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.

Abnormal cortical responses elicited by audiovisual movies in patients with autism spectrum disorder with atypical sensory behavior: A magnetoencephalographic study.

BACKGROUND: Atypical sensory behavior disrupts behavioral adaptation in children with autism spectrum disorder (ASD); however, neural correlates of sensory dysfunction using magnetoencephalography (MEG) remain unclear. METHOD: We used MEG to measure the cortical activation elicited by visual (uni)/audiovisual (multisensory) movies in 46 children (7-14 years) were included in final analysis: 13 boys with atypical audiovisual behavior in ASD (AAV+), 10 without this condition, and 23 age-matched typically developing boys. RESULTS: The AAV+ group demonstrated an increase in the cortical activation in the bilateral insula in response to unisensory movies and in the left occipital, right superior temporal sulcus (rSTS), and temporal regions to multisensory movies. These increased responses were correlated with severity of the sensory impairment. Increased theta-low gamma oscillations were observed in the rSTS in AAV+. CONCLUSION: The findings suggest that AAV is attributed to atypical neural networks centered on the rSTS.

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.

Self-reported dual sensory impairment, dementia, and functional limitations in Medicare beneficiaries.

BACKGROUND: Vision and hearing impairments often co-exist with dementia, and all are independently associated with limitations in daily activities. Our aim was to examine the association of dual sensory impairment with functional limitations, and further examine the combined estimated association of sensory impairment and dementia with these functional limitations. METHODS: Cross-sectional analysis of the National Health and Aging Trends Study (NHATS), a population-based cohort of Medicare beneficiaries, was performed. Participants were selected from the 2015 round. Survey weighted Poisson regression models adjusted for dementia, demographics, and health status variables examined the association of self-reported dual sensory impairment (no sensory impairment, single sensory impairment, dual sensory impairment) with scores of limitations in mobility, self-care, and household activities. Models were repeated to take into account the combined effects of dual sensory impairment and dementia. RESULTS: Overall, 7124 participants representative of Medicare beneficiaries 65 years or older were included. Of them, 43.9% were 75 years or older and 55.3% were female. Older adults with dual sensory impairment had greater limitations with mobility (prevalence rate ratio [PRR] = 1.45, 95% CI = 1.28-1.63), self-care (PRR = 1.41, 95% CI = 1.25-1.59), and household activities (PRR = 1.54, 95% CI = 1.37-1.72) compared with those without sensory impairment. They also had greater limitations than those with a single sensory impairment across the different activity categories. In models taking into account the combined estimated effect of both sensory impairment and dementia, those with dual sensory impairment and dementia had greater limitations than those without sensory impairment or dementia in each category (mobility: PRR = 1.85, 95% CI = 1.59-2.14, self-care: PRR = 1.86, 95% CI = 1.59-2.18, household: PRR = 2.41, 95% CI = 2.09-2.77). CONCLUSIONS: Older adults with dual sensory impairment had greater functional limitations compared with those without sensory impairment and those with a single sensory impairment. Strategies to improve visual and/or hearing function (e.g., sensory aids, rehabilitation) could potentially help prevent or minimize disability, even among those with dementia.

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.

Ear fullness characteristics and prognosis in patients with all-frequency sudden sensorineural hearing loss.

OBJECTIVE: This study investigated the characteristics and prognosis of the feeling of ear fullness in patients with unilateral all-frequency sudden sensorineural hearing loss. METHODS: Our study included 56 patients with a diagnosis of unilateral all-frequency sudden sensorineural hearing loss accompanied by a feeling of ear fullness and 48 patients without a feeling of ear fullness. The condition of these patients was prospectively observed. RESULTS: Positive correlations were observed between grading of feeling of ear fullness and hearing loss in patients with a feeling of ear fullness (r = 0.599, p < 0.001). No significant differences were observed in the total effective rate of hearing recovery between patients with and without a feeling of ear fullness after one month of treatment (Z = -0.641, p = 0.521). Eighty-six per cent of patients (48 out of 56) showed complete recovery from the feeling of ear fullness. There was no correlation between feeling of ear fullness recovery and hearing recovery (r = 0.040, p = 0.769). CONCLUSION: The prognosis of feeling of ear fullness is good. There was no correlation between feeling of ear fullness recovery and hearing recovery for all-frequency sudden sensorineural hearing loss patients.

Repercussions of the Degrees of Hearing Loss and Vestibular Dysfunction on the Static Balance of Children With Sensorineural Hearing Loss.

OBJECTIVE: The purpose of this study was to assess the static balance of children with sensorineural hearing loss (SNHL) according to the degrees of SNHL and the function of the vestibular system. METHODS: This cross-sectional study was conducted in public schools located in Caruaru, Pernambuco state, Brazil, with 130 children (65 with normal hearing and 65 with SNHL as documented by air and bone conduction audiometry) of both sexes between 7 and 11 years old. Static balance was assessed by a stabilometric analysis using a force platform consisting of the circular area of center-of-pressure displacement of the children evaluated in 3 positions: bipedal support with feet together and parallel (PF), tandem feet (TF), and 1 foot (OF), carried out under 2 sensory conditions each, with eyes open and eyes closed. After balance assessments, the children with SNHL received examinations of auditory and vestibular functions-through audiometry and computerized vectoelectronystagmography, respectively-to compose the groups according to degrees of SNHL and vestibular function. RESULTS: The children with severe and profound SNHL demonstrated more static balance instabilities than the children with normal hearing in 5 positions assessed with eyes open (PF, TF, and OF) and eyes closed (PF and TF). The same phenomenon occurred in children with SNHL and associated vestibular dysfunction in all of the positions assessed with eyes open and eyes closed (PF, TF, and OF). CONCLUSION: The larger the degree of SNHL, the greater the balance instability of the children. The children with SNHL and associated vestibular dysfunction showed the highest balance instabilities in this study. IMPACT: Children with larger degrees of SNHL and associated vestibular dysfunction might require prolonged periods to rehabilitate their balance.

Spinal Inhibitory Interneurons: Gatekeepers of Sensorimotor Pathways.

The ability to sense and move within an environment are complex functions necessary for the survival of nearly all species. The spinal cord is both the initial entry site for peripheral information and the final output site for motor response, placing spinal circuits as paramount in mediating sensory responses and coordinating movement. This is partly accomplished through the activation of complex spinal microcircuits that gate afferent signals to filter extraneous stimuli from various sensory modalities and determine which signals are transmitted to higher order structures in the CNS and to spinal motor pathways. A mechanistic understanding of how inhibitory interneurons are organized and employed within the spinal cord will provide potential access points for therapeutics targeting inhibitory deficits underlying various pathologies including sensory and movement disorders. Recent studies using transgenic manipulations, neurochemical profiling, and single-cell transcriptomics have identified distinct populations of inhibitory interneurons which express an array of genetic and/or neurochemical markers that constitute functional microcircuits. In this review, we provide an overview of identified neural components that make up inhibitory microcircuits within the dorsal and ventral spinal cord and highlight the importance of inhibitory control of sensorimotor pathways at the spinal level.

Non-Dolichoectatic Vertebral Artery Compression of the Medulla: A Comprehensive Literature Review.

OBJECTIVE: Vertebral artery compression of the medulla is a rare vascular finding that causes a variety of clinical presentations, from asymptomatic to neurological disability. This article presents the largest literature review to date on medullary compression of the vertebral arteries. METHODS: An English literature search was performed using the PubMed database and the keywords vertebral artery tortuosity, vertebral artery compression, and medullary compression. RESULTS: A comprehensive literature search yielded 68 patients (57% male) with medullary compression by an intracranial vertebral artery (ICVA). The left side of the medulla was compressed in 44, the right side in 19, and bilateral in 7. The most common clinical symptom was weakness - 26 patients (36%) - 6 had quadriparesis and 6 had hemiparesis. 21 patients reported imbalance; 12 various sensory symptoms; 4 patients were asymptomatic. CONCLUSIONS: Understanding the anatomy of the vasculature can help mitigate future debilitating stroke symptoms. Concrete guidelines for revascularization surgery in symptomatic patients may also be effective. Future studies are needed to further clarify the prevalence, natural history, vascular etiology, and treatment of this condition, including asymptomatic patients and the likelihood that they will develop further neurological signs and disability.

Effects of a 16-week Tai Chi intervention on cutaneous sensitivity and proprioception among older adults with and without sensory loss.

This study investigated the effects of a 16-week Tai Chi (TC) intervention on cutaneous sensitivity and proprioception among older adults with and without sensory loss. Thirty-six older adults were divided into sensory loss and control groups, and they underwent a 16-week TC intervention. Significant interactions were detected in heel cutaneous sensitivity (p = 0.046, F = 4.419) and knee flexion (p = 0.043, F = 4.580), extension (p = 0.027, F = 5.529) and ankle plantar-flexion proprioception (p = 0.037, F = 4.860). The post hoc test indicated that in the sensory loss group, heel cutaneous sensitivity threshold (p = 0.034) and knee flexion (p = 0.004), extension (p = 0.002) and ankle plantar-flexion (p = 0.023) proprioception threshold decreased at week 17, whereas in the control group, knee flexion (p = 0.029) proprioception threshold decreased at week 17. TC intervention improved cutaneous sensitivity at more sites and proprioception in more joints among the older adults with sensory loss. TC intervention is a good option for older adults to exercise, and it is more effective among older adults with sensory loss.

Body Lateropulsion in Stroke: Case Report and Systematic Review of Stroke Topography and Outcome.

INTRODUCTION: Body lateropulsion (BLP) is seen in neurological lesions involving the pathways responsible for body position and verticality. We report a case of isolated body lateropulsion (iBLP) as the presentation of lateral medullary infarction and conducted a systematic literature review. METHODS: MEDLINE and EMBASE databases were searched up to December 3, 2020. INCLUSION CRITERIA: age ≥ 18, presence of BLP, confirmed stroke on imaging. EXCLUSION CRITERIA: age < 18, qualitative reviews, studies with inadequate patient data. Statistical analysis was performed using IBM® SPSS® Statistics 20. RESULTS: A 64-year-old man presented with acute-onset iBLP. Brain MRI demonstrated acute infarction in the right caudolateral medulla. His symptoms progressed with ipsilateral Horner syndrome over the next 24 hours and contralateral hemisensory loss 10 days later. Repeat MRI showed an increase in infarct size. BLP resolved partially at discharge. Systematic review: 418 abstracts were screened; 59 studies were selected reporting 103 patients. Thirty-three patients had iBLP (32%). BLP was ipsilateral to stroke in 70 (68%) and contralateral in 32 (32%). The most common stroke locations were medulla (n = 63, 59%), pons (n = 16, 15%), and cerebellum (n = 16, 15%). Four strokes were cortical, 3 frontal and 1 temporoparietal (3%). The most common etiology was large-artery atherosclerosis (LAA) in 20 patients (32%), followed by small-vessel occlusion in 12 (19%). Seventeen (27%) had large-vessel occlusion (LVO), 12 involving the vertebral artery. Sixty (98%) had some degree of resolution of BLP; complete in 41 (70%). Median time-to-resolution was 14 days (IQR 10-21). There was no relationship between time-to-resolution and age, sex, side of BLP or side of stroke. CONCLUSION: BLP was commonly seen with medullary infarction and was the isolated finding in one-third. LAA and LVO were the most common etiologies. Recovery of BLP was early and complete in most cases.

Inhibition of TLR4 signaling protects mice from sensory and motor dysfunction in an animal model of autoimmune peripheral neuropathy.

BACKGROUND: While the etiology remains elusive, macrophages and T cells in peripheral nerves are considered as effector cells mediating autoimmune peripheral neuropathy (APN), such as Guillain-Barre syndrome. By recognizing both pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) signals, TLRs play a central role in the initiation of both innate and adaptive immune responses. In this study, we aimed to understand the involvement of TLR4 in the pathogenesis of APN and explore the potential of TLR4 as a drug target for therapeutic use. METHODS: APN was induced by a partial ligation on one of the sciatic nerves in B7.2 (L31) transgenic mice which possess a predisposed inflammatory background. APN pathology and neurological function were evaluated on the other non-injured sciatic nerve. RESULTS: TLR4 and its endogenous ligand HMGB1 were highly expressed in L31 mice, in circulating immune cells and in peripheral nerves. Enhanced TLR4 signaling was blocked with TAK 242, a selective TLR4 inhibitor, before and after disease onset. Intraperitoneal administration of TAK 242 not only inhibited monocyte, macrophage and CD8+ T cell activation, but also reduced the release of pro-inflammatory cytokines. TAK 242 protected mice from severe myelin and axonal loss, resulting in a remarkable improvement in mouse motor and sensory functions. TAK 242 was effective in alleviating the disease in both preventive and reversal paradigms. CONCLUSION: The study identified the critical contribution of TLR4-mediated macrophage activation in disease course and provided strong evidence to support TLR4 as a useful drug target for treating inflammatory autoimmune neuropathy.

Altered Processing of Complex Visual Stimuli in Patients with Postconcussive Visual Motion Sensitivity.

BACKGROUND AND PURPOSE: Vestibular symptoms are common after concussion. Vestibular Ocular Motor Screening identifies vestibular impairment, including postconcussive visual motion sensitivity, though the underlying functional brain alterations are not defined. We hypothesized that alterations in multisensory processing are responsible for postconcussive visual motion sensitivity, are detectable on fMRI, and correlate with symptom severity. MATERIALS AND METHODS: Twelve patients with subacute postconcussive visual motion sensitivity and 10 healthy control subjects underwent vestibular testing and a novel fMRI visual-vestibular paradigm including 30-second "neutral" or "provocative" videos. The presence of symptoms/intensity was rated immediately after each video. fMRI group-level analysis was performed for a "provocative-neutral" condition. Z-statistic images were nonparametrically thresholded using clusters determined by Z > 2.3 and a corrected cluster significance threshold of P = .05. Symptoms assessed on Vestibular Ocular Motor Screening were correlated with fMRI mean parameter estimates using Pearson correlation coefficients. RESULTS: Subjects with postconcussive visual motion sensitivity had significantly more Vestibular Ocular Motor Screening abnormalities and increased symptoms while viewing provocative videos. While robust mean activation in the primary and secondary visual areas, the parietal lobe, parietoinsular vestibular cortex, and cingulate gyrus was seen in both groups, selective increased activation was seen in subjects with postconcussive visual motion sensitivity in the primary vestibular/adjacent cortex and inferior frontal gyrus, which are putative multisensory visual-vestibular processing centers. Moderate-to-strong correlations were found between Vestibular Ocular Motor Screening scores and fMRI activation in the left frontal eye field, left middle temporal visual area, and right posterior hippocampus. CONCLUSIONS: Increased fMRI brain activation in visual-vestibular multisensory processing regions is selectively seen in patients with postconcussive visual motion sensitivity and is correlated with Vestibular Ocular Motor Screening symptom severity, suggesting that increased visual input weighting into the vestibular network may underlie postconcussive visual motion sensitivity.

Chemosensory Systems in COVID-19: Evolution of Scientific Research.

COVID-19 disease induced by coronavirus SARS-CoV-2 presents among its symptoms alterations of the chemosensory functions. In the first studies on the Chinese population, this symptomatology was not particularly relevant, and hyposmia and hypogeusia were excluded from the symptoms to be evaluated to diagnose the disease. With the pandemic spread of the illness, there has been an augment in reports on chemosensory dysfunctions among patients. The first data analysis showed the presence of these disorders mainly in paucisymptomatic and asymptomatic patients. The interest in chemosensory systems therefore increased considerably, because the olfactory and gustatory symptoms could be the key to stop the infection spread. Furthermore, the degree of alert and attention grew, considering that these types of dysfunctions are prognostic symptoms of serious neurodegenerative diseases. About 9 months have passed since the first anecdotal reports on the involvement of the olfactory and gustatory systems in the COVID-19 pathology. For this reason, a careful review of the literature was conducted to understand if it is clearer which people present chemosensory symptoms and if these are related to the severity of the disease. Furthermore, we have identified which aspects still remain to be clarified.

Subjective Evaluation of Balance by the Dizziness Handicap Inventory Does Not Predict Fall Risk in Older Adults Visiting Otolaryngology Clinics.

OBJECTIVES: Subjective symptoms of dizziness in older adults are affected not only by objective data such as postural balance, but also by complex psychological factors. Published data analyzing how simultaneous evaluations of both objective and subjective assessments of balance can predict fall risk remain lacking. This study examined how fall risk can be predicted based on both objective data for balance and hearing and subjective symptoms of dizziness among older adults visiting otolaryngology clinics. METHODS: Medical charts of 76 patients ≥65 years old with dizziness/vertigo who visited the otolaryngology clinic were reviewed. Objective data were evaluated by postural balance (posturographic data with eyes open and closed, and one-leg standing test), spontaneous nystagmus, and mean hearing levels. Subjective handicap associated with dizziness/vertigo was assessed using the Dizziness Handicap Inventory (DHI). Subjective mental status of anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). Information on history (cardiovascular diseases) and fall accidents within the preceding year was collected using an in-house interview sheet. RESULTS: Objective data on postural balance did not correlate with subjective symptoms on DHI or HADS (P > .05, Pearson's correlation coefficient). Adjusted logistic regression modeling with the outcome of incident falls revealed that poor postural balance significantly predicted fall risk (P < .05; 4.9 [1.4-16.8] per 10-cm2 increment). Nystagmus tended to be associated with fall risk. In contrast, DHI score did not predict fall risk (P = .43; 1.0 [0.9-1.03]). Receiver operating characteristic analysis proposed a cut-off for postural sway with eyes closed >6.1 cm2 as optimal to predict falls in patients with nystagmus (AUC, 0.74; 95% confidence interval, 0.48-0.997). CONCLUSION: Poor postural balance is associated with increased fall risk after adjusting for subjective symptoms in older adults at otolaryngology clinics. Conversely, the self-perceived dizziness handicap of DHI score is an insufficient tool to evaluate their fall risk.

Prediction of Balance After Inpatient Rehabilitation in Stroke Subjects with Severe Balance Alterations at the Admission.

BACKGROUND: Patients with severe motor alterations would be those on who the prediction of the expected motor response after inpatient rehabilitation programs is most required. OBJECTIVES: To analyze if the balance progress measured by the Berg Balance Scale and the time of hospitalization could be independent predictors of the Berg Balance at the end of a post stroke rehabilitation program in patients with severe balance alteration at the admission. Secondly, to compare a Berg Balance prediction model at the time of discharge based on the Berg Balance at the time of admission (model 1) to a Berg Balance prediction model at the time of discharge based on Berg Balance progress and the time of hospitalization (model 2). METHODS: Subjects suffering a first subacute supratentorial stroke admitted for inpatient rehabilitation between 2010 through 2018 were included to develop two linear regression models of predicted Berg Balance at discharge (n=149). RESULTS: According to model 1 (p < 0.0001, R2= 0.166), the Berg Balance at the admission would be a predictor of the Berg Balance at discharge from hospitalization. According to model 2 (p < 0.0001, R2= 0.993) the Berg Balance progress (ß= 1.026; p < 0.0001) and the hospitalization time (ß=-0.006; p < 0.0001) would be independent predictors of the Berg Balance at discharge. CONCLUSIONS: The motor response to the rehabilitation programs in subacute patients with severe motor alterations could be explained on the basis of balance condition at the admission, but this explanation may be improved considering the progress on the balance the patients achieve during inpatient rehabilitation irrespective the time of hospitalization.

A new ketogenic formulation improves functional outcome and reduces tissue loss following traumatic brain injury in adult mice.

Rationale: Traumatic brain injury (TBI) leads to neurological impairment, with no satisfactory treatments available. Classical ketogenic diets (KD), which reduce reliance on carbohydrates and provide ketones as fuel, have neuroprotective potential, but their high fat content reduces compliance, and experimental evidence suggests they protect juvenile brain against TBI, but not adult brain, which would strongly limit their applicability in TBI. Methods: We designed a new-KD with a fat to carbohydrate plus protein ratio of 2:1, containing medium chain triglycerides (MCT), docosahexaenoic acid (DHA), low glycaemic index carbohydrates, fibres and the ketogenic amino acid leucine, and evaluated its neuroprotective potential in adult TBI. Adult male C57BL6 mice were injured by controlled cortical impact (CCI) and assessed for 70 days, during which they received a control diet or the new-KD. Results: The new-KD, that markedly increased plasma Beta-hydroxybutyrate (ß-HB), significantly attenuated sensorimotor deficits and corrected spatial memory deficit. The lesion size, perilesional inflammation and oxidation were markedly reduced. Oligodendrocyte loss appeared to be significantly reduced. TBI activated the mTOR pathway and the new-KD enhanced this increase and increased histone acetylation and methylation. Conclusion: The behavioural improvement and tissue protection provide proof of principle that this new formulation has therapeutic potential in adult TBI.

Sensory neuronopathies: A case series and literature review.

Sensory neuronopathies are heterogeneous disorders of dorsal root ganglia. The clinical and laboratory features in a single-centre series, including response to treatment and outcome have been described. They retrospectively included 54 patients meeting Camdessanché et al (2009) criteria for sensory neuronopathy. The patients were classified according to their likely aetiology and analysed their demographic, clinical, neurophysiological, histological and spinal MRI features. The outcome with the modified Rankin Scale (mRS) was evaluated, and the response to treatment was assessed. About 54 patients were included (18 male; median age 54.5 years). The most common initial symptoms were hypoaesthesia, paraesthesia, ataxia and pain. Half of patients had a slow onset, greater than 12 months before seeing a neurologist. The aetiology as possibly inflammatory (meaning nonspecific laboratory evidence of immune abnormality) in 18 patients (33%), paraneoplastic 8 (15%), autoimmune 7 (13%) and idiopathic 6 (11%) was classified. About 31 patients received immune therapy of which 11 (35%) improved or stabilised. Corticosteroids were the most used treatment (24 patients) and cyclophosphamide had the highest response rate (3/6, 50%). At the final follow up (median 24 months) 67% had mRS ≥3 and 46% mRS ≥4, including 15% who died. Worse outcome was associated with generalised areflexia and pseudoathetosis by logistic regression, and with motor involvement and raised CSF protein by univariate analysis. Sensory neuronopathies caused severe disability, especially in patients with generalised areflexia and pseudoathetosis. Of those without an obvious cause, most had some evidence of dysimmunity. Some patients had a positive response to immunotherapy, but rarely enough to improve disability much.

Innocuous pressure sensation requires A-type afferents but not functional ΡΙΕΖΟ2 channels in humans.

The sensation of pressure allows us to feel sustained compression and body strain. While our understanding of cutaneous touch has grown significantly in recent years, how deep tissue sensations are detected remains less clear. Here, we use quantitative sensory evaluations of patients with rare sensory disorders, as well as nerve blocks in typical individuals, to probe the neural and genetic mechanisms for detecting non-painful pressure. We show that the ability to perceive innocuous pressures is lost when myelinated fiber function is experimentally blocked in healthy volunteers and that two patients lacking Aß fibers are strikingly unable to feel innocuous pressures at all. We find that seven individuals with inherited mutations in the mechanoreceptor PIEZO2 gene, who have major deficits in touch and proprioception, are nearly as good at sensing pressure as healthy control subjects. Together, these data support a role for Aß afferents in pressure sensation and suggest the existence of an unknown molecular pathway for its detection.

An investigation of the effect of the lower extremity sensation on gait in children with cerebral palsy.

BACKGROUND: Sensory disorders frequently accompany the motor disorders in children with cerebral palsy (CP). RESEARCH QUESTION: Do children with CP have sensory disturbances in their lower extremities? If there are sensory impairments, do these impairments affect gait? METHODS: In total, 45 children (18 females, 27 males) in an age range between 5 and 18 years were included in the study: 15 typically developing children, 15 unilaterally affected children with cerebral palsy, and 15 bilaterally affected children with cerebral palsy. They could walk independently at the levels of I or II according to the gross motor function classification. After the demographic data of the children were recorded, their tactile sense, vibration sense, two-point discrimination, and proprioception were evaluated, and the Edinburgh Visual Gait Score (EVGS) was used for gait assessment. RESULTS: Failures were discovered in lower extremity tactile (p = 0.001), two-point discrimination (p = 0.001), and proprioceptive senses of the children with CP (p = 0.001), and the loss of tactile sense was found to be related to gait disorders (p = 0.02, r = 0.41). SIGNIFICANCE: There were deficiencies in the lower extremity senses, and deficiencies in the tactile sense negatively affected gait. Performing sensory assessments, which are considered to be fundamental for gait training in the rehabilitation of children with CP, and providing support for the lacking parameters in the intervention programs may create positive effects on gait.