Severe Functional Deficits Research Articles

Microglia LILRB4 upregulation reduces brain damage after acute ischemic stroke by limiting CD8+ T cell recruitment

BackgroundLeukocyte immunoglobulin-like receptor B4 (LILRB4) plays a significant role in regulating immune responses. LILRB4 in microglia might influence the infiltration of peripheral T cells. However, whether and how LILRB4 expression aggravates brain damage after acute ischemic stroke remains unclear. This study investigates the role of LILRB4 in modulating the immune response and its potential protective effects against ischemic brain injury in mice.Methods and resultsMicroglia-specific LILRB4 conditional knockout (LILRB4-KO) and overexpression transgenic (LILRB4-TG) mice were constructed by a Cre-loxP system. Then, they were used to investigate the role of LILRB4 after ischemic stroke using a transient middle cerebral artery occlusion (tMCAO) mouse model. Spatial transcriptomics analysis revealed increased LILRB4 expression in the ischemic hemisphere. Single-cell RNA sequencing (scRNA-seq) identified microglia-cluster3, an ischemia-associated microglia subcluster with elevated LILRB4 expression in the ischemic brain. Flow cytometry and immunofluorescence staining showed increased CD8+ T cell infiltration into the brain in LILRB4-KO-tMCAO mice. Behavioral tests, cortical perfusion maps, and infarct size measurements indicated that LILRB4-KO-tMCAO mice had more severe functional deficits and larger infarct sizes compared to Control-tMCAO and LILRB4-TG-tMCAO mice. T cell migration assays demonstrated that LILRB4-KD microglia promoted CD8+ T cell recruitment and activation in vitro, which was mitigated by CCL2 inhibition and recombinant arginase-1 addition. The scRNA-seq and spatial transcriptomics identified CCL2 was predominantly secreted from activated microglia/macrophage and increased CCL2 expression in LILRB4-KD microglia, suggesting a chemokine-mediated mechanism of LILRB4.ConclusionLILRB4 in microglia plays a crucial role in modulating the post-stroke immune response by regulating CD8+ T cell infiltration and activation. Knockout of LILRB4 exacerbates ischemic brain injury by promoting CD8+ T cell recruitment. Overexpression of LILRB4, conversely, offers neuroprotection. These findings highlight the therapeutic potential of targeting LILRB4 and its downstream pathways to mitigate immune-mediated damage in ischemic stroke.

User expectations and experiences of an assistive robotic arm in amyotrophic lateral sclerosis: a multicenter observational study

ObjectiveRobotic arms are innovative assistive devices for ALS patients with progressive motor deficits of arms and hands. The objective was to explore the patients´ expectations towards a robotic arm system and to assess the actual experiences after the provision of the device.MethodsA prospective observational study was conducted at 9 ALS centers in Germany. ALS-related functional deficits were assessed using the ALS-Functional Rating Scale-revised (ALSFRS-R). Motor deficit of the upper limbs was determined using a subscore of three arm-related items of the ALSFRS-R (items 4–6; range 0–12 points). User expectations before provision (expectation group, n = 85) and user experiences after provision (experience group, n = 14) with the device (JACO Assistive Robotic Device, Kinova, Boisbriand, QC, Canada) were assessed.ResultsIn the total cohort, mean ALSFRS-R subscore for arm function was 1.7 (SD: 2.0, 0–9) demonstrating a severe functional deficit of the upper limbs. In the expectation group (n = 85), the following use cases of the robotic arm have been prioritized: handling objects (89%), close-body movements (88%), pressing buttons (87%), serving drinks (86%), and opening cabinets and doors (85%). In the experience group (n = 14), handling objects (79%), serving drinks (79%), near-body movements (71%), pushing buttons (71%), serving food (64%), and opening doors (64%) were the most frequent used cases. Most patients used the device daily (71.4%, n = 10), and 28.6% (n = 4) several times a week. All patients of the experience group found the device helpful, felt safe while using the device, and were satisfied with its reliability. NPS of the assistive robotic arm revealed 64% "promoters" (strong recommendation), 29% "indifferents" (uncertain recommendation) and 7% "detractors" (no recommendation). Total NPS was + 57 demonstrating strong patient satisfaction.ConclusionsInitiation of procurement with a robotic assistive arm was confined to patients with severe functional deficit of the upper limbs. User experience underlined the wide spectrum of use cases of assistive robotic arms in ALS. The positive user experience together with high satisfaction underscore that robotic arm systems serve as a valuable treatment option in ALS patients with severe motor deficits of the arms.

Functional outcome after interdisciplinary, acute rehabilitation in COVID-19 patients: a retrospective study.

Survivors of severe COVID-19 often exhibit a variety of sequelae including loss of mobility and ADL (activities of daily living) capacity. Acute rehabilitation (AR) is an interdisciplinary rehabilitation intervention applied early while still in a hospital setting. The goal of AR is to improve functional limitations and to increase functional independence at discharge. It is established in the treatment of patients with other severe diseases such as sepsis, polytrauma, or stroke. Data concerning AR in COVID-19 are sparse. To evaluate the changes in physical function during AR in patients after severe COVID-19. This monocentric, retrospective observational study examined the functional outcomes of a sample of COVID-19-patients who received interdisciplinary AR at a university hospital. Inclusion criteria were a positive SARS-CoV-2 test in 05/2020-01/2022 and transfer to AR after intensive care treatment. 87 patients were elegible for evaluation, 3 of whom were excluded because of death during AR. Data were extracted from the hospital information system. In a pre-post analysis, mobility (Charité Mobility Index), ADL (Barthel Index), and oxygen demand were assessed. In addition, discharge location after AR, factors associated with AR unit length of stay, and functional improvements were analyzed. Data of 84 patients were analyzed. Mobility increased significantly from a median of 4 [1.25-6] CHARMI points at admission to a median of 9 [8.25-9] at discharge (p < 0.001). ADL increased significantly from a median of 52.5 [35.0-68.75] Barthel Index points at admission to a median of 92.5 [85-95] at discharge (p < 0.001). Oxygen demand decreased from 80.7 to 30.5% of patients. The majority (55.9%) of patients were discharged home, while 36.9% received direct follow-up rehabilitation. Older age correlated significantly with lower scores on the discharge assessment for mobility (Spearman's ϱ = -0.285, p = 0.009) and ADL (Spearman's ϱ = -0.297, p = 0.006). Acute rehabilitation is a viable option for COVID-19 patients with severe functional deficits after ICU treatment to achieve functional progress in mobility and ADL, reduce oxygen requirements and enable follow-up rehabilitation. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION FOR PROSPECTIVELY REGISTERED TRIALS: Trial registration number: DRKS00025239. Date of registration: 08 Sep 2021.

Osgood-Schlatter Disease: Ossicle Resection and Patellar Tendon Repair in a Symptomatic Adult

Chronic Osgood-Schlatter disease can cause significant knee pain and can result in severe functional deficits. For large, painful Osgood-Schlatter disease ossicles refractory to conservative management, surgical ossicle excision can provide resolution of symptoms. After diagnostic arthroscopy and intra-articular debridement, our preferred excision technique uses an open incision for direct visualization and removal of intratendinous ossicles, followed by distal patellar tendon repair and subsequent fixation with FiberTape sutures and knotless anchors to the tibial tubercle.

Interdisciplinary plastic and reconstructive surgery of head and neck squamous cell carcinomas.

Squamous cell carcinomas are the most common malignancies in the oral cavity, pharynx, and larynx. Even in the age of the most modern drug treatment methods, radical resection of these tumors is and currently remains the therapeutic gold standard. The loss of anatomical structures associated with surgery inevitably increases the functional deficits caused by the tumor itself. In this context, the extent of functional deficits is largely determined by the extent of resection. Complete organ resections, such as glossectomy, complete palate resection, laryngectomy, or transverse pharyngo-laryngectomy, lead to severe functional deficits, such as swallowing disturbances with life-threatening aspiration and articulation disorders up to the inability to speak. With the help of plastic reconstructive surgery, the lost tissue can be replaced and the specific functions of the upper aerodigestive tract can be preserved or restored.In recent decades, reconstructive surgical procedures have developed enormously in the treatment of malignant tumors of the head and neck. In order to make optimal use of them, a comprehensive, interdisciplinary therapy concept is a prerequisite for positive oncological and functional outcome. In addition to general medical and social parameters, surgical parameters play a crucial role in the choice of the reconstruction method. The extent to which the surgical measures must be interdisciplinary depends on the localization of the defects in the head and neck region and on the type of replacement tissue required. Here, the expertise of plastic surgery, oral and maxillofacial surgery, and abdominal surgery comes into play in particular. The use of different tissues, the combination of different grafts and flaps, or the preforming of donor regions allow reconstructions far beyond the level of simply restoring surface integrity. The functional results and thus the quality of life of patients after surgical therapy of extensive tumors of the mentioned localizations depend decisively on the type of reconstruction. Therefore, in the following review, special emphasis 1 be placed on the choice of reconstruction method and reconstruction technique for tissue loss after resections of HNSCC.

Major adverse foot events and functional mobility deficits associated with diabetic neuropathy and nephropathy.

The purpose is to determine the risk ratios (RR) for both major adverse foot events (MAFEs) and the presence of moderate and severe functional mobility deficits in participants with diabetic peripheral neuropathy across the stages of chronic kidney disease (CKD). We studied 284 participants with diabetes mellitus, peripheral neuropathy, and CKD. MAFEs including foot fracture, ulcerations, Charcot neuropathic arthropathy (CN), osteomyelitis, and minor foot amputations were collected from foot x-ray reports in the medical records of 152 participants; functional mobility deficits were assessed in 132 participants using the modified physical performance test (mPPT). Moderate mobility deficit was categorized as mPPT scores 22-29 and severe mobility deficit as < 22. Unadjusted and adjusted (age, body weight, race, HbA1c) RR were calculated across each stage of CKD, with stage 1 CKD used as the reference group. The RR for neuropathic foot fracture, CN, and diabetic foot ulceration remained consistent across CKD stages. The RR of minor amputation is greater in CKD stages 4 and 5. The RR of moderate or severe mobility deficit is greater in CKD stages 3 and 5 and in CKD stages 3, 4, and 5, respectively. An inverse association was observed between MAFE prevalence and mPPT scores across CKD stages. Major adverse foot events and functional mobility deficits are prevalent in individuals with DPN and diabetic kidney disease. The risks for minor foot amputation and functional mobility deficits increase as early as stage 3 CKD and increase further in stages 4 and 5.

Evaluation of routine laboratory markers as short-term outcome indicators in patients with acute ischemic stroke

Abstract Introduction: Stroke is a disease with high mortality and morbidity. Currently, there are no specific laboratory markers that can replace or improve clinical and radiological diagnosis and prognosis. We evaluated the role of C-reactive protein (CRP), fibrinogen and D-dimer in predicting short-term outcomes in acute ischemic stroke. Methods: We included 118 acute ischemic stroke patients, admitted within 24 h of onset, mean age 72.73±10.08 years. The severity of the stroke was assessed by the National Institutes of Health Stroke Scale (NIHSS), and for poor outcome (PO) we accepted a severe functional deficit at the end of the hospital stay with NIHSS ≥15, and for good outcome (GO) – NIHSS ≤ 14. In all patients, we monitored the dynamics of CRP, fibrinogen and D-dimer and evaluated their predictive value regarding to the PO and GO of the stroke. Results: D-dimer had the strongest poor predictive value at admission (p&lt;0.001). Six hours after admission, CRP, D-dimer or both were higher in PO patients (p=0.046, p=0.022 and p=0.006, respectively). At the 24.h, only CRP could be used to predict PO (p&lt;0.001). Elevated CRP, D-dimer or both have been determined as strong indicators of PO with 72 hours of admission (p&lt;0.001, p=0.032 and p=0.001, respectively). Fibrinogen levels were higher 72 hours after admission without a significant relationship with the NIHSS. Conclusion: Changes in routine biomarkers CRP and D-dimer, but not fibrinogen, can predict short-term stroke prognosis and may be associated with the risk of early neurological deterioration or death during hospital stay.

Electrical stimulation of the cuneiform nucleus enhances the effects of rehabilitative training on locomotor recovery after incomplete spinal cord injury.

Most human spinal cord injuries are anatomically incomplete, leaving some fibers still connecting the brain with the sublesional spinal cord. Spared descending fibers of the brainstem motor control system can be activated by deep brain stimulation (DBS) of the cuneiform nucleus (CnF), a subnucleus of the mesencephalic locomotor region (MLR). The MLR is an evolutionarily highly conserved structure which initiates and controls locomotion in all vertebrates. Acute electrical stimulation experiments in female adult rats with incomplete spinal cord injury conducted in our lab showed that CnF-DBS was able to re-establish a high degree of locomotion five weeks after injury, even in animals with initially very severe functional deficits and white matter lesions up to 80-95%. Here, we analyzed whether CnF-DBS can be used to support medium-intensity locomotor training and long-term recovery in rats with large but incomplete spinal cord injuries. Rats underwent rehabilitative training sessions three times per week in an enriched environment, either with or without CnF-DBS supported hindlimb stepping. After 4 weeks, animals that trained under CnF-DBS showed a higher level of locomotor performance than rats that trained comparable distances under non-stimulated conditions. The MLR does not project to the spinal cord directly; one of its main output targets is the gigantocellular reticular nucleus in the medulla oblongata. Long-term electrical stimulation of spared reticulospinal fibers after incomplete spinal cord injury via the CnF could enhance reticulospinal anatomical rearrangement and in this way lead to persistent improvement of motor function. By analyzing the spared, BDA-labeled giganto-spinal fibers we found that their gray matter arborization density after discontinuation of CnF-DBS enhanced training was lower in the lumbar L2 and L5 spinal cord in stimulated as compared to unstimulated animals, suggesting improved pruning with stimulation-enhanced training. An on-going clinical study in chronic paraplegic patients investigates the effects of CnF-DBS on locomotor capacity.

Abstract 241: Outcomes of Statins Post‐Endovascular Thrombectomy in Ischemic Stroke

Introduction Acute large vessel occlusions (LVOs) represent one‐third of acute ischemic strokes (AIS). LVOs are associated with high mortality and severe functional deficits. Several factors have been reported to play a role in improving outcomes after Endovascular Thrombectomy (EVT). Previous animal studies indicated that statins may have a protective effect on vessel wall injury caused by mechanical thrombectomy. We conducted a retrospective study to analyze whether pretreatment with statins influence the clinical and safety outcomes of EVT in AIS. Methods We conducted a retrospective observational study using the TriNetX database, a global health research network that provides access to electronic medical records retrieved from multiple international healthcare organizations but predominantly from the United States. We collected data about patients' diagnoses (using ICD‐10‐CM codes), medical procedures, medications, and demographics. Investigators were blinded to patients’ personal information or identification of participating healthcare organizations. Our study included adult patients with AIS who received EVT treatment (either extirpation or dilation procedure) between January 4, 2018, and December 31, 2022. The study patients were categorized into two groups based on whether or not they were on statins (Rosuvastatin, Simvastatin, Pravastatin, Atorvastatin, Lovastatin or Pitavastatin) during 3 months prior to hospitalization for AIS. Thirty‐day timepoint assessment was chosen to analyze the primary outcome (all‐cause mortality) and secondary outcomes [intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), decompressive hemicraniectomy procedure (DHC), and aspiration pneumonia]. The chi‐square χ2 test was used to analyze baseline characteristics for categorical variables and the independent‐sample t‐test was used for continuous variables. Matching propensity scores (with a tolerance level of 0.01 and the difference between propensity scores ≤ 0.1) were used to control differences in the comparison cohorts. Results We identified 11,972 patients who received EVT for LVO ischemic stroke. A total of 5,839 patients were on statins during 3 months prior to EVT and 6,133 were not on statins. After 1:1 propensity matching, 1,602 patients were included in each group. Kaplan‐Meier survival analysis showed the 30‐day mortality rates were significantly less for patients who were on statins compared to those who were not and with higher survival probability [87.2% vs. 77.5%, hazard ratio 0.54; confidence interval (CI): 0.45,0.64]. In comparison to EVT patients who were not on statins, those who were on statins had significantly lower rates of ICH [9.9 vs 14.1%; odds ratio (OR) 0.67; 95% CI (0.53,0.84)], lower rates of SAH [4.1 vs. 6.3%; OR 0.64; 95% CI (0.46,0.89)] and lower rates of aspiration pneumonia [5.6 vs 8.3%; OR 0.66; 95% CI (0.50,0.88)]. There was no significant difference in rates of DHC in the statins group in comparison to patients who were not on statins [1.8 vs 2.4%; OR 0.74; 95% CI (0.45,1.22)]. Conclusion Pretreatment with statins was associated with significantly better survival, less bleeding risks, and lower complication rates in LVO ischemic strokes post‐EVT. Future studies may help examine the differential effects of statin type and dose intensity on LVO strokes treated with EVT.

Avoiding the posterior interosseous nerve during 2-incision distal biceps tendon repair: an anatomic study.

The posterior interosseous nerve (PIN) is the most commonly injured motor nerve during distal biceps tendon repair resulting in severe functional deficits. Anatomic studies of distal biceps tendon repairs have evaluated the proximity of the PIN to the anterior radial shaft in supination, but limited studies have evaluated the location of the PIN in relation to the radial tuberosity (RT), and none have examined its relation to the subcutaneous border of the ulna (SBU) with varying forearm rotation. This study evaluates the location of the PIN in relation to the RT and SBU to help guide surgeons in safe placement of the dorsal incision and the safest zones of dissection. The PIN was dissected from arcade of Frohse to 2 cm distal to the RT in 18 cadaver specimens. Four lines were drawn perpendicular to the radial shaft at the proximal, middle, and distal aspect of and 1 cm distal to the RT in the lateral view. Measurements were recorded with a digital caliper along these lines to quantify the distance between the SBU and RT to the PIN with the forearm in neutral, supination, and pronation with the elbow at 90° flexion. Measurements were also made along the length of the radius at the volar, middle, and dorsal surfaces at the distal aspect of the RT to assess its proximity to the PIN. Mean distances to the PIN were greater in pronation than supination and neutral. The PIN crossed the volar surface of the distal aspect of the RT -6.9±4.3 mm (-13, -3.0) in supination, -0.4±5.8 mm (-9.9, 2.5) in neutral, and 8.5±9.9 mm (-2.7, 13) in pronation. One centimeter distal to the RT, mean distance to the PIN was 0.54±4.3 mm (-4.5, 8.8) in supination, 8.5±3.1 mm (3.2, 14) in neutral, and 10±2.7 mm (4.9, 16) in pronation. In pronation, mean distances from the SBU to the PIN at points A, B, C, and D were 41.3±4.2, 38.1±4.4, 34.9±4.2, and 30.8±3.9 mm, respectively. PIN location is quite variable, and to avoid iatrogenic injury during 2-incision distal biceps tendon repair, we recommend placement of the dorsal incision no more than 25 mm anterior to the SBU and carrying out deep dissection proximally first to identify the RT before continuing the dissection distally to expose the tendon footprint. The PIN was at risk of injury along the volar surface at the distal aspect of the RT in 50% with neutral rotation and 17% with full pronation.

Triple Semi-Circular Canal Occlusion and Cochlear Implantation: A Treatment Option for Single-Sided Menière's Disease with Functional Deafness-A Case Series.

The surgical options for patients with single-sided Menière's disease and functional deafness are challenging. Our case series reports the outcomes of surgical treatments of patients with single-sided Menière's disease and functional deafness. These patients have undergone a one-staged occlusion of all semi-circular canals and cochlear implantation. Five patients (four female and one male; 62 ± 8.2 years with a range from 50 to 72 years) with single-sided Menière's disease and functional deafness were included in this study. In all cases, the patients suffered from frequent rotational vertigo episodes for many years. Other treatment options (e.g., medication) had not yet been successful. Preoperatively, the Dizziness Handicap Inventory (DHI) of all patients indicated severe emotional, physical, and functional deficits. Patients showed a functional (near-total) deafness of the affected ear in all cases. All patients were supplied with cochlear implants in combination with a triple occlusion of all semi-circular canals in a one-stage procedure. After a short period of increased dizziness following surgery and after the activation of the cochlear implant and CI rehabilitation (auditory-verbal therapy), vertigo control and an adequate audiological outcome were achieved. The DHI showed a constant decrease after surgery. The combination of a triple semi-circular canal occlusion and cochlear implantation can be an efficient treatment for patients with single-sided Menière's disease.

Benign peripheral nerve sheath tumors: an interdisciplinary diagnostic and therapeutic challenge

A benign peripheral nerve sheath tumor (bPNST) is a rare lesion associated with peripheral nerval structures. Symptoms may be heterogeneous, complicating diagnosis finding. Additionally, management concepts of bPNST may vary. In some cases, initial misdiagnosis leads to mistreatment resulting in severe functional deficits and chronic pain syndromes. Therefore, we analyzed patients treated for bPNST in our specialized institution with a primary focus on prior misdiagnosis and possible mistreatment. Patients with bPNSTs (schwannomas, neurofibromas, hybrid nerve sheath tumors, and perineuriomas) treated at the Neurosurgical Department between January 1, 2015, and July 31, 2021, were included. Assessment of demographics, tumor entity, tumor location, symptoms, the interval between the onset of symptoms and surgery, involved medical specialties, and outpatients’ treatment, with particular focus on initial misdiagnosis and inappropriate medical treatment, was performed. Eighty-five patients were included in the final analysis with schwannoma being the most prevalent histopathological diagnosis (schwannoma (75.3%, n=64), neurofibroma (12.9%, n=11), hybrid nerve sheath tumor (5.9%, n=5), and perineurioma (5.9%, n=5)). An incorrect primary diagnosis was detected in 44.7% (n=38), leading to suboptimal or insufficient treatment in these cases. Of those, 28.9% (n=11/38) were treated suboptimal, while 18.5% (n=7/38) underwent unnecessary invasive diagnostics. Inappropriate surgery based on prior misdiagnosis, which led to severe neurological deficits in all these cases, was reported in 26.3% (n=10/38). For the first time, our data shows the quantity and impact of incorrect initial diagnosis in bPNST causing a delay in causative treatment or resulting in unnecessary or potentially harmful treatment.

Multiple motor disorders in cerebral palsy.

To characterize motor disorders in children and young people with cerebral palsy (CP). This was a cross-sectional study of 582 children and young people with CP (mean age 9 years 7 months; range 11 months-19 years 9 months; standard deviation 4 years 11 months; 340 males) attending a rehabilitation clinic at a specialized children's hospital (May 2018-March 2020). Data on motor disorders, topography, functional classifications, and non-motor features, such as epilepsy, intellectual disability, and sensory impairments, were collected using the Australian Cerebral Palsy Register CP Description Form. Fifty-five per cent (n = 321) of children and young people with CP presented with multiple motor disorders, often affecting the same limb(s). The most common motor disorders were spasticity and dystonia (50%), spasticity only (36%), and dystonia only (6%), but 18 different combinations were identified, including choreoathetosis, ataxia, and generalized hypotonia with increased reflexes. Children with spasticity only had less severe functional deficits (p < 0.001) and lower rates of associatedintellectual disability (p < 0.01) and epilepsy (p < 0.001) than those with both spasticity and dystonia. Multiple motor disorders in children and young people with CP are common and associated with more severe functional impairment. Accurate assessment of motor disorders is essential to guide prognosis and ensure personalized evidence-based interventions. More than half of children and young people with cerebral palsy presented with multiple motor disorders. Dystonia was identified in 60% of study participants. Dystonia was associated with more severe functional impairments and rates of non-motor features.

Depression status and functional outcome of patients with ischemic stroke and the impact on caregivers living in Chengdu: a cross-sectional study.

To investigate the associations between risk factors and depression symptoms in ischemic stroke (IS) survivors and the effect of IS survivors' depression status and functional outcomes on caregiver burden in Chengdu, China. In this cross-sectional study, we recruited a convenience sample of patients with IS and paired caregivers living in Chengdu from February 2022 to May 2022. Depression symptoms were assessed using the 17-item Chinese Hamilton Depression Rating Scale, the social support of patients was assessed using the perceived social support scale (PSSS), caregiver burden was assessed using the Zarit burden interview (ZBI). Multivariable logistic regression analysis was used to analyze the data between risk factors and depression symptoms, and multiple linear regression models were constructed to examine the depression symptoms and functional outcomes of stroke survivors, and caregiver burden. In total, 966 IS survivors and paired caregivers were included in this study. Among IS survivors, 35.51% (343/966) experienced depression. Age [adjusted odds ratio (aOR), 1.02; 95% confidence interval (CI), 1.00-1.04; p = 0.036], the National Institutes of Health Stroke Scale (NIHSS) score (aOR, 1.57; 95% CI, 1.47-1.68; p < 0.001), and PSSS score (aOR, 0.86; 95% CI, 0.84-0.89; p < 0.001) were associated with an increased risk of depression. The NIHSS score (b = 2.57, p < 0.001), patients' depression status (b = 2.54, p < 0.001), duration of care (b = 0.359, p = 0.006), and social support of caregivers (b = -0.894, p = 0.038) were significantly associated with the ZBI score. The PSSS score was a major risk factor for the development of depression in IS survivors, and patients' depression status and severe functional deficits had a negative impact on the ZBI score of the main caregivers. Social support can reduce the ZBI score.

Knockout of microglial Hv1 proton channel reduces neurotoxic A1 astrocytes and neuronal damage via the ROS/STAT3 pathway after spinal cord injury.

Spinal cord injury (SCI) causes severe functional deficits and neuronal damage, accompanied by intense glial activation. The voltage-gated proton channel Hv1, selectively expressed on microglia, is associated with SCI progression. However, the effect of Hv1 on the phenotypes and functions of reactive astrocytes after SCI remains unclear. Here, we combined Hv1 knockout (Hv1-/- ) mice and T10 spinal cord contusion to investigate the effects of microglial Hv1 on SCI pathophysiology and the phenotypes and functions of reactive astrocytes. After SCI, astrocytes proliferated and activated in the peri-injury area and exhibited an A1-dominant phenotype. Hv1 knockout reduced neurotoxic A1 astrocytes and shifted the dominant phenotype of reactive astrocytes from A1 to A2, enhancing synaptogenesis promotion, phagocytosis, and neurotrophy of astrocytes. Moreover, synaptic and axonal remodeling as well as motor recovery after SCI benefited from the improved astrocytic functions of Hv1 knockout. Furthermore, exogenous and endogenous reactive oxygen species (ROS) in astrocytes after SCI were reduced by Hv1 knockout. Our in vitro results showed that inhibition of ROS reduced the neurotoxic A1 phenotype in primary astrocytes via the STAT3 pathway. Similar to the effect of Hv1 knockout, the application of the ROS scavenger N-acetylcysteine reduced SCI-induced neurotoxic A1 astrocytes in vivo. Based on the in vivo and vitro results, we elucidated that microglial Hv1 knockout promotes synaptic and axonal remodeling in SCI mice by decreasing neurotoxic A1 astrocytes and increasing neuroprotective A2 astrocytes via the ROS/STAT3 pathway. Therefore, the Hv1 proton channel is a promising target for the treatment of SCI.

Exploring community reintegration among Nigerian stroke survivors.

Community reintegration is one of the ultimate goals of stroke rehabilitation. The increasing burden of stroke morbidity by other non-communicable diseases in Nigeria indicated the need for our study. The authors explored the factors contributing to successful community reintegration among Nigerian stroke survivors. We conducted an explorative qualitative study design to achieve this aim using in-depth semi-structured interviews with 12-purposively sampled stroke survivors. Three overarching themes emerged: restriction of participation experienced by stroke survivors, activity limitation as pointers to the quality-of-life experience of stroke survivors and enablers or barriers to community reintegration for stroke survivors. Among the core, sub-themes included incapability of returning to work, difficulty performing domestic activities, social isolation or separation, recreation and leisure time. Enablers of community reintegration included creating a positive mindset, encouragement and social support, while barriers included mobility and speech or language challenges. Stroke survivors have challenges in returning to work and experience varying levels of activity limitation, which affects their quality of life with identifiable enablers or barriers to community reintegration. Stroke survivors with severe functional deficits should be monitored closely and given further rehabilitative assistance to aid functional recovery, thereby facilitating community reintegration.

Transcriptome profiling of a synergistic volumetric muscle loss repair strategy

Volumetric muscle loss overwhelms skeletal muscle’s ordinarily capable regenerative machinery, resulting in severe functional deficits that have defied clinical repair strategies. In this manuscript we pair the early in vivo functional response induced by differing volumetric muscle loss tissue engineering repair strategies that are broadly representative of those explored by the field (scaffold alone, cells alone, or scaffold + cells) to the transcriptomic response induced by each intervention. We demonstrate that an implant strategy comprising allogeneic decellularized skeletal muscle scaffolds seeded with autologous minced muscle cellular paste (scaffold + cells) mediates a pattern of increased expression for several genes known to play roles in axon guidance and peripheral neuroregeneration, as well as several other key genes related to inflammation, phagocytosis, and extracellular matrix regulation. The upregulation of several key genes in the presence of both implant components suggests a unique synergy between scaffolding and cells in the early period following intervention that is not seen when either scaffolds or cells are used in isolation; a finding that invites further exploration of the interactions that could have a positive impact on the treatment of volumetric muscle loss.

Surgery as an Effective Therapy for Ulnar Nerve Neuropathic Pain Caused by Gunshot Wounds: A Retrospective Case Series

Peripheral nerve injuries remain a major medical problem worldwide and are associated with multiple causes, including gunshot wounds (GSWs), which are the second most common cause of brachial plexus injuries in peacetime and the main, or only, cause reported in wartime studies. The ulnar nerve (UN) is one of the most affected nerves. Peripheral nerve trauma may cause intense neuropathic pain, which is very difficult to control. Particularly UN gunshot injuries may impact individual daily life, as injuries to this nerve result in both sensory and motor deficits within the hand. We evaluated the improvement of neuropathic pain after surgical treatment in a consecutive series of 20 patients with UN injury due to GSWs. This single-center, retrospective, consecutive case series included 20 patients with UN injuries due to GSWs, who presented with excruciating neuropathic pain and underwent surgical treatment between 2005 and2017. Of injuries, 13 occurred in the right upper limb (65%); 12 patients had a high UN injury (60%). Regarding associated injuries, 8 patients had bone injuries (40%), and 4 patients had arterial injuries (20%). A neuroma in continuity was detected in 8 cases (40%), and 4 patients (20%) had shrapnel lodged within the UN. All patients had severe neuropathic pain and functional deficit, with a mean visual analog scale score of 8.45 ± 1.4 and a mean reduction of 6.95 points 12 months after surgery; 10 patients (50%) had a British Medical Research Council score ≥M3. Surgery is an effective treatment for neuropathic pain from GSWs. Early isolated external neurolysis is associated with better pain management and functional outcomes postoperatively.

Managing Multiple Schwannomatosis of Vagus and Hypoglossal Nerves: The Unanticipated Complications.

Schwannomas are rare benign tumours of the nerve sheath. Extracranial schwannomas are usually found solitary, in the absence of other features of neurofibromatosis. The non NF1/2 multiple schwannomas are collectively described as the clinical scenario called schwannomatosis. We present a rare case of two extracranial schwannomas involving vagus and hypoglossal nerves in a 22-year-old female along with an unusual surgical complication of CSF leak presenting as post-op neck mass and a review of previously reported similar cases. A thorough literature search using the MeSH terms-'schwannomatosis' or 'Multiple Schwannoma' and 'Vagal Schwannoma' and 'Hypoglossal Schwannoma', was conducted using online databases and augmentated by hand search. A total of 13 reported cases were found and reviewed. Of the 14 cases described from review of literature and our case, 50% had involvement of vagus nerve as one of the components. 12.5% had hypoglossal and cervical sympathetic plexus involvement each. All patients underwent surgical excision. Half of the patients suffered intraoperative nerve sacrifice with resultant severe functional deficits like vocal cord paralysis, Horners syndrome, hypoglossal palsy, facial palsy and eleventh nerve palsy. In our case, there was un-unusual complication of CSF leak presenting as a cervical neck mass. Multiple extracranial head and neck schwannomas are rare and their management is fraught with several complications. Decision to operate is often perplexing. However, early planned surgical excision and preservation of nerve of origin minimizes the impact on quality of life postoperatively.

Preoperative Muscle Biopsy to Assess Motor End Plate Integrity as a Predictor for Successful Nerve Transfer: A Case Report.

A 60-year-old right-hand-dominant man was referred for persistent right deltoid weakness, lateral shoulder numbness, and severe functional deficit 3 months after undergoing proximal humerus open reduction and internal fixation with plate and fibular strut allograft. Deltoid muscle biopsy demonstrated motor end plate (MEP) degeneration. After partial radial-to-axillary nerve transfer, repeat deltoid muscle biopsy revealed successful regeneration of MEPs with reinnervation of deltoid confirmed with postnerve transfer electromyography. Selective nerve transfer can successfully rescue a denervated target muscle from further degeneration by restoration of healthy MEPs.