Disrupted Association of Sensory Neurons With Enveloping Satellite Glial Cells in Fragile X Mouse Model

Among most prevalent deficits in individuals with Fragile X syndrome (FXS) is hypersensitivity to sensory stimuli and somatosensory alterations. Whether dysfunction in peripheral sensory system contributes to these deficits remains poorly understood. Satellite glial cells (SGCs), which envelop sensory neuron soma, play critical roles in regulating neuronal function and excitability. The potential contributions of SGCs to sensory deficits in FXS remain unexplored. Here we found major structural defects in sensory neuron-SGC association in the dorsal root ganglia (DRG), manifested by aberrant covering of the neuron and gaps between SGCs and the neuron along their contact surface. Single-cell RNAseq analyses demonstrated transcriptional changes in both neurons and SGCs, indicative of defects in neuronal maturation and altered SGC vesicular secretion. We validated these changes using fluorescence microscopy, qPCR, and high-resolution transmission electron microscopy (TEM) in combination with computational analyses using deep learning networks. These results revealed a disrupted neuron-glia association at the structural and functional levels. Given the well-established role for SGCs in regulating sensory neuron function, altered neuron-glia association may contribute to sensory deficits in FXS.

Idiopathic intracranial hypertension leading to bilateral optic atrophy in a patient with recent COVID-19 infection: a case report

Neurologic complications are common in patients hospitalised with COVID-19 infection. Most common complications are myalgias, headaches, encephalopathy and dizziness. Uncommon complications are stroke, motor and sensory deficits, seizures, ataxia and movement disorders. Multiple neuro-ophthalmological manifestations have also been reported in association with COVID-19. These complications may be the result of a range of pathophysiological mechanisms like hypoxic neuronal injury during active COVID-19 infection, RAS dysfunction, immune dysfunction and direct injury by the virus etc throughout the course of the disease. Here we reported a case of neuro-ophthalmic complication of Idiopathic intracranial hypertension (IIH) followed by bilateral optic atrophy in a middle-aged man with recent COVID-19 infection. He presented to the emergency with complaints of headache, dizziness and sudden painless bilateral diminution of vision for 3 days. His fundus examination was suggestive of bilateral papilledema, his MRI brain was normal and opening pressure of CSF was raised on lumbar puncture. His MRV was normal, there was no evidence of CSVT. He was started on steroids and acetazolamide. His headache improved but there was no improvement in visual acuity. Repeat fundus showed pale disc and MRI orbit was suggestive of bilateral optic atrophy.

Safety and Efficacy of Postoperative Indwelling Popliteal Nerve Catheters for Outpatient Charcot-Marie-Tooth Surgery

Background: Outpatient surgical deformity correction for Charcot-Marie-Tooth (CMT) disease is limited by effective postoperative pain control. Our previous institutional protocol for foot and ankle surgery in this population included preoperative single-injection nerve blocks, but patients often experienced uncontrolled pain when the block wore off postoperative day 0 or 1, resulting in high opioid requirements and unplanned emergency department visits. The use of ultrasonography-guided continuous nerve catheters in CMT patients has not previously been studied. We aimed to prospectively investigate the safety and efficacy of ultrasonography-guided indwelling popliteal catheters in CMT patients undergoing outpatient foot deformity correction surgery. Methods: Twenty CMT patients, average 28 (range 13-53) years old, undergoing reconstructive surgery by a single foot and ankle attending surgeon were consented for preoperative ultrasonography-guided popliteal catheters. This series included 24 total outpatient procedures; 4 were staged bilateral. Indwelling popliteal catheters were maintained on discharge, providing continuous infusion until postoperative day (POD) 3, and then self-discontinued. Patients were prescribed oxycodone 5 mg (60-80 pills) as needed for breakthrough pain. Outcomes collected included daily pain scores (0-10), an opioid pill count on POD 14, and patient satisfaction ratings. Neurologic evaluation by 5-point 10g Semmes-Weinstein monofilament testing was performed preoperatively and on POD 14. Results: There were no observed catheter-site infections or hematomas. Nine of the patients had pre-existing sensory deficits involving at least 2 areas on the 5-point monofilament test. Postoperative testing showed these deficits were unchanged and there were no instances of new sensory deficits. Postoperative pain scores were typically low, with median values (interquartile ranges [IQRs]) of 3.5 (2.0-5.0) on POD 1, 2.5 (2.0-5.0) on POD 2, and 2.5 (1.0-3.75) on POD 3. At POD 14, pain was 1.0 (0-1.0). Patients consumed a median of 25 oxycodone pills (IQR 8-43) over 2 weeks, less than half the prescribed number. Patient satisfaction was high. All patients reported they would choose to have a nerve catheter again for a similar surgery. Conclusion: This cases series demonstrated that regional anesthesia using ultrasonography-guided indwelling popliteal catheters was safe and effective for pain control in CMT patients undergoing outpatient foot and ankle surgery. Opioid consumption was comparable to published rates following major bony procedures, and no patients required emergent treatment or hospital admission for uncontrolled pain. No new sensory deficits were detected and patients with underlying sensory deficits remained unchanged. Patients were highly satisfied. Level of Evidence: Level IV, case series.

Segmental Schwannomatosis in the Upper Extremity: A Case Report and Review of Literature

Schwannomas, the most frequently occurring benign tumors of the peripheral nerve sheath, generally remain as painless swellings for several years before diagnosis. Multiple schwannomas involving different nerves within the same extremity are rare. We report a rare case of a 61-year-old female who presented with multiple schwannomas in the palmar common and proper digital nerves, 15 years after the resection of a median nerve schwannoma within the same upper extremity. Using preestablished diagnostic criteria, she was diagnosed with segmental schwannomatosis. After careful surgical resection, biopsy confirmed the diagnosis and she recovered without neurological symptoms or limitations in the range of motion. Literature review revealed only four case series on segmental schwannomatosis, indicating its rarity. Postoperative sensory deficits are more likely in cases with multiple schwannomas in the common and proper digital nerves. We demonstrate that such complications can be avoided by meticulous dissection and separation of the tumors from the nerve fibers.

Clinical and Utilization Outcomes of Matched People With and Without HIV Aged 65+

The prevalence of age-standardized comorbidities is significantly elevated for PLWH across an array of cohorts. However, healthcare needs of older people living with (PLWH) and without (PWOH) HIV may be similar if they have similar geriatric conditions. PLWH and PWOH aged 65+ and eligible for Medicare from 7/1/2014-1/1/2015 were matched 1:1 on age, sex, race, and census region (n=7654). Cox regression assessed count of prevalent geriatric conditions (dementia, depression, falls, hip fracture, sensory deficits, osteoporosis, orthostatic hypotension, urinary incontinence, frailty, and polypharmacy), and risk for clinical or utilization outcomes (cancer, kidney disease, muscle wasting, hepatitis C, liver disease, myocardial infarction, stroke; hospitalization, nursing home and home health admission) during follow-up between 1/1/2015-12/31/2016. PLWH and PWOH are similar in count of geriatric conditions. Compared to those with none, those having 2+ geriatric conditions were similar across PLWH and PWOH in their risk of ≥1 clinical outcome (PLWH: HR 1.57 95% CI [1.29-1.90]; PWOH: HR 1.31 [1.02-1.67]), hospitalization (PLWH: HR 2.35 [1.96-2.83]; PWOH: HR 2.07 [1.65-2.60]), and home health admission (PLWH: HR 2.09 [1.58-2.76]; PWOH: HR 2.20 [1.55-3.12]). Having 2+ geriatric conditions, PWOH had 4.45 times the risk (95% CI 3.16-6.26) and PLWH had 2.88 times the risk (95% CI 2.18-3.81) of NH admission compared to no geriatric conditions. In this study, PLWH use nursing homes less than PWOH despite having a similar number of geriatric conditions and clinical outcomes. Further research to understand this apparent discrepancy will be critical to achieve equity in nursing home access.

Restoring Shank3 in the rostral brainstem of shank3ab−/− zebrafish autism models rescues sensory deficits

People with Phelan-McDermid Syndrome, caused by mutations in the SHANK3 gene, commonly exhibit reduced responses to sensory stimuli; yet the changes in brain-wide activity that link these symptoms to mutations in the shank3 gene remain unknown. Here we quantify movement in response to sudden darkness in larvae of two shank3 zebrafish mutant models and show that both models exhibit dampened responses to this stimulus. Using brain-wide activity mapping, we find that shank3−/− light-sensing brain regions show normal levels of activity while sensorimotor integration and motor regions are less active. Specifically restoring Shank3 function in a sensorimotor nucleus of the rostral brainstem enables the shank3−/− model to respond like wild-type. In sum, we find that reduced sensory responsiveness in shank3−/− models is associated with reduced activity in sensory processing brain regions and can be rescued by restoring Shank3 function in the rostral brainstem. These studies highlight the importance of Shank3 function in the rostral brainstem for integrating sensory inputs to generate behavioral adaptations to changing sensory stimuli.

Intramedullary Sclerosing Meningioma in Meningiomatosis: Case Report and Review of the Literature

Sclerosing meningioma is a rare histological variant of meningioma, first described in the literature by Davidson and Hope in 1989 as an invasive bulking mass consisted of whorling collagen bundles with a minimum percentage of meningothelial resembling cells [1]. The literature showed very rare cases of the intramedullary location of sclerosing meningiomas: in our opinion, it is mandatory to describe its clinical, surgical, histological and immunohistochemical features in order to reach the best final outcome. Sclerosing meningiomas are often misdiagnosed because of their invasive behaviour: it does require a correct diagnosis in order to prevent unnecessary postoperative treatment. Literature reports only 30 cases of sclerosing meningiomas and only 2 of them are intramedullary. We present the case of a cervical intramedullary sclerosing meningioma presenting with gait disturbances, sensory deficits, four extremities weakness and hypereflexia in a patient with the history of meningiomatosis.

Electroretinography and contrast sensitivity, complementary translational biomarkers of sensory deficits in the visual system of individuals with fragile X syndrome

Background Disturbances in sensory function are an important clinical feature of neurodevelopmental disorders such as fragile X syndrome (FXS). Evidence also directly connects sensory abnormalities with the clinical expression of behavioral impairments in individuals with FXS; thus, positioning sensory function as a potential clinical target for the development of new therapeutics. Using electroretinography (ERG) and contrast sensitivity (CS), we previously reported the presence of sensory deficits in the visual system of the Fmr1−/y genetic mouse model of FXS. The goals of the current study were two-folds: (1) to assess the feasibility of measuring ERG and CS as a biomarker of sensory deficits in individuals with FXS, and (2) to investigate whether the deficits revealed by ERG and CS in Fmr1−/y mice translate to humans with FXS. Methods Both ERG and CS were measured in a cohort of male individuals with FXS (n = 20, 18–45 years) and age-matched healthy controls (n = 20, 18–45 years). Under light-adapted conditions, and using both single flash and flicker (repeated train of flashes) stimulation protocols, retinal function was recorded from individual subjects using a portable, handheld, full-field flash ERG device (RETeval®, LKC Technologies Inc., Gaithersburg, MD, USA). CS was assessed in each subject using the LEA SYMBOLS® low-contrast test (Good-Lite, Elgin, IL, USA). Results Data recording was successfully completed for ERG and assessment of CS in most individuals from both cohorts demonstrating the feasibility of these methods for use in the FXS population. Similar to previously reported findings from the Fmr1−/y genetic mouse model, individuals with FXS were found to exhibit reduced b-wave and flicker amplitude in ERG and an impaired ability to discriminate contrasts compared to healthy controls. Conclusions This study demonstrates the feasibility of using ERG and CS for assessing visual deficits in FXS and establishes the translational validity of the Fmr1−/y mice phenotype to individuals with FXS. By including electrophysiological and functional readouts, the results of this study suggest the utility of both ERG and CS (ERG-CS) as complementary translational biomarkers for characterizing sensory abnormalities found in FXS, with potential applications to the clinical development of novel therapeutics that target sensory function abnormalities to treat core symptomatology in FXS. Trial registration ID-RCB number 2019-A01015-52 registered on the 17 May 2019.

Patterns of Prevalence of Multiple Sensory Impairments among Community-Dwelling Older Adults

Background Much is known about individual sensory deficits among older adults, but there is a dearth of information about the prevalence of multiple concurrent sensory deficits in this population. Methods We evaluated the prevalence of individual and multiple sensory impairments at the most recent clinic visit among participants aged 24 years and older in the Baltimore Longitudinal Study of Aging (BLSA) (hearing, vision, olfaction, proprioception, and vestibular function) and Atherosclerosis Risk in Communities Study (ARIC) (hearing, vision, olfaction). We compared observed prevalence of multiple sensory impairments with expected prevalence based on compounded probabilities of multiple impairments using Fisher Exact Tests. Also, we evaluated the comparability of different measures used between these two studies. Results In both studies, the prevalence of each individual sensory impairment was common (>10%), and higher with older age, and the most common pattern of co-occurring sensory impairments was hearing and visual impairments (17.4% [BLSA]; 50.2% [ARIC]). In BLSA, the pattern that differed the most between observed and expected prevalence was combined hearing, vision, and olfactory impairments (observed 5.2% vs. 1.4% expected, p=0.01). In ARIC, this difference was much smaller (observed 8.1% vs. 7.2% expected, p=0.49). Conclusions Although concurrent hearing and vision impairments were the most common co-occurring deficits, combined hearing, vision and olfactory impairments are most likely to co-occur above chance, especially at older ages.

Developmental exposure to non-dioxin-like polychlorinated biphenyls promotes sensory deficits and disrupts dopaminergic and GABAergic signaling in zebrafish

The most abundant polychlorinated biphenyl (PCB) congeners found in the environment and in humans are neurotoxic. This is of particular concern for early life stages because the exposure of the more vulnerable developing nervous system to neurotoxic chemicals can result in neurobehavioral disorders. In this study, we uncover currently unknown links between PCB target mechanisms and neurobehavioral deficits using zebrafish as a vertebrate model. We investigated the effects of the abundant non-dioxin-like (NDL) congener PCB153 on neuronal morphology and synaptic transmission linked to the proper execution of a sensorimotor response. Zebrafish that were exposed during development to concentrations similar to those found in human cord blood and PCB contaminated sites showed a delay in startle response. Morphological and biochemical data demonstrate that even though PCB153-induced swelling of afferent sensory neurons, the disruption of dopaminergic and GABAergic signaling appears to contribute to PCB-induced motor deficits. A similar delay was observed for other NDL congeners but not for the potent dioxin-like congener PCB126. The effects on important and broadly conserved signaling mechanisms in vertebrates suggest that NDL PCBs may contribute to neurodevelopmental abnormalities in humans and increased selection pressures in vertebrate wildlife.