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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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Traumatic brain injury is a leading cause of mortality and morbidity in the United States. Acute trauma to the brain triggers chronic secondary injury mechanisms that contribute to long-term neurological impairment. We have developed a single, unilateral contusion injury model of sensorimotor dysfunction in adult mice. By targeting a topographically defined neurological circuit with a mild impact, we are able to track sustained behavioral deficits in sensorimotor function in the absence of tissue cavitation or neuronal loss in the contused cortex of these mice. Stereological histopathology and multiplex enzyme-linked immunosorbent assay proteomic screening confirm contusion resulted in chronic gliosis and the robust expression of innate immune cytokines and monocyte attractant chemokines IL-1β, IL-5, IL-6, TNFα, CXCL1, CXCL2, CXCL10, CCL2, and CCL3 in the contused cortex. In contrast, the expression of neuroinflammatory proteins with adaptive immune functions was not significantly modulated by injury. Our data support widespread activation of innate but not adaptive immune responses, confirming an association between sensorimotor dysfunction with innate immune activation in the absence of tissue or neuronal loss in our mice., (Published 2020. This article is a U.S. Government work and is in the public domain in the USA.)

Background: There exist functional deficits in motor, sensory, and olfactory abilities in dementias. Measures of these deficits have been discussed as potential clinical markers., Objective: We measured the deficit of motor, sensory, and olfactory functions on both the left and right body side, to study potential body lateralizations., Methods: This IRB-approved study (N = 84) performed left/right clinical tests of gross motor (dynamometer test), sensory (Von Frey test), and olfactory (peppermint oil test) ability. The Mini-Mental Status Exam was administered to determine level of dementia; medical and laboratory data were collected., Results: Sensory and olfactory deficits lateralized to the left side of the body, while motor deficits lateralized to the right side. We found clinical correlates of motor lateralization: female, depression, MMSE <15, and diabetes. While clinical correlates of sensory lateralization: use of psychotherapeutic agent, age ≥85, MMSE <15, and male. Lastly, clinical correlates of olfactory lateralization: age <85, number of medications >10, and male., Conclusion: These lateralized deficits in body function can act as early clinical markers for improved diagnosis and treatment. Future research should identify correlates and corresponding therapies to strengthen at-risk areas.

Background: Neuronal and sensory toxicity of mercury (Hg) compounds has been largely investigated in humans/mammals with a focus on public health, while research in fish is less prolific and dispersed by different species. Well-established premises for mammals have been governing fish research, but some contradictory findings suggest that knowledge translation between these animal groups needs prudence [e.g. the relative higher neurotoxicity of methylmercury (MeHg) vs. inorganic Hg (iHg)]. Biochemical/physiological differences between the groups (e.g. higher brain regeneration in fish) may determine distinct patterns. This review undertakes the challenge of identifying sensitive cellular targets, Hg-driven biochemical/physiological vulnerabilities in fish, while discriminating specificities for Hg forms., Scope of Review: A functional neuroanatomical perspective was conceived, comprising: (i) Hg occurrence in the aquatic environment; (ii) toxicokinetics on central nervous system (CNS)/sensory organs; (iii) effects on neurotransmission; (iv) biochemical/physiological effects on CNS/sensory organs; (v) morpho-structural changes on CNS/sensory organs; (vi) behavioral effects. The literature was also analyzed to generate a multidimensional conceptualization translated into a Rubik's Cube where key factors/processes were proposed., Major Conclusions: Hg neurosensory toxicity was unequivocally demonstrated. Some correspondence with toxicity mechanisms described for mammals (mainly at biochemical level) was identified. Although the research has been dispersed by numerous fish species, 29 key factors/processes were pinpointed., General Significance: Future trends were identified and translated into 25 factors/processes to be addressed. Unveiling the neurosensory toxicity of Hg in fish has a major motivation of protecting ichtyopopulations and ecosystems, but can also provide fundamental knowledge to the field of human neurodevelopment., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Christianson syndrome (CS) is a recently described rare neurogenetic disorder presenting early in life with a broad range of neurological symptoms, including severe intellectual disability with nonverbal status, hyperactivity, epilepsy, and progressive ataxia due to cerebellar atrophy. CS is due to loss-of-function mutations in SLC9A6, encoding NHE6, a sodium-hydrogen exchanger involved in the regulation of early endosomal pH. Here we review what is currently known about the neuropathogenesis of CS, based on insights from experimental models, which to date have focused on mechanisms that affect the CNS, specifically the brain. In addition, parental reports of sensory disturbances in their children with CS, including an apparent insensitivity to pain, led us to explore sensory function and related neuropathology in Slc9a6 KO mice. We present new data showing sensory deficits in Slc9a6 KO mice, which had reduced behavioral responses to noxious thermal and mechanical stimuli (Hargreaves and Von Frey assays, respectively) compared to wild type (WT) littermates. Immunohistochemical and ultrastructural analysis of the spinal cord and peripheral nervous system revealed intracellular accumulation of the glycosphingolipid GM2 ganglioside in KO but not WT mice. This cellular storage phenotype was most abundant in neurons of lamina I-II of the dorsal horn, a major relay site in the processing of painful stimuli. Spinal cords of KO mice also exhibited changes in astroglial and microglial populations throughout the gray matter suggestive of a neuroinflammatory process. Our findings establish the Slc9a6 KO mouse as a relevant tool for studying the sensory deficits in CS, and highlight selective vulnerabilities in relevant cell populations that may contribute to this phenotype. How NHE6 loss of function leads to such a multifaceted neurological syndrome is still undefined, and it is likely that NHE6 is involved with many cellular processes critical to normal nervous system development and function. In addition, the sensory issues exhibited by Slc9a6 KO mice, in combination with our neuropathological findings, are consistent with NHE6 loss of function impacting the entire nervous system. Sensory dysfunction in intellectually disabled individuals is challenging to assess and may impair patient safety and quality of life. Further mechanistic studies of the neurological impairments underlying CS and other genetic intellectual disability disorders must also take into account mechanisms affecting broader nervous system function in order to understand the full range of associated disabilities., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Gaze-evoked nystagmus is not rare among those who have acute balance problem and may indicate a cerebellar dysfunction that is associated with a broad spectrum of disorders. The aim of this study is to analyze optokinetic response in those patients. Eleven males and 7 females (age range: 25-60, 42.5 [9.75]) with gaze-evoked nystagmus were analyzed with optokinetic test (Micromed Inc). Nystagmus was elicited by a stimulator light spot moving across the patient's visual field at a target speed of 30 degree/second. Ten age-matched healthy participants served as controls. The gain and slow-phase velocity difference in oculomotor response from left and right stimulus was compared in patients and the control participants. One-way analysis of variance test was used for multiple variance analysis of the groups. Statistical significance was set at P < .05. Slow-phase velocity of gaze-evoked nystagmus was ranging between 6 and 19 degree/second. The mean slow-phase velocity of gaze-evoked nystagmus to the right and left was 8.1 (3.81) and 6.8 (4.67) degree/second, respectively. Optokinetic gain was out of normal limits in 10 (55.5%) patients. Comparison of mean gain difference between the patients and the normal participants was statistically significant ( P = .025). No statistical difference was found in mean slow-phase velocity difference in optokinetic nystagmus between control participants and patients ( P > .05 [.099]). An acute-onset balance problem may be associated with dysfunction of separate populations of neurons in the brainstem and cerebellum even if there is no radiological neuropathy since gaze-evoked nystagmus is a sign of neural integrator dysfunction. Patients with gaze-evoked nystagmus and optokinetic abnormalities may have disruption of cerebellar pathways and should be followed closely.

Genomic technologies such as next-generation sequencing (NGS) are revolutionizing molecular diagnostics and clinical medicine. However, these approaches have proven inefficient at identifying pathogenic repeat expansions. Here, we apply a collection of bioinformatics tools that can be utilized to identify either known or novel expanded repeat sequences in NGS data. We performed genetic studies of a cohort of 35 individuals from 22 families with a clinical diagnosis of cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS). Analysis of whole-genome sequence (WGS) data with five independent algorithms identified a recessively inherited intronic repeat expansion [(AAGGG) exp ] in the gene encoding Replication Factor C1 (RFC1). This motif, not reported in the reference sequence, localized to an Alu element and replaced the reference (AAAAG) 11 short tandem repeat. Genetic analyses confirmed the pathogenic expansion in 18 of 22 CANVAS-affected families and identified a core ancestral haplotype, estimated to have arisen in Europe more than twenty-five thousand years ago. WGS of the four RFC1-negative CANVAS-affected families identified plausible variants in three, with genomic re-diagnosis of SCA3, spastic ataxia of the Charlevoix-Saguenay type, and SCA45. This study identified the genetic basis of CANVAS and demonstrated that these improved bioinformatics tools increase the diagnostic utility of WGS to determine the genetic basis of a heterogeneous group of clinically overlapping neurogenetic disorders., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: We investigated the imaging counterpart of two functional domains (ocular motor dysfunction and postural instability) in progressive supranuclear palsy (PSP) patients classified according to the new clinical diagnostic criteria., Methods: Forty-eight patients with probable PSP-Richardson's syndrome (PSP-RS), 30 with probable PSP-parkinsonism (PSP-P), 37 with Parkinson's disease (PD), and 38 controls were enrolled. For each functional domain, PSP patients were stratified by two certainty levels: vertical supranuclear gaze palsy (O1) and slowness of vertical saccades (O2) for ocular motor dysfunction; early unprovoked falls and tendency to fall on the pull-test for postural instability. Voxel-based morphometry (VBM), whole-brain fractional anisotropy (FA) and MR planimetric measurements were analysed and compared across patient groups., Results: O1 was present in 64%, and O2 in 36% of all PSP patients. All PSP-RS patients showed early unprovoked falls. TBSS whole-brain analysis revealed that superior cerebellar peduncles (SCPs) were the only structures with significantly lower FA values in PSP-RS compared with PSP-P patients. PSP/O1 patients had lower FA values in midbrain than PSP/O2 patients. By contrast, VBM revealed no differences in grey matter volume between PSP patient groups. MR Planimetric measurements confirmed atrophy of midbrain and SCPs, in line with DTI findings., Conclusions: Our study demonstrates that SCPs were significantly more damaged in patients with PSP-RS in comparison with PSP-P patients, thus suggesting the role of SCPs in developing postural instability. Midbrain damage was less severe in O2 than in O1 patients, suggesting that the degree of vertical ocular dysfunction reflects the severity of midbrain atrophy., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Postural control requires the sensory integration of visual, vestibular, and proprioceptive signals. In the absence of vision, either by blindfolding or in blind individuals, balance performance is typically poorer than with sight. Previous research has suggested that despite showing compensatory vestibular and proprioceptive processing during upright standing, balance performance in blind individuals is overall lower than in sighted controls with eyes open. The present study tested whether balance training, which places demands on vestibular and proprioceptive self-motion perception, improves balance performance in blind adults, and whether we find similar structural correlates in cortical and subcortical brain areas as have been reported in sighted individuals. Fourteen congenitally or late blind adults were randomly assigned to either a balance or a relaxation group and exercised twice a week for 12 weeks. Assessments prior to and after training included balance tests and the acquisition of T1-weighted MRI images. The blind balance group significantly improved in dynamic, static, and functional balance performance compared to the blind relaxation group. The balance performance improvement did not differ from that of age- and gender matched sighted adults after balance training. Cortical thickness increased in the left parahippocampus and decreased in the inferior insula bilaterally in the blind balance group compared to the blind relaxation group. Thickness decreases in the insula were related to improved static and functional balance. Gray matter volume was reduced in the left hippocampus proper and increased in the right subiculum in the blind balance group. The present data suggest that impaired balance performance in blind adults can be significantly improved by a training inducing plasticity in brain regions associated with vestibular and proprioceptive self-motion processing., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aim: Our aim was to characterize the sensory processing outcome following neonatal arterial ischemic stroke (NAIS) and identify neuroanatomical correlates of abnormal sensory processing., Method: We evaluated children with NAIS longitudinally at 12 months, 18 months, and/or 30 months in areas of cognitive, motor, and language development. We gathered sensory processing data using the Sensory Profile-2 Caregiver Questionnaire. These data were analyzed against early magnetic resonance imaging using a voxel-based approach., Results: Eighteen children (10 males, 8 females) with NAIS were evaluated longitudinally, of which six exhibited atypical sensory processing. Children with sensory processing deficits had lower overall developmental scores in motor, cognitive, and language domains. Neuroanatomical correlates were identified in the posterior periventricular white matter extending superiorly into the supramarginal gyrus, and inferiorly into the fusiform and inferior temporal gyri., Interpretation: Our results provide new evidence that children with NAIS may experience difficulty processing sensory information, which is most likely associated with injuries in the posterior periventricular white matter, supramarginal gyrus, fusiform gyrus, and posterior thalamic radiation., What This Paper Adds: Atypical sensory processing is common in children with neonatal arterial ischemic stroke (NAIS). NAIS territories in sensory areas were correlated with atypical sensory processing behaviors. Children with NAIS may benefit from early interventions targeted toward sensory processing. Future research mapping NAIS injuries using early magnetic resonance imaging may predict long-term outcomes., (© 2018 Mac Keith Press.)

Hearing loss is one of the most prevalent sensory deficits worldwide and can result from the death of mechanosensory hair cells that transduce auditory signals in the cochlea. The mammalian cochlea lacks the capacity to regenerate these hair cells once damaged, and currently there are no biological therapies for hearing loss. Understanding the signaling pathways responsible for hair cell development can inform regenerative strategies and identify targets for treating hearing loss. The canonical Wnt and Notch pathways are critical for cochlear development; they converge on several key molecules, such as Atoh1, to regulate prosensory specification, proliferation, hair cell differentiation, and cellular organization. Much work has focused on Wnt and Notch modulation in the neonatal mouse cochlea, where they can promote hair cell regeneration. However, this regenerative response is limited in the adult cochlea and this might be attributed to age-dependent epigenetic modifications. Indeed, the epigenetic status at key gene loci undergoes dynamic changes during cochlear development, maturation, and aging. Therefore, strategies to improve regenerative success in the adult cochlea might require the modulation of Wnt, Notch, or other pathways, as well as targeted epigenetic modifications to alter the activity of key genes critical for supporting cell proliferation or transdifferentiation., (Copyright © 2019 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Postural instability gait disorder is a motor subtype of Parkinson disease associated with predominant gait dysfunction. We investigated the periventricular white matter comprising longitudinal, thalamic, and callosal fibers using diffusion tensor MR Imaging and examined clinical correlates in a cohort of patients with Parkinson disease and postural instability gait disorder and healthy controls., Materials and Methods: All subjects underwent the Tinetti Gait and Balance Assessment and brain MR imaging. The DTI indices (fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity) from ROIs dropped over the superior and inferior longitudinal fasciculi, inferior fronto-occipital fasciculus, anterior thalamic radiation, anterior and posterior limbs of the internal capsule, and the genu and body of corpus callosum were evaluated., Results: Our findings showed that the superior longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, anterior thalamic radiation, genu of the corpus callosum, and body of the corpus callosum are more affected in postural instability gait disorder than in those with Parkinson disease or healthy controls, with more group differences among the longitudinal fibers. Only the callosal fibers differentiated the postural instability gait disorder and Parkinson disease groups. DTI measures in the superior longitudinal fasciculus, frontostriatal fibers (anterior thalamic radiation, anterior limb of the internal capsule), and genu of the corpus callosum fibers correlated with clinical gait severity., Conclusions: Findings from this case-control cohort lend further evidence to the role of extranigral pathology and, specifically, the periventricular fibers in the pathophysiology of postural instability gait disorder., (© 2019 by American Journal of Neuroradiology.)

Background: Leprosy can be considered to be the most common peripheral neuropathy of infectious etiology and constitutes a public health problem. The standard routine examination for assessing sensory impairment in leprosy neuropathy basically evaluates hands, feet and eyes. However, evaluation of facial cutaneous sensation is not routinely performed., Objectives: The aim of this study was to evaluate facial cutaneous sensation in patients with different clinical forms of leprosy and compare the findings with those from healthy individuals., Methodology: 19 healthy controls and 71 leprosy patients who were being treated at a national reference center for leprosy in Brazil underwent facial sensation assessment using the Semmes-Weinstein monofilament test. This test was applied over the facial areas corresponding to the ophthalmic, maxillary and mandibular distal branches of the trigeminal nerve., Results: The predominant clinical form in terms of changes to facial cutaneous sensation was lepromatous leprosy (LL), followed by the borderline-borderline (BB), and borderline-lepromatous (BL) forms, in comparison with healthy individuals. The distal branches most affected were the zygomatic (28.2%; 20/71), buccal (23.9%; 17/71) and nasal (22.5%; 16/71). There was asymmetrical sensory impairment of the face in 62.5% (20/32) of the cases., Conclusion: The face is just as impaired in leprosy as are the feet, hands and eyes, but facial impairment is underdiagnosed. Our evaluation on the different sensory branches and evidence of asymmetrical impairment of the face confirm the classically described pattern of leprosy neuropathy, i.e. consisting of asymmetrical and predominantly sensory peripheral neuropathy., Competing Interests: The authors have declared that no competing interests exist.

Activation of nicotinic acetylcholine receptors (nAChRs) enhances sensory-cognitive function in human subjects and animal models, yet the neural mechanisms are not fully understood. This review summarizes recent studies on nicotinic regulation of neural processing in the cerebral cortex that point to potential mechanisms underlying enhanced cognitive function. Studies from our laboratory focus on nicotinic regulation of auditory cortex and implications for auditory-cognitive processing, but relevant emerging insights from multiple brain regions are discussed. Although the major contributions of the predominant nAChRs containing α7 (homomeric receptors) or α4 and β2 (heteromeric) subunits are well recognized, recent results point to additional, potentially critical contributions from α2 subunits that are relatively sparse in cortex. Ongoing studies aim to elucidate the specific contributions to cognitive and cortical function of diverse nAChRs., Implications: This review highlights the therapeutic potential of activating nAChRs in the cerebral cortex to enhance cognitive function. Future work also must determine the contributions of relatively rare but important nAChR subtypes, potentially to develop more selective treatments for cognitive deficits., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To examine whether hypoesthesia and chronic pain are related in patients with MS., Methods: Sixty-seven MS patients with pain and 80 persons without MS were included. Sensory functioning was tested by bedside neurological examination. Touch, joint position (dorsal column-medial lemniscus pathway), temperature sense, and pain (spinothalamic tract) were tested. Pain intensity was measured by the Colored Analogue Scale (CAS Intensity) and the Faces Pain Scale (FPS); pain affect was also measured by CAS Affect and Number of Words Chosen-Affective (NWC-A). Mood was assessed with the SCL-90 anxiety and depression subscales and the Beck Depression Inventory (BDI)., Results: A significant negative relationship was found between pain intensity and the function of the dorsal column-medial lemniscal pathway, but not with the spinothalamic tract., Conclusion: In addition to the already known relation between hyperesthesia and pain, hypoesthesia for touch and joint position also seems to be related to chronic pain in MS patients.

One in two survivors experience impairment in touch sensation after stroke. The nature of this impairment is likely associated with changes associated with the functional somatosensory network of the brain; however few studies have examined this. In particular, the impact of lesioned hemisphere has not been investigated. We examined resting state functional connectivity in 28 stroke survivors, 14 with left hemisphere and 14 with right hemisphere lesion, and 14 healthy controls. Contra-lesional hands showed significantly decreased touch discrimination. Whole brain functional connectivity (FC) data was extracted from four seed regions, i.e. primary (S1) and secondary (S2) somatosensory cortices in both hemispheres. Whole brain FC maps and Laterality Indices (LI) were calculated for subgroups. Inter-hemispheric FC was greater in healthy controls compared to the combined stroke cohort from the left S1 seed and bilateral S2 seeds. The left lesion subgroup showed decreased FC, relative to controls, from left ipsi-lesional S1 to contra-lesional S1 and to distributed temporal, occipital and parietal regions. In comparison, the right lesion group showed decreased connectivity from contra-lesional left S1 and bilateral S2 to ipsi-lesional parietal operculum (S2), and to occipital and temporal regions. The right lesion group also showed increased intra-hemispheric FC from ipsi-lesional right S1 to inferior parietal regions compared to controls. In comparison to the left lesion group, those with right lesion showed greater intra-hemispheric connectivity from left S1 to left parietal and occipital regions and from right S1 to right angular and parietal regions. Laterality Indices were significantly greater for stroke subgroups relative to matched controls for contra-lesional S1 (left lesion group) and contra-lesional S2 (both groups). We provide evidence of altered functional connectivity within the somatosensory network, across both hemispheres, and to other networks in stroke survivors with impaired touch sensation. Hemisphere of lesion was associated with different patterns of altered functional connectivity within the somatosensory network and with related function was associated with different patterns of altered functional connectivity within the somatosensory network and with related functional networks.

We elucidated whether verticality misperception is associated with the generation of Pisa syndrome (PS) in patients with Parkinson's disease (PD). To examine the heterogenous influence of verticality perception, we also identified the characteristics distinguishing between PD patients with PS who tilted toward the deviation of perceived verticality and those who did not. Subjective visual vertical (SVV) testing was performed in 54 PD patients with PS and 36 without PS to measure verticality perception. Other potential risk factors for PS were evaluated by assessing the asymmetry of motor symptoms, EMG activities of paraspinal muscles, bithermal caloric tests, back pain history, and Berg Balance Scale. Abnormal SVV (odds ratio (OR) 18.40, p = 0.006), postural imbalance (OR 0.71, p = 0.046), and unilateral EMG hyperactivity of paraspinal muscles (OR 39.62, p = 0.027) were independent contributors to PS. In subgroup analysis, EMG hyperactivity of paraspinal muscles contralateral to the leaning side and postural imbalance were associated with PD patients with PS who tilted toward the SVV deviation, whereas back pain was more frequent in those who did not. Verticality misperception is a potent risk factor for PS in PD and contributes differentially to PS depending on the congruence between its direction and PS direction, indicating distinct pathogenic roles.

Parkinson's disease (PD) is a circuit-level disorder with clinically-determined motor subtypes. Despite evidence suggesting each subtype may have different pathophysiology, few neuroimaging studies have examined levodopa-induced differences in neural activation between tremor dominant (TD) and postural instability/gait difficulty (PIGD) subtype patients during a motor task. The goal of this functional MRI (fMRI) study was to examine task-induced activation and connectivity in the cortico-striatal-thalamo-cortical motor circuit in healthy controls, TD patients, and PIGD patients before and after levodopa administration. Fourteen TD and 12 PIGD cognitively-intact patients and 21 age- and sex-matched healthy controls completed a right-hand, paced tapping fMRI paradigm. Collectively, PD patients off medication (OFF) showed hypoactivation of the motor cortex relative to healthy controls, even when controlling for performance. After levodopa intake, the PIGD patients had significantly increased activation in the left putamen compared with TD patients and healthy controls. Psychophysiological interaction analysis revealed that levodopa increased effective connectivity between the posterior putamen and other areas of the motor circuit during tapping in TD patients, but not in PIGD patients. This novel, levodopa-induced difference in the neural responses between PD motor subtypes may have significant implications for elucidating the mechanisms underlying the distinct phenotypic manifestations and enabling the classification of motor subtypes objectively using fMRI., (© 2017 Wiley Periodicals, Inc.)

Patients with schizophrenia show specific abnormalities in visual perception, and patients with bipolar disorder may have related perceptual deficits. During tasks that highlight perceptual dysfunction, patients with schizophrenia show abnormal activity in visual brain areas, including the lateral occipital complex (LOC) and early retinotopic cortex. It is unclear whether the anatomical structure of those visual areas is atypical in schizophrenia and bipolar disorder. In members of those two patient groups and healthy controls, we localized LOC and early retinotopic cortex individually for each participant using functional magnetic resonance imaging (MRI), then measured the thickness of those regions of interest using structural MRI scans. In both regions, patients with schizophrenia had the thinnest cortex, controls had the thickest cortex, and bipolar patients had intermediate cortical thickness. A control region, motor cortex, did not show this pattern of group differences. The thickness of each visual region of interest was significantly correlated with performance on a visual object masking task, but only in schizophrenia patients. These findings suggest an anatomical substrate for visual processing abnormalities that have been found with both neural and behavioral measures in schizophrenia and other severe mental illnesses., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Sporadic Alzheimer's disease (AD) is a devastating neurodegenerative disorder. It is essential to unravel its etiology and pathogenesis. This should enable us to study the presymptomatic stages of the disease and to analyze and reverse the antemortem behavioral, memory, and cognitive dysfunction. Prima facie, an ongoing chronic vulnerability involving neural insult may lead normal elderly to mild cognitive impairment (MCI) and then to AD. Development of effective preventive and therapeutic strategies to thwart the disease pathology obviously requires a thorough delineation of underlying disruptive neuropathological processes. Our sensory capacity for touch, smell, taste, hearing, and vision declines with advancing age. Declines in different sensory attributes are considered here to be the primary "first-tier pathologies." Olfactory loss is among the first clinical signs of neurodegenerative diseases including AD and Parkinson's disease (PD). Sensory dysfunction in the aged promotes pathological disturbances in the locus coeruleus, basal forebrain, entorhinal cortex, hippocampus, and several key areas of neocortex and brainstem. Hence, sensory dysfunction is the pivotal factor that may upregulate cognitive and memory dysfunction. The age-related constellation of comorbid pathological factors may include apolipoprotein E (APOE) genotype, obesity, diabetes, hypertension, alcohol abuse, head trauma, and obstructive sleep apnea. The concepts and trajectories delineated here are the dynamic pillars of the current hypothesis presented-it postulates that the sensory decline, in conjunction with the above pathologies, is crucial in triggering neurodegeneration and promoting cognitive/memory dysfunction in aging and AD. The application of this thesis can be important in formulating new multifactorial preventive and treatment strategies (suggested here) in order to attenuate cognitive and memory decline and ameliorate pathological dysfunction in aging, MCI, and AD.

Background: Sensory ganglionopathy (SG) is characterised by asymmetrical sensory fibre degeneration, with the primary pathology occurring at the level of the dorsal root ganglion. It is seen in the context of autoimmune, paraneoplastic, and degenerative disorders. There is limited literature examining the electrophysiological correlate of the trigeminal ganglion and associated pathways, the blink reflex (BR), in cases of SG. Previous work has suggested that the BR is preserved in cases of SG associated with paraneoplasia., Methods: The local clinical neurophysiology database was searched for patients diagnosed with SG from peripheral nerve conduction studies in whom the BR was performed. Twenty-six patients were included in the final analysis., Results: Sjögren's syndrome constituted the most common SG aetiology (8/26), followed by idiopathic cases (7/26) and paraneoplasia (5/26). BR abnormalities were seen in 9 of the 26 patients (34.6%) across all aetiologies. No patients reported sensory disturbance in the distribution of the trigeminal nerve, indicating that the changes noted are subclinical. Three patients showed abnormality of the R1 response; in the remaining six patients, only R2 responses were affected., Conclusions: Subclinical abnormalities of both R1 and R2 can be seen in the context of SG of varying aetiologies, including paraneoplasia. Performing the BR in patients with suspected of having SG may be helpful in providing additional evidence of patchy sensory fibre involvement that is characteristic of the disease.

Many patients with traumatic brain injury (TBI) suffer from postural control impairments that can profoundly affect daily life. The cerebellum and brain stem are crucial for the neural control of posture and have been shown to be vulnerable to primary and secondary structural consequences of TBI. The aim of this study was to investigate whether morphometric differences in the brain stem and cerebellum can account for impairments in static and dynamic postural control in TBI. TBI patients (n = 18) and healthy controls (n = 30) completed three challenging postural control tasks on the EquiTest® system (Neurocom). Infratentorial grey matter (GM) and white matter (WM) volumes were analyzed with cerebellum-optimized voxel-based morphometry using the spatially unbiased infratentorial toolbox. Volume loss in TBI patients was revealed in global cerebellar GM, global infratentorial WM, middle cerebellar peduncles, pons and midbrain. In the TBI group and across both groups, lower postural control performance was associated with reduced GM volume in the vermal/paravermal regions of lobules I-IV, V and VI. Moreover, across all participants, worse postural control performance was associated with lower WM volume in the pons, medulla, midbrain, superior and middle cerebellar peduncles and cerebellum. This is the first study in TBI patients to demonstrate an association between postural impairments and reduced volume in specific infratentorial brain areas. Volumetric measures of the brain stem and cerebellum may be valuable prognostic markers of the chronic neural pathology, which complicates rehabilitation of postural control in TBI., (© 2015 Wiley Periodicals, Inc.)

Optimal behavior relies on the combination of inputs from multiple senses through complex interactions within neocortical networks. The ontogeny of this multisensory interplay is still unknown. Here, we identify critical factors that control the development of visual-tactile processing by combining in vivo electrophysiology with anatomical/functional assessment of cortico-cortical communication and behavioral investigation of pigmented rats. We demonstrate that the transient reduction of unimodal (tactile) inputs during a short period of neonatal development prior to the first cross-modal experience affects feed-forward subcortico-cortical interactions by attenuating the cross-modal enhancement of evoked responses in the adult primary somatosensory cortex. Moreover, the neonatal manipulation alters cortico-cortical interactions by decreasing the cross-modal synchrony and directionality in line with the sparsification of direct projections between primary somatosensory and visual cortices. At the behavioral level, these functional and structural deficits resulted in lower cross-modal matching abilities. Thus, neonatal unimodal experience during defined developmental stages is necessary for setting up the neuronal networks of multisensory processing.

Our primary goal was to evaluate the behavioral and histological outcome of fluid percussion injury (FPI) and cortical contusion injury (CCI) to the sensorimotor cortex (SMC). The SMC has been used to evaluate neuroplasticity following CCI, but has not been extensively examined with FPI. In both the CCI and FPI models, a mechanical force of 4mm in diameter was applied over the SMC, allowing for a direct comparison to measure the relative rates of histology and recovery of function in these models. Gross behavioral deficits were found on the sensory task (tactile adhesive removal task) and multiple motor assessments (forelimb asymmetry task, forelimb placing task, and rotorod). These sensorimotor deficits occurred in the absence of cognitive deficits in the water maze. The CCI model creates focal damage with a localized injury wheras the FPI model creates a more diffuse injury causing widespread damage. Both behavioral and histological deficits ensued following both models of injury to the SMC. The neuroplastic changes and ease at which damage to this area can be measured behaviorally make this an excellent location to assess traumatic brain injury (TBI) treatments. No injury model can completely mimic the full spectrum of human TBI and any potential treatments should be validated across both focal and diffuse injury models. Both of these injury models to the SMC produce severe and enduring behavioral deficits, which are ideal for evaluating treatment options., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: In patients with subacute spinal cord injury (SCI), the motor system undergoes progressive structural changes rostral to the lesion, which are associated with motor outcome. The extent to which the sensory system is affected and how this relates to sensory outcome are uncertain., Methods: Changes in the sensory system were prospectively followed by applying a comprehensive magnetic resonance imaging (MRI) protocol to 14 patients with subacute traumatic SCI at baseline, 2 months, 6 months, and 12 months after injury, combined with a full neurological examination and comprehensive pain assessment. Eighteen controls underwent the same MRI protocol. T1-weighted volumes, myelin-sensitive magnetization transfer saturation (MT), and longitudinal relaxation rate (R1) mapping provided data on spinal cord and brain morphometry and microstructure. Regression analysis assessed the relationship between MRI readouts and sensory outcomes., Results: At 12 months from baseline, sensory scores were unchanged and below-level neuropathic pain became prominent. Compared with controls, patients showed progressive degenerative changes in cervical cord and brain morphometry across the sensory system. At 12 months, MT and R1 were reduced in areas of structural decline. Sensory scores at 12 months correlated with rate of change in cord area and brain volume and decreased MT in the spinal cord at 12 months., Interpretation: This study has demonstrated progressive atrophic and microstructural changes across the sensory system with a close relation to sensory outcome. Structural MRI protocols remote from the site of lesion provide new insights into neuronal degeneration underpinning sensory disturbance and have potential as responsive biomarkers of rehabilitation and treatment interventions., (© 2015 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.)

Very little is known about pain processing in sickle cell disease (SCD). We examined the mechanical and thermal sensory patterns in children with SCD. Children ages 10 to 17 years (n = 48; mean 13.7 ± 2.0 y; 22 females) participated in quantitative sensory testing (QST) procedures and completed a quality of life (PedsQL) and anxiety and depression scale (RCADS). Thirteen children showed evidence of abnormal pain processing, indicated by decreased sensitivity to heat or cold sensations (hypoesthesia), and pain experienced with nonpainful stimuli (allodynia). Pain ratings associated with cold and warm sensations were significantly higher in the subgroup with abnormal QST compared with the 35 SCD children with normal QST (P = 0.01 and P < 0.0001, respectively). The presence of hypoesthesia and allodynia in children with SCD may represent abnormal changes in the peripheral and central nervous system. Clinicians need to be aware that sickle cell pain may not only be inflammatory or ischemic secondary to vasoocclusion and hypoxia, but may also be neuropathic secondary to nerve injury or nerve dysfunction. Neuropathic pain in SCD may be the result of tissue damage after vaso-occlusion in neural tissues, whether peripherally or centrally. Future studies are needed to determine the presence of neuropathic pain in children with SCD.

Human bipedal gait requires supraspinal control and gait is consequently severely impaired in most persons with spinal cord injury (SCI). Little is known of the contribution of lesion of specific descending pathways to the clinical manifestations of gait deficits. Here, we assessed transmission in descending pathways using imaging and electrophysiological techniques and correlated them with clinical measures of impaired gait in persons with SCI. Twenty-five persons with SCI participated in the study. Functional assessment of gait included the Walking Index for Spinal Cord Injury (WISCI), the Timed-Up and Go (TUG), the 6-Min Walking Test (6MWT), and the maximal treadmill gait speed. Balance was evaluated clinically by the Berg Balance Scale (BBS). The amplitude of tibialis anterior (TA) motor-evoked potentials (MEPs) at rest elicited by transcranial magnetic stimulation as a measure of corticospinal transmission showed a moderately good correlation with all clinical measures (r(2)~0.5), whereas the latency of the MEPs showed less good correlation (r(2)~0.35). Interestingly, the MEP amplitude was correlated to atrophy in the ventrolateral rather than the dorsolateral section of the spinal cord where the main part of the corticospinal tract is located. TA intramuscular coherence in the beta and gamma frequency range has been suggested to reflect corticospinal transmission and was, consistent with this, found to be correlated to atrophy in the dorsolateral and ventrolateral sections of the spinal cord. Coherence was found to correlate to all clinical measures to the same extent as the MEP amplitude. The latency and duration of medium-latency responses in the soleus muscle to galvanic stimulation as measures of vestibulospinal transmission showed very good correlation to BBS (r(2)=-0.8) and moderately good correlation to the assessments of gait function (r(2)~0.4). 6MWT and gait speed were correlated to atrophy of the lateral sections of the spinal cord bilaterally, whereas BBS was correlated to atrophy of both lateral and ventral sections of the spinal cord. No significant correlation was observed between the electrophysiological tests of corticospinal and vestibulospinal transmission. Combination of different electrophysiological and anatomical measures using best subset regression analysis revealed improved prediction of gait ability, especially in the case of WISCI. These findings illustrate that lesion of corticospinal and vestibulospinal pathways makes different contributions to impaired gait ability and balance following SCI and that no single electrophysiological or anatomical measure provide an optimal prediction of clinical gait and balance disability. We suggest using a combination of anatomical and electrophysiological measures when evaluating spinal cord integrity following SCI., (© 2015 Elsevier B.V. All rights reserved.)

The isolated body lateropulsion has been well recognized in caudal lateral medullary infarction and postulated to result from the involvement of ipsilateral dorsal spinocerebellar tract which is known to convey proprioception of trunk and legs. However, there has been no case accompanied by the tilt of the subjective visual vertical in caudal lateral medullary infarction. Recently, it has been suggested that a lesion in the ipsilateral graviceptive vestibulothalamic pathway can lead to alteration of subjective visual vertical without ocular tilt reaction in various brainstem lesions. Here we describe two cases of caudal lateral medullary infarction with ipsilesional body lateropulsion and subjective visual vertical tilt but without limb ataxia or ocular tilt reaction. It could be hypothesized that the ascending graviceptive information from the spinal cord may run adjacent to the dorsal spinocerebellar tract or perception of the visual vertical can be influenced by ascending spinal proprioception.

Postural abnormalities such as postural deviations affect nearly all patients with advanced Parkinson's disease and represent an important source of disability. Although their existence has long been known, their management remains a challenge as they respond poorly to medication, brain surgery, or physiotherapy. Improving management strategies will require better understanding of the mechanisms underlying such postural deformities. In this review on the pathophysiology of Pisa syndrome, we examine the data supporting the central and peripheral hypotheses that attempt to explain these lateral trunk deviations. Although the pathophysiology is very probably multifactorial, the bulk of the data supports central, rather than peripheral, hypotheses. The central hypotheses that are best supported by both animal studies and clinical data include asymmetry of basal ganglia output and abnormalities in the central integration of sensory information. Further studies are needed to elucidate the pathophysiology underlying Pisa syndrome., (© 2014 International Parkinson and Movement Disorder Society.)

Objective: To elucidate the neuropathology in cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS), a novel cerebellar ataxia comprised of the triad of cerebellar impairment, bilateral vestibular hypofunction, and a peripheral sensory deficit., Method: Brain and spinal neuropathology in 2 patients with CANVAS, together with brain and otopathology in another patient with CANVAS, were examined postmortem., Results: Spinal cord pathology demonstrated a marked dorsal root ganglionopathy with secondary tract degeneration. Cerebellar pathology showed loss of Purkinje cells, predominantly in the vermis., Conclusion: The likely underlying sensory pathology in CANVAS is loss of neurons from the dorsal root and V, VII, and VIII cranial nerve ganglia-in other words, it is a "neuronopathy" rather than a "neuropathy." Clinically, CANVAS is a differential diagnosis for both spinocerebellar ataxia type 3 (or Machado-Joseph disease) and Friedreich ataxia. In addition, there are 6 sets of sibling pairs, implying that CANVAS is likely to be a late-onset recessive or autosomal dominant with reduced penetrance disorder, and identification of the culprit gene is currently a target of investigation.

Migraine is a cyclic disorder, in which functional and morphological brain changes fluctuate over time, culminating periodically in an attack. In the migrainous brain, temporal processing of external stimuli and sequential recruitment of neuronal networks are often dysfunctional. These changes reflect complex CNS dysfunction patterns. Assessment of multimodal evoked potentials and nociceptive reflex responses can reveal altered patterns of the brain's electrophysiological activity, thereby aiding our understanding of the pathophysiology of migraine. In this Review, we summarize the most important findings on temporal processing of evoked and reflex responses in migraine. Considering these data, we propose that thalamocortical dysrhythmia may be responsible for the altered synchronicity in migraine. To test this hypothesis in future research, electrophysiological recordings should be combined with neuroimaging studies so that the temporal patterns of sensory processing in patients with migraine can be correlated with the accompanying anatomical and functional changes.

A 64-year-old obese man developed hypesthesia in the left arm and leg. Neurological examination revealed decreased senses of pain, touch, and temperature in the left face, arm, trunk, and leg. Remaining functions were normal. Electrocardiogram showed atrial fibrillation. Somatosensory-evoked potentials using the stimulation in the median nerve were normal on both sides. Brain magnetic resonance imaging revealed acute infarction in the right parietal operculum and insula. There were no pathognomonic lesions in the postcentral gyrus, the thalamus, or the brain stem. Cardioembolic operculo-insular infarction was diagnosed. Diffusion tensor tractography map displayed the thalamocortical projections to the primary and the secondary somatosensory cortex (S2). These radiological findings supported that the operculo-insular lesion could disrupt the thalamo-S2 pathway. Thus, the thalamocortical disconnection between the thalamus to the S2 could cause superficial hemisensory dysfunction in the present patient., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

As many human sensory and cognitive diseases are caused by irreversible damage or loss of certain types of neurons, methodologies aimed at replacement of lost neurons are key to restore lost sensation. Recent advances in generation of ear-cell progenitors, optic-cup structures and cortical neurons from human embryonic stem cells and induced pluripotent stem cells provide versatile tools for modeling human diseases and developing cells for replacement therapies.

Introduction: Sensory neuronopathy (SNN) is a distinctive subtype of peripheral neuropathies, specifically targeting dorsal root ganglion (DRG). We utilized MRI to demonstrate the imaging characteristics of DRG, spinal cord (SC), and brachial plexus at C7 level in SNN., Methods: We attempted multiple-echo data image combination (MEDIC) and turbo inversion recovery magnitude (TIRM) methods in nine patients with sensory neuronopathy and compared with those in 16 disease controls and 20 healthy volunteers. All participants underwent MRI for the measurement of DRG, posterior column (PC), lateral column, and spinal cord area (SCA) at C7 level. DRG diameters were obtained through its largest cross section, standardized by dividing sagittal diameter of mid-C7 vertebral canal. We also made comparisons of standardized anteroposterior diameter (APD) and left-right diameters of SC and PC in these groups. Signal intensity and diameter of C7 spinal nerve were assessed on TIRM., Results: Compared to control groups, signal intensities of DRG and PC were higher in SNN patients when using MEDIC, but the standardized diameters were shorter in either DRG or PC. Abnormal PC signal intensities were identified in eight out of nine SNN patients (89 %) with MEDIC and five out of nine (56 %) with T2-weighted images. SCA, assessed with MEDIC, was smaller in SNN patients than in the other groups, with significant reduction of its standardized APD. C7 nerve root diameters, assessed with TIRM, were decreased in SNN patients., Conclusion: MEDIC and TIRM sequences demonstrate increased signal intensities and decreased area of DRG and PC, and decreased diameter of nerve roots in patients with SNN, which can play a significant role in early diagnosis.

The central nervous system (CNS)-based symptoms of Gulf War Illness (GWI) include motor dysfunction, anxiety, and cognitive impairment. Gulf War (GW) agents, such as pyridostigmine bromide (PB), permethrin (PER), N,N-diethyl-meta-toluamide (DEET), and stress, are among the contributory factors to the pathobiology of GWI. This study characterizes disturbances in phosphocholine-containing lipids that accompany neurobehavioral and neuropathological features associated with GW agent exposure. Exposed mice received PB orally, dermal application of PER and DEET and restraint stress daily for 28 days, while controls received vehicle during this period. Neurobehavioral studies included the rotarod, open field, and Morris water maze tests. Histopathological assessments included glial fibrillary acid protein, CD45, and Nissl staining. Liquid chromatography/mass spectrometry with source collision-induced dissociation in negative and positive ionization scanning modes was performed to characterize brain phosphatidylcholine (PC) and sphingomyelin (SM). A significant increase in ether containing PC (ePC34:0, ePC36:2, and ePC36:1) or long-chain fatty acid-containing PC (38:1, 40:4, 40:2) was observed in exposed mice compared with controls. Among differentially expressed PCs, levels of those with monounsaturated fatty acids were more affected than those with saturated and polyunsaturated fatty acids. Sensorimotor deficits and anxiety, together with an increase in astrocytosis, were observed in exposed mice compared with controls. These lipid changes suggest that alterations in peroxisomal pathways and stearoyl-CoA desaturase activity accompany neurobehavioral and neuropathological changes after GW agent exposure and represent possible treatment targets for the CNS symptoms of GWI.

Objectives: To report a case of multifocal fibrosclerosis with a nine-year follow up, and to discuss this disease's radiological appearance and management. The disease is a rare systemic disorder of unknown cause characterised by fibrous proliferation involving multiple anatomical sites., Case Report: A 50-year-old woman presented with histological findings characterised by similar inflammatory processes involving the meninges, pituitary gland, peritoneum, retroperitoneum and orbits, prompting a search for a common pathophysiology. A diagnosis of multifocal fibrosclerosis was postulated. Symptom improvement was noted after treatment with prednisone and azathioprine., Conclusion: This is the first documented case of involvement of the cochleovestibular nerve in a patient with multifocal fibrosclerosis. The rare association between fibrotic diseases and masses showing various clinical patterns should be kept in mind by otolaryngologists, and imaging performed to investigate for multifocal fibrosclerosis. However, diagnosis can only be confirmed with tissue biopsy and histopathological examination.

Many veterans chronically ill from the 1991 Gulf War exhibit symptoms of altered sensation, including chronic pain. In this study of 55 veterans of a Construction Battalion previously examined in 1995-1996 and 1997-1998, brain activation to innocuous and noxious heat stimuli was assessed in 2008-2009 with a quantitative sensory testing fMRI protocol in control veterans and groups representing three syndrome variants. Testing outside the scanner revealed no significant differences in warm detection or heat pain threshold among the four groups. In the fMRI study, Syndrome 1 and Syndrome 2, but not Syndrome 3, exhibited hypo-activation to innocuous heat and hyper-activation to noxious heat stimuli compared to controls. The results indicate abnormal central processing of sensory and painful stimuli in 2 of 3 variants of Gulf War illness and call for a more comprehensive study with a larger, representative sample of veterans., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: In order to clarify the laryngeal sensation of bulbar palsy patients, we studied the relationship between laryngopharyngeal sensation and brainstem lesion in patients with dysphagia caused by bulbar palsy., Methods: Fifteen patients with lateral medullary infarction and dysphagia were included in this study. We performed laryngeal sensory test using the flexible laryngoscope and probes method previously developed by Yaguchi et al. The test sites included the right and left tip of the laryngeal surface of the epiglottis and bilateral arytenoid regions. Lesion sites were identified by magnetic resonance imaging and classified horizontally according to Kim's classification. We also used the anatomical atlas Cytoarchitecture of the Human Brain Stem to determine whether the lesions included the nucleus solitarius and nucleus ambiguus., Results: Eight cases had normal sensation and 7 cases had decreased sensation of the affected side of the epiglottis and arytenoid region. The lesions of decreased laryngeal sensation group were classified horizontally as large type or dorsal type and included the nucleus solitarius. Decreased laryngeal sensation was significantly correlated with lesions that included the nucleus solitarius (Fisher exact test; P = .026)., Conclusions: This study clarifies that patients with dysphagia caused by bulbar palsy may present with laryngeal sensory impairment of the affected side and laryngopharyngeal movement disorder. The important finding is that damage to both the nucleus solitarius and ambiguus cause dysphagia accompanied by decreased laryngeal sensation and that the lesions are relatively extensive and affect the middle level of the dorsal medulla., (Copyright © 2012 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Cilia are highly specialized microtubule-based organelles that have pivotal roles in numerous biological processes, including transducing sensory signals. Defects in cilia biogenesis and transport cause pleiotropic human ciliopathies. Mutations in over 30 different genes can lead to cilia defects, and complex interactions exist among ciliopathy-associated proteins. Mutations of the centrosomal protein 290 kDa (CEP290) lead to distinct clinical manifestations, including Leber congenital amaurosis (LCA), a hereditary cause of blindness due to photoreceptor degeneration. Mice homozygous for a mutant Cep290 allele (Cep290rd16 mice) exhibit LCA-like early-onset retinal degeneration that is caused by an in-frame deletion in the CEP290 protein. Here, we show that the domain deleted in the protein encoded by the Cep290rd16 allele directly interacts with another ciliopathy protein, MKKS. MKKS mutations identified in patients with the ciliopathy Bardet-Biedl syndrome disrupted this interaction. In zebrafish embryos, combined subminimal knockdown of mkks and cep290 produced sensory defects in the eye and inner ear. Intriguingly, combinations of Cep290rd16 and Mkksko alleles in mice led to improved ciliogenesis and sensory functions compared with those of either mutant alone. We propose that altered association of CEP290 and MKKS affects the integrity of multiprotein complexes at the cilia transition zone and basal body. Amelioration of the sensory phenotypes caused by specific mutations in one protein by removal of an interacting domain/protein suggests a possible novel approach for treating human ciliopathies.

Unilateral stroke can lead to a disorder of postural balance that manifests as a pushing away toward the contralesional side. It is called "pusher syndrome" (PS). The aims of this study were first to assess the anatomical cortical regions that induce PS and second to clarify whether tilt of the subjective visual vertical (SVV)--a sign of vestibular otolith dysfunction--is associated with PS. Sixty-six patients with acute unilateral strokes (28 left-sided lesions, 38 right-sided lesions) were tested for PS, for tilts of the SVV, for hemineglect and for the anatomical lesion site by magnetic resonance imaging (MRI)-based voxelwise lesion-behavior mapping analysis. Our data indicated no significant voxels; however, there was a trend towards an association between lesions of the posterior part of the insula, the operculum and the superior temporal gyrus--key areas of the multisensory vestibular cortical network--and the extent of pushing in patients with right-sided lesions, whereas the rather anterior part of the insula, the operculum as well as the internal capsule reaching to the lateral thalamus seemed to be involved in PS in left-sided lesion patients. These data might point toward a link between the systems responsible for postural control and for processing vestibular otolith information. These findings indicate that vestibular information might be fundamental in right-sided lesion patients for maintaining body posture in space.

Introduction: Non-length-dependent small-fiber sensory neuropathy (NLD-SFSN) is not as well characterized as length-dependent small-fiber sensory neuropathy (LD-SFSN)., Methods: Sixty-three patients with NLD-SFSN were compared with 175 patients with LD-SFSN for their demographics and disease associations., Results: Age was younger in those with NLD-SFSN (45.5 ± 13.1 years) than in those with LD-SFSN (55.1 ± 11.4 years, P < 0.001). Forty-six of 63 (73.0%) patients were women in the NLD-SFSN group, whereas 84 of 175 (48.0%) were women in the LD-SFSN group (P < 0.001). Disease associations were identified in 26 of 63 (41.3%) patients with NLD-SFSN, including diabetes or prediabetes in 10 (15.9%), connective tissue diseases in 6 (9.5%), thyroid dysfunction in 4 (6.3%), sarcoidosis in 3 (4.8%), vitamin B(12) deficiency in 2 (3.2%), and paraproteinemia in 1 (1.6%). Immune-mediated conditions were present in 9 of 63 (14.3%) patients with NLD-SFSN and 6 of 175 (3.4%) patients with LD-SFSN (P = 0.012)., Conclusions: NLD-SFSN is more common in women, presents at a younger age, and is more likely to be associated with immune-mediated conditions than LD-SFSN., (Copyright © 2011 Wiley Periodicals, Inc.)