies of MECP2 result in Rett syndrome (RTT) and MECP2 duplication syndrome (MDS), respectively. Individuals with both disorders exhibit overlapping autism symptoms, yet few studies have dissected the differences between these gene dosage sensitive disorders. Further, research examining sensory processing patterns in persons with RTT and MDS is largely absent. Thus, the goal of this study was to analyze and compare sensory processing patterns in persons with RTT and MDS. Towards this goal, caregivers of 50 female individuals with RTT and 122 male individuals with MDS, between 1 and 46 years of age, completed a standardized measure of sensory processing, the Sensory Experiences Questionnaire. Patterns detected in both disorders were compared against each other and against normative values. We found sensory processing abnormalities for both hyper- and hypo-sensitivity in both groups. Interestingly, abnormalities in MDS were more pronounced compared with in RTT, particularly with items concerning hypersensitivity and sensory seeking, but not hyposensitivity. Individuals with MDS also exhibited greater sensory symptoms compared with RTT in the areas of tactile and vestibular sensory processing and for both social and nonsocial stimuli. This study provides a first description of sensory symptoms in individuals with RTT and individuals with MDS. Similar to other neurodevelopmental disorders, a variety of sensory processing abnormalities was found. These findings reveal a first insight into sensory processing abnormalities caused by a dosage sensitive gene and may ultimately help guide therapeutic approaches for these disorders.

Relative contribution of sensory and motor deficits on grip force control in patients with chronic stroke.

OBJECTIVE: This study aimed to characterize grasping behavior in static (weight-dependent modulation and stability of control) and dynamic (predictive control) aspects specifically focusing on the relative contribution of sensory and motor deficits to grip force control in patients with chronic stroke. METHODS: Twenty-four chronic stroke patients performed three manipulative tasks: five trials of 5-s grasp-lift-holding, 30-s static holding, and vertical dynamic/cyclic oscillation of holding the object. RESULTS: Exerted static grip force on the paretic side exhibited statistically greater than that on the non-paretic side. Spearman's rank correlation coefficient revealed that the contribution to static grip force control was larger in sensory deficits than in motor deficits. In addition, the sensory deficit is related to the reduced coupling between grip force and load force, suggesting difficulty in predictive control due to the absence of sensory feedback. CONCLUSIONS: Given that grip force control involves predictive feedforward and online feedback control, the evaluation of grip force might be an important and feasible evaluation manner for the assessment of sensorimotor control in patients post-stroke. SIGNIFICANCE: Detailed evaluation of grip force control would help to understand the mechanisms underlying hand dysfunction in stroke patients.

Sensory disturbances in Creutzfeldt-Jakob disease.

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disease characterized by rapidly progressive dementia, motor impairments, and psychiatric symptoms. Sensory disturbances were occasionally reported as well. The study aims to describe the sensory symptoms of the disease. METHODS: The CJD Israeli National Database was screened for patients who presented sensory symptoms throughout the disease course. Symptoms, characteristics, and distribution were reviewed and the demographic and clinical data (sex, etiologies of the disease, age of onset, disease duration, neurological exam finding, tau protein level, EEG and MRI findings) were compared with the demographics and clinical data of CJD without sensory symptoms. Then, the patients with sensory symptoms were divided into patients with symptom distribution consistent with peripheral nervous system (PNS) involvement and central nervous system (CNS) involvement. The demographics and clinical data of the 2 groups were compared. RESULTS: Eighty-four CJD patients with sensory symptoms and 645 CJD patients without sensory symptoms were included in the study. Sensory symptoms were more common in genetic E200K CJD patients (14.6% vs. 5.6% respectively, p = 0.0005) (chi-squared test). Numbness and neuropathic pain were the most common symptoms and distribution of symptoms of "stocking gloves" with decreased deep tendon reflexes suggesting peripheral neuropathy in 44% of the patients. In these patients, the classical EEG findings of Periodic Sharp Wave Complexes were less often found (58% vs. 22%, p = 0.02) (chi-squared test). CONCLUSIONS: Sensory symptoms are more common in E200K patients and often follow peripheral neuropathy distribution that suggests PNS involvement.

RFC1 repeat expansions and cerebellar ataxia, neuropathy and vestibular areflexia syndrome: Experience and perspectives from a neuromuscular disorders unit.

INTRODUCTION: Pathogenic expansions in RFC1 have been described as a cause of a spectrum of disorders including late-onset ataxia, chronic cough, and cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). Sensory neuronopathy/neuropathy appears to be a major symptom of RFC1-disorder, and RFC1 expansions are common in patients with sensory chronic idiopathic axonal neuropathy or sensory ganglionopathy. We aimed to investigate RFC1 expansions in patients with suspected RFC1-related disease followed-up in a Neuromuscular Diseases Unit, with a particular interest in the involvement of the peripheral nervous system. METHODS: We recruited twenty consecutive patients based on the presence of at least two of the following features: progressive ataxia, sensory neuropathy/neuronopathy, vestibulopathy and chronic cough. Medical records were retrospectively reviewed for a detailed clinical description. More extensive phenotyping of the RFC1-positive patients and clinical comparison between RFC1 positive and negative patients were performed. RESULTS: Biallelic AAGGG repeat expansions were identified in 13 patients (65%). The most frequent symptoms were chronic cough and sensory disturbances in the lower extremities (12/13). Only 4 patients (31%) had complete CANVAS. The phenotypes were sensory ataxia and sensory symptoms in extremities in 4/13; sensory ataxia, sensory symptoms, and vestibulopathy in 3/13; sensory symptoms plus chronic cough in 2/13. Chronic cough and isolated sensory neuronopathy were significantly more prevalent in RFC1-positive patients. CONCLUSION: Pathogenic RFC1 expansions are a common cause of sensory neuropathy/neuronopathy and should be considered in the approach to these patients. Identification of key symptoms or detailed interpretation of nerve conduction studies may improve patient selection for genetic testing.

Sensory sensitivity after acquired brain injury: A systematic review.

Patients with acquired brain injury frequently report experiencing sensory stimuli as abnormally under- (sensory hyposensitivity) or overwhelming (sensory hypersensitivity). Although they can negatively impact daily functioning, these symptoms are poorly understood. To provide an overview of the current evidence on atypical sensory sensitivity after acquired brain injury, we conducted a systematic literature review. The primary aim of the review was to investigate the behavioural and neural mechanisms that are associated with self-reported sensory sensitivity. Studies were included when they studied sensory sensitivity in acquired brain injury populations, and excluded when they were not written in English, consisted of non-empirical research, did not study human subjects, studied pain, related sensory sensitivity to peripheral injury or studied patients with a neurodegenerative disorder, meningitis, encephalitis or a brain tumour. The Web of Science, PubMed and Scopus databases were searched for appropriate studies. A qualitative synthesis of the results of the 81 studies that were included suggests that abnormal sensory thresholds and a reduced information processing speed are candidate behavioural mechanisms of atypical subjective sensory sensitivity after acquired brain injury. Furthermore, there was evidence for an association between subjective sensory sensitivity and structural grey or white matter abnormalities, and to functional abnormalities in sensory cortices. However, further research is needed to explore the causation of atypical sensory sensitivity. In addition, there is a need for the development of adequate diagnostic tools. This can significantly advance the quantity and quality of research on the prevalence, aetiology, prognosis and treatment of these symptoms.

Postural performance assessment in aging people with diabetes and diabetic peripheral neuropathy using a Wii balance board.

PURPOSE: To determine the effect of sensory perturbations on static postural control in older people with type 2 diabetes mellitus by comparing postural outcomes of people with and without diabetic neuropathy using a Wii Balance Board (WBB). MATERIALS AND METHODS: Static postural balance assessments were performed in 31 participants: nine with type 2 diabetes mellitus; 12 with diabetic neuropathy; and 10 non-diabetic controls. Participants stood on the WBB under sensory perturbations (visual and proprioceptive). Body balance was analysed using centre of pressure ellipse area, mean velocity, and sample entropy. The effects of within-participant factors, sensory perturbations and the between-participants factor 'group' on outcomes were analysed using a multivariate analysis of variance model. RESULTS: Type 2 diabetes mellitus participants with and without neuropathy showed altered postural performance under sensory perturbations compared to non-diabetic participants. Moreover, participants with diabetic neuropathy showed impaired postural performance when one perceptual system was disturbed. Finally, participants with type 2 diabetes mellitus without neuropathy decreased their postural performance when both sensory disturbances were present. CONCLUSIONS: The Wii Balance Board can be a useful alternative for balance impairment screening related to diabetic neuropathy and contribute as an affordable source of insight in early interventions in integral diabetes care.Implications to rehabilitationOlder people with diabetic peripheral neuropathy depend on visual and somatosensory cues to keep their static postural balance.Static balance assessment using the Wii Balance Board allows the identification of alterations in postural performance in participants with diabetes.This low-cost method used can be considered as a complement to integral diabetes care.

[Motor Neuron Involvement in RFC1 CANVAS/Spectrum Disorders].

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is characterized by the triad of cerebellar ataxia, bilateral vestibular impairment, and sensory neuropathy. The responsible anatomical region for the sensory disturbance in CANVAS is reportedly the dorsal root ganglion, which suggests neuronopathy rather than neuropathy as the pathomechanism of this peripheral nervous system disorder. Early on, motor neuron involvement was considered rare in CANVAS. The etiology of CANVAS includes the homozygous pentanucleotide repeat expansion within the RFC1 gene, resulting in diverse phenotypes and motor deficits such as brisk reflex, extensor plantar responses, or spasticity of the upper motor neurons and muscle wasting, weakness, cramp, or fasciculation of the lower motor neurons. CANVAS patients with AAGGG repeat expansions may show motor neuron involvement, with considerable variation in the reported frequencies. In contrast, although some patients with ACAGG repeat expansions also show motor neuron involvement, its frequency remains elusive.

Severe distinct dysautonomia in RFC1-related disease associated with Parkinsonism.

Biallelic repeat expansions in replication factor C subunit 1 (RFC1) have recently been found to cause cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS). Additional features that have been described include Parkinsonism and a multiple system atrophy (MSA)-like syndrome. CANVAS can include features of dysautonomia, but they are much milder than typically seen in MSA. We report a detailed autonomic phenotype of multisystem RFC1-related disease presenting initially as CANVAS. Our patient presented aged 61 with a sensory ataxic neuropathy who rapidly developed widespread autonomic failure and Parkinsonism. The autonomic profile was of a mixed pre- and post-ganglionic syndrome with progressive involvement of sympathetic and parasympathetic cardiovascular and sudomotor function. The Parkinsonism did not respond to levodopa. We present a patient with CANVAS and biallelic RFC1 expansions who developed Parkinsonism with severe autonomic involvement similar to that seen in classical MSA. The link between MSA and CANVAS remains uncertain.

Impact of great auricular nerve sacrifice on sensory disturbance after parotidectomy.

PURPOSE: To investigate the association between great auricular nerve (GAN) sacrifice during parotidectomy and postoperative sensory disturbance. MATERIALS AND METHODS: Patients who underwent parotidectomy between November 2016 and May 2020 at a single academic institution were included in this retrospective chart review. Operative notes were reviewed to determine incidence of GAN sacrifice. Prevalence of patient-reported sensory complaints in the GAN distribution and time to spontaneous resolution of symptoms were assessed. RESULTS: Of 305 parotidectomy patients, 111 (36.4%) endorsed complaints of postoperative sensory disturbances in the GAN distribution typically characterized by numbness or shooting pains. GAN sacrifice was present in 9 (8.1%) of 111 patients who experienced sensory disturbances compared to 9 (4.6%) who reported no sensory disturbances (p > 0.05). Twenty-five patients (32.5%) experienced spontaneous resolution of symptoms at their most recent follow-up at a mean of 6.2 months after onset of symptoms. Of those that experienced a sensory disturbance, GAN preservation was not significantly associated with likelihood of spontaneous recovery (p > 0.05). CONCLUSIONS: We report the largest series to date of post-operative sensory disturbance in parotidectomy patients as it relates to intraoperative GAN sacrifice. Although the relationship between GAN sacrifice and the incidence of postoperative sensory disturbance and its subsequent resolution were not significant, we continue to advocate for GAN preservation to reduce incidence of postoperative sensory disturbances.

Biomechanical measures of clinician-defined unsteadiness during a forward stepdown task in individuals post-arthroscopy for femoroacetabular impingement syndrome.

BACKGROUND: Patients with femoroacetabular impingement syndrome can present with aberrant movement patterns including unsteady balance. Balance training is included in rehabilitation after hip arthroscopy and may improve quality of movement; however, specific biomechanical measures associated with clinician-defined balance impairments are unknown. We aimed to understand these associations as they may inform targeted rehabilitative interventions. METHODS: The forward stepdown is a clinical test used to evaluate movement quality, including balance. 23 individuals at least one-year post-arthroscopy for femoroacetabular impingement syndrome and 15 healthy comparisons performed the forward stepdown, recorded by 3-dimensional motion capture and 2-dimensional video. Three physical therapists graded the 2-dimensional video for steadiness. Two-way analyses of variance were used to evaluate the interaction of group (post-arthroscopy/healthy comparison) by steadiness (steady/unsteady), for center of pressure medial-lateral excursion, center of pressure path length, and lateral trunk, pelvis, and lower extremity joint excursions. FINDINGS: Six (26.1%) participants post-arthroscopy and five (33.3%) healthy comparisons were categorized as unsteady. The odds of being categorized as unsteady were not greater for participants post-arthroscopy (P = 0.72). There were no significant interactions; however, participants with clinician-defined unsteady balance, regardless of group, had significantly greater frontal plane trunk excursion, greater hip excursion, and greater center of pressure path length than those with steady balance (P ≤ 0.006). INTERPRETATION: The odds of being categorized as unsteady were not greater for individuals post-arthroscopy for femoroacetabular impingement syndrome. Clinician-defined unsteadiness was associated with greater frontal plane trunk and hip motion which may be rehabilitation targets to improve balance during a dynamic single-leg task.

Subgrouping of Peripheral Neuropathic Pain Patients According to Sensory Symptom Profile Using the Korean Version of the PainDETECT Questionnaire.

BACKGROUND: A culturally validated Korean version of the PainDETECT Questionnaire (PD-Q) was used to identify neuropathic pain components (NeP) in patients suffering from chronic pain. The purpose of this study was to determine if the Korean PD-Q can be used to subgroup patients with peripheral NeP according to sensory symptom profiles. METHODS: This study included 400 Korean patients with peripheral neuropathic pain diagnosed as probable or definite NeP. The total scores and subscores for each item in PD-Q were transformed into a Z-score for standardization. Hierarchical cluster analysis was performed to identify clusters of subjects by PD-Q scores. RESULTS: The mean total PD-Q score of the study participants was 14.57 ± 6.46. A hierarchical cluster analysis identified 5 clusters with distinct pain characteristic profiles. Cluster 1 had relatively severe burning and tingling sensations. The mean total PD-Q score for cluster 2 was the lowest of the 5 clusters. Cluster 3 tended to be vulnerable to pain in response to cold/heat stimulation. Cluster 4 showed relatively severe pain induced by physical stimuli, such as light touch or slight pressure. Cluster 5 had high scores for all NeP symptoms. CONCLUSION: This study demonstrates the ability of patients to cluster by symptoms using the Korean PD-Q. Subgrouping of peripheral neuropathic pain by sensory symptom profile may be useful in making effective drug treatment decisions.

Assessing Multisensory Sensitivity Across Scales: Using the Resulting Core Factors to Create the Multisensory Amplification Scale.

Multisensory sensitivity (MSS), observed in some chronic pain patients, may reflect a generalized central nervous system sensitivity. While several surveys measure aspects of MSS, there remains no gold standard. We explored the underlying constructs of 4 MSS-related surveys (80 items in total) using factor analyses using REDCap surveys (N = 614, 58.7% with pain). Four core- and 6 associated-MSS factors were identified from the items assessed. None of these surveys addressed all major sensory systems and most included additional related constructs. A revised version of the Somatosensory Amplification Scale was developed, encompassing 5 core MSS systems: vision, hearing, smell, tactile, and internal bodily sensations: the 12-item Multisensory Amplification Scale (MSAS). The MSAS demonstrated good internal consistency (alpha = 0.82), test-retest reliability (ICC3,1 = 0.90), and construct validity in the original and in a new, separate cohort (R = 0.54-0.79, P < .0001). Further, the odds of having pain were 2-3.5 times higher in the highest sex-specific MSAS quartile relative to the lowest MSAS quartile, after adjusting for age, sex, BMI, and pain schema (P < .03). The MSAS provides a psychometrically comprehensive, brief, and promising tool for measuring the core-dimensions of MSS. PERSPECTIVE: Multiple multisensory sensitivity (MSS) tools are used, but without exploration of their underlying domains. We found several measures lacking core MSS domains, thus we modified an existing scale to encompass 5 core MSS domains: light, smell, sound, tactile, and internal bodily sensations using only 12 items, with good psychometric properties.

Identifying Discomplete Spinal Lesions: New Evidence from Pain-Autonomic Interaction in Spinal Cord Injury.

The clinical evaluation of spinal afferents is an important diagnostic and prognostic marker for neurological and functional recovery after spinal cord injury (SCI). Particularly important regarding neuropathic pain following SCI is the function of the spinothalamic tract (STT) conveying nociceptive and temperature information. Here, we investigated the added value of neurophysiological methods revealing discomplete STT lesions; that is, residual axonal sparing in clinically complete STT lesions. Specifically, clinical pinprick testing and thermal thresholds were compared with objective contact heat-evoked potentials (CHEPs) and a novel measure of pain-autonomic interaction employing heat-induced sympathetic skin responses (SSR). The test stimuli (i.e., contact heat, pinprick) were applied below the lesion level in 32 subjects with thoracic SCI while corresponding heat-evoked responses (i.e., CHEPs and SSR) were recorded above the lesion (i.e., scalp and hand, respectively). Readouts of STT function were related to neuropathic pain characteristics. In subjects with abolished pinprick sensation, measures of thermosensation (10%), CHEPs (33%), and SSR (48%) revealed residual STT function. Importantly, SSRs can be used as an objective readout and when abolished, no other proxy indicated residual STT function. No relationship was found between STT function readouts and spontaneous neuropathic pain intensity and extent. However, subjects with clinically preserved STT function presented more often with allodynia (54%) than subjects with discomplete (13%) or complete STT lesions (18%). In individuals with absent pinprick sensation, discomplete STT lesions can be revealed employing pain-autonomic measures. The improved sensitivity to discerning STT lesion completeness might support the investigation of its association with neuropathic pain following SCI.

Distinct hippocampal subfield atrophy in Parkinson's disease regarding motor subtypes.

INTRODUCTION: Global hippocampal atrophy has been repeatedly reported in patients with Parkinson's disease (PD). However, there is limited literature on the differential involvement of hippocampal subfields among PD motor subtypes. This study aimed to investigate hippocampal subfield alterations in patients with PD based on their predominant symptoms. METHOD: We enrolled 31 PD patients with the tremor-dominant (TD) subtype, 27 PD patients with postural instability and gait disturbance-dominant (PIGD) subtype, and 40 healthy controls (HCs). All participants underwent high-spatial-resolution T1-weighted magnetic resonance imaging. The volume of hippocampal subfields was measured using FreeSurfer software, compared across groups, and correlated with clinical features. RESULTS: We found volumetric reductions in the hippocampal subfield in both patient subtypes compared to HCs, which were more pronounced in the PIGD subtype. The PIGD subtype had accelerated age-related alterations in the hippocampus compared to the TD subtype. Bilateral hippocampal volumes were positively associated with cognitive performance levels, but not with disease severity and duration in patients. CONCLUSIONS: Alterations in the hippocampal subfields of patients with PD differed based on their predominant symptoms. These findings are of relevance for understanding the pathophysiology of the increased risk of cognitive impairment in PIGD.

Postural and gait symptoms in de novo Parkinson's disease patients correlate with cholinergic white matter pathology.

INTRODUCTION: The postural instability gait difficulty motor subtype of patients with Parkinson's disease (PIGD-PD) has been associated with more severe cognitive pathology and a higher risk on dementia compared to the tremor-dominant subtype (TD-PD). Here, we investigated whether the microstructural integrity of the cholinergic projections from the nucleus basalis of Meynert (NBM) was different between these clinical subtypes. METHODS: Diffusion-weighted imaging data of 98 newly-diagnosed unmedicated PD patients (44 TD-PD and 54 PIGD-PD subjects) and 10 healthy controls, were analysed using diffusion tensor imaging, focusing on the white matter tracts associated with cholinergic projections from the NBM (NBM-WM) as the tract-of-interest. Quantitative tract-based and voxel-based analyses were performed using FA and MD as the estimates of white matter integrity. RESULTS: Voxel-based analyses indicated significantly lower FA in the frontal part of the medial and lateral NBM-WM tract of both hemispheres of PIGD-PD compared to TD-PD. Relative to healthy control, several clusters with significantly lower FA were observed in the frontolateral NBM-WM tract of both disease groups. Furthermore, significant correlations between the severity of the axial and gait impairment and NBM-WM FA and MD were found, which were partially mediated by NBM-WM state on subjects' attentional performance. CONCLUSIONS: The PIGD-PD subtype shows a loss of microstructural integrity of the NBM-WM tract, which suggests that a loss of cholinergic projections in this PD subtype already presents in de novo PD patients.

Subjective sensory sensitivity and its relationship with anxiety in people with probable migraine.

OBJECTIVE: To better characterize differences in interictal sensory experience in adults with migraine and more comprehensively describe the relevance of anxiety to these experiences. BACKGROUND: Evidence suggests that sensitivity to sensory input may not be limited to migraine attacks but continues between them. However, there is a need to better understand whether this is the case across senses, and to clearly distinguish sensory experience from measured sensory threshold, which are not straightforwardly related. Previous literature also indicates a co-occurrence between sensory sensitivity, migraine, and anxiety, but this relationship remains to be fully elucidated. METHODS: The present cross-sectional study used online questionnaires to investigate how self-reported sensory experiences relate to migraine in a large community sample including 117 individuals with probable migraine and 827 without. Mediation analyses were also used to determine whether any relationship between migraine and sensory sensitivity was mediated by anxiety. RESULTS: Significant increases in subjective reports of sensory sensitivity (d = 0.80) and sensory avoidance (d = 0.71) were found in participants with migraine. Anxiety symptoms partially mediated the relationship between subjective sensory sensitivity and migraine. Finally, visual, movement, and auditory subscales were found to provide unique explanatory variance in analyses predicting the incidence of migraine (area under the curve = 0.73, 0.69, 0.62 respectively). CONCLUSION: Subjective sensory sensitivities are present between attacks and across senses in individuals with migraine. Anxiety symptoms are relevant to this relationship; however, sensory sensitivities appear to exist independent of this affective influence. The implications of interictal sensitivities for the daily lives of those with migraine should, therefore, be considered in clinical management wherever appropriate.

Dual-task clinical and functional MRI correlates in Parkinson's disease with postural instability and gait disorders.

BACKGROUND: Dual-task is a challenge for Parkinson's disease patients with postural instability and gait disorders (PD-PIGD). OBJECTIVE: This study investigated clinical, cognitive and functional brain correlates of dual-task deficits in PD-PIGD patients using quantitative gait analysis, neuropsychological evaluations and functional MRI (fMRI). METHODS: Twenty-three PD-PIGD patients performed a clinical assessment of gait/balance abilities. Single and dual-task Timed-Up-and-Go tests were monitored using an optoelectronic system to study turning velocity. Patients underwent executive-attentive function evaluation and two fMRI tasks: motor-task (foot anti-phase movements), and dual-task (foot anti-phase movements while counting backwards by threes starting from 100). Twenty-three healthy subjects underwent neuropsychological and fMRI assessments. RESULTS: Dual-task in PD-PIGD patients resulted in worse gait performance, particularly during turning. Performing the dual-task relative to the motor-fMRI task, healthy subjects showed widespread increased recruitment of sensorimotor, cognitive and cerebellar areas and reduced activity of inferior frontal and supramarginal gyri, while PD-PIGD patients showed increased recruitment of inferior frontal gyrus and supplementary motor area and reduced activity of primary motor, supramarginal and caudate areas. Dual-task gait alterations in patients correlated with balance and executive deficits and with altered dual-task fMRI brain activity of frontal areas. CONCLUSIONS: This study suggested the correlation between dual-task gait difficulties, postural instability and executive dysfunction in PD-PIGD patients. FMRI results suggest that an optimized recruitment of motor and cognitive networks is associated with a better dual-task performance in PD-PIGD. Future studies should evaluate the effect of specific gait/balance and dual-task trainings to improve gait parameters and optimize brain functional activity during dual-tasks.

Non-pharmacological interventions for spatial neglect or inattention following stroke and other non-progressive brain injury.

BACKGROUND: People with spatial neglect after stroke or other brain injury have difficulty attending to one side of space. Various rehabilitation interventions have been used, but evidence of their benefit is unclear. OBJECTIVES: The main objective was to determine the effects of non-pharmacological interventions for people with spatial neglect after stroke and other adult-acquired non-progressive brain injury. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last searched October 2020), the Cochrane Central Register of Controlled Trials (CENTRAL; last searched October 2020), MEDLINE (1966 to October 2020), Embase (1980 to October 2020), the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1983 to October 2020), and PsycINFO (1974 to October 2020). We also searched ongoing trials registers and screened reference lists. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of any non-pharmacological intervention specifically aimed at spatial neglect. We excluded studies of general rehabilitation and studies with mixed participant groups, unless separate neglect data were available. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Review authors categorised the interventions into eight broad types deemed to be applicable to clinical practice through iterative discussion: visual interventions, prism adaptation, body awareness interventions, mental function interventions, movement interventions, non-invasive brain stimulation, electrical stimulation, and acupuncture. We assessed the quality of evidence for each outcome using the GRADE approach. MAIN RESULTS: We included 65 RCTs with 1951 participants, all of which included people with spatial neglect following stroke. Most studies measured outcomes using standardised neglect assessments. Fifty-one studies measured effects on ADL immediately after completion of the intervention period; only 16 reported persisting effects on ADL (our primary outcome). One study (30 participants) reported discharge destination, and one (24 participants) reported depression. No studies reported falls, balance, or quality of life. Only two studies were judged to be entirely at low risk of bias, and all were small, with fewer than 50 participants per group. We found no definitive (phase 3) clinical trials. None of the studies reported any patient or public involvement. Visual interventions versus any control: evidence is very uncertain about the effects of visual interventions for spatial neglect based on measures of persisting functional ability in ADL (2 studies, 55 participants) (standardised mean difference (SMD) -0.04, 95% confidence interval (CI) -0.57 to 0.49); measures of immediate functional ability in ADL; persisting standardised neglect assessments; and immediate neglect assessments. Prism adaptation versus any control: evidence is very uncertain about the effects of prism adaptation for spatial neglect based on measures of persisting functional ability in ADL (2 studies, 39 participants) (SMD -0.29, 95% CI -0.93 to 0.35); measures of immediate functional ability in ADL; persisting standardised neglect assessments; and immediate neglect assessments. Body awareness interventions versus any control: evidence is very uncertain about the effects of body awareness interventions for spatial neglect based on measures of persisting functional ability in ADL (5 studies, 125 participants) (SMD 0.61, 95% CI 0.24 to 0.97); measures of immediate functional ability in ADL; persisting standardised neglect assessments; immediate neglect assessments; and adverse events. Mental function interventions versus any control: we found no trials of mental function interventions for spatial neglect reporting on measures of persisting functional ability in ADL. Evidence is very uncertain about the effects of mental function interventions on spatial neglect based on measures of immediate functional ability in ADL and immediate neglect assessments. Movement interventions versus any control: we found no trials of movement interventions for spatial neglect reporting on measures of persisting functional ability in ADL. Evidence is very uncertain about the effects of body awareness interventions on spatial neglect based on measures of immediate functional ability in ADL and immediate neglect assessments. Non-invasive brain stimulation (NIBS) versus any control: evidence is very uncertain about the effects of NIBS on spatial neglect based on measures of persisting functional ability in ADL (3 studies, 92 participants) (SMD 0.35, 95% CI -0.08 to 0.77); measures of immediate functional ability in ADL; persisting standardised neglect assessments; immediate neglect assessments; and adverse events. Electrical stimulation versus any control: we found no trials of electrical stimulation for spatial neglect reporting on measures of persisting functional ability in ADL. Evidence is very uncertain about the effects of electrical stimulation on spatial neglect based on immediate neglect assessments. Acupuncture versus any control: we found no trials of acupuncture for spatial neglect reporting on measures of persisting functional ability in ADL. Evidence is very uncertain about the effects of acupuncture on spatial neglect based on measures of immediate functional ability in ADL and immediate neglect assessments. AUTHORS' CONCLUSIONS: The effectiveness of non-pharmacological interventions for spatial neglect in improving functional ability in ADL and increasing independence remains unproven. Many strategies have been proposed to aid rehabilitation of spatial neglect, but none has yet been sufficiently researched through high-quality fully powered randomised trials to establish potential or adverse effects. As a consequence, no rehabilitation approach can be supported or refuted based on current evidence from RCTs. As recommended by a number of national clinical guidelines, clinicians should continue to provide rehabilitation for neglect that enables people to meet their rehabilitation goals. Clinicians and stroke survivors should have the opportunity, and are strongly encouraged, to participate in research. Future studies need to have appropriate high-quality methodological design, delivery, and reporting to enable appraisal and interpretation of results. Future studies also must evaluate outcomes of importance to patients, such as persisting functional ability in ADL. One way to improve the quality of research is to involve people with experience with the condition in designing and running trials.

Symptoms, complications and management of long COVID: a review.

Globally, there are now over 160 million confirmed cases of COVID-19 and more than 3 million deaths. While the majority of infected individuals recover, a significant proportion continue to experience symptoms and complications after their acute illness. Patients with 'long COVID' experience a wide range of physical and mental/psychological symptoms. Pooled prevalence data showed the 10 most prevalent reported symptoms were fatigue, shortness of breath, muscle pain, joint pain, headache, cough, chest pain, altered smell, altered taste and diarrhoea. Other common symptoms were cognitive impairment, memory loss, anxiety and sleep disorders. Beyond symptoms and complications, people with long COVID often reported impaired quality of life, mental health and employment issues. These individuals may require multidisciplinary care involving the long-term monitoring of symptoms, to identify potential complications, physical rehabilitation, mental health and social services support. Resilient healthcare systems are needed to ensure efficient and effective responses to future health challenges.