Palsy Research Articles

Hypoxia-inducible factor-1 as targets for neuroprotection : from ferroptosis to Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease characterized by motor paralysis, tremor,and cognitive impairment. Risk factors such as brain hypoxia caused by aging and abnormal expression of HIF-1α areconsidered to be key to the development of PD, including α-synuclein accumulation and ferroptosis. However, therelationship between HIF-1α signaling and ferroptosis in PD has not been elucidated. The stable expression of HIF-1αinhibits the pathological development of PD. Aging aggravates PD pathology by promoting α-synuclein accumulationand oxidative stress. The literature on lipid peroxidation, oxidative stress, iron metabolism and other key factors in Parkinson'sdisease in recent years was reviewed through a variety of literature search channels, such as PubMed and Elsevier. HIF-1α mediated ferroptosis through oxidative stress and GPX4-GSH system. HIF-1α mediates ferroptosisthrough Keap1-Nrf2-ARE, Grx3 and Grx4. HIF-1α mediates ferroptosis through iron metabolism. This article reviews the oxygen-dependent regulatory mechanism of HIF-1α and its role in cerebralhypoxia homeostasis. Studies in the past decade have shown that Hif-1α mediated ferroptosis is important in PD.HIF-1α has a dual role, depending on the degree of cellular hypoxia and the environment. The equilibrium complexityneeds to be explained, and the role of ferroptosis needs to be investigated. The literature shows that the stabilizationof HIF-1α with PHD inhibitors and the combination of antioxidants and iron chelators are potential therapeuticdirections. In the future, the optimal use time and dose of inhibitors should be studied to improve the efficacy.

Identifying Factors for Predicting Postoperative Segmental Motor Paralysis in Patients Undergoing Anterior Cervical Spine Surgery: A Multicenter Study.

Retrospective cohort study. To investigate the incidence of and risk factors for segmental motor paralysis after anterior cervical spine surgery. Segmental motor paralysis is a potential complication following both anterior and posterior cervical decompression procedures; however, previous studies investigating risk factors for segmental motor paralysis after anterior cervical spine surgery were limited by small sample sizes. Consequently, the exact pathogenesis and risk factors for this complication remain poorly understood, highlighting the need for larger-scale investigations focused exclusively on anterior cervical spine surgeries. We retrospectively reviewed the clinico-demographic and operative factors and postoperative outcomes of 1,428 patients undergoing anterior cervical spine surgery at three spine centers in Japan. Postoperative segmental motor paralysis was defined as deterioration of upper extremity muscle strength by ≥1 grade; recovery was defined as a return to preoperative muscle strength levels. Univariate and multivariate analyses were performed to identify risk factors. Ninety-nine patients (6.9%) developed segmental motor paralysis, mostly involving the C5 segment (81.8%), the incidence being highest in patients with ossification of the posterior longitudinal ligament (OPLL) and those undergoing anterior cervical corpectomy and fusion or hybrid fusion (discectomy + corpectomy). Older age, male sex, higher body mass index, OPLL, and cervical corpectomy were independent risk factors for paralysis, with these patients having significantly worse clinical outcomes at 1 year postoperatively. Most patients (74/99, 79.6%) regained preoperative muscle strength levels an final follow up. This study identified important clinico-demographic and operative risk factors for segmental motor paralysis after anterior cervical spine surgery. Patients undergoing corpectomy, with or without OPLL, were found to be at particularly high risk. While most patients recover well, worse outcomes with segmental motor paralysis highlight the importance of preventing this complication, particularly for OPLL patients and corpectomy procedures. III.

Brown Sequard Syndrome: A Case Report

A very unusual neurological disorder known as Brown-Séquard Syndrome (BSS) may develop when the spinal cord is severed or damaged on one side. Ipsilateral motor paralysis, loss of proprioception, and a lack of pain and temperature sensitivity on the opposite side are hallmarks of this disorder's distinctive pattern of neurological impaired functions. A 45-year-old man with a history of severe injuries who acquired Brown-Séquard Syndrome is the subject of this case report.

Impact of Health Access on Hospitalization of Children and Youth with Cerebral Palsy and Paralytic Syndromes in Brazilian Regions.

In 2021, 28.16% of Brazilians were aged 0-19 years, highlighting the critical need for medical care in diagnosing and treating cerebral palsy (CP). In developing countries, CP prevalence reaches 7/1000 live births, emphasizing the importance of healthcare access, which influences diagnosis and prognosis. This study aimed to analyze the correlation between health infrastructure across different Brazilian regions and its impact on hospitalization and mortality rates among children with CP and other paralytic syndromes. An ecological time-series design was used, analyzing secondary population-based data from DATASUS, covering January 2018 to December 2021. The data included healthcare facilities, physicians, hospitalizations, and deaths for individuals aged 0-19 years, with analysis conducted using Microsoft Excel. The results revealed significant disparities in healthcare infrastructure, particularly in the northern and northeastern regions. A notable correlation was found between healthcare inequalities and hospitalizations and mortality rates, with the northern region showing significant results (p = 0.03 for hospitalizations and p = 0.02 for mortalities). This study underscores significant regional disparities in healthcare access in Brazil, contributing to variations in hospitalization rates for children and adolescents, especially in the northern region.

Psychiatric, Neurological, and Somatic Comorbidities in Intermittent Explosive Disorder: a retrospective cohort study of electronic health records.

Intermittent Explosive Disorder (IED) is an understudied psychiatric condition that presents with repeated episodes of impulsive aggression and poorly regulated emotional control, often resulting in interpersonal and societal consequences. Better understanding of comorbidities will allow for enhanced screening, diagnosis, and treatment of patients. To investigate prevalence and associations of IED with psychiatric, neurological, and somatic disorders using real-world data. Matched cohorts of patients with or without IED diagnosis were identified using data from the TriNetX Research Network (until January 31, 2024). Cox proportional hazard models were used to estimate and compare the probabilities of acquiring other diagnoses using patients' available medical records. Analysis of electronic medical records from two patient populations. 30,357 individuals with IED and equal number of demographically matched individuals without IED from the TriNetX Research. IED diagnosis identified through the associated ICD codes. The main outcomes were ICD-10-CM diagnostic categories and root codes for disorders and health conditions in both cohorts. Main measures are total numbers and proportions of patients who had the diagnostic codes, as well as adjusted hazard ratios for IED diagnosis. Although only 0.03% of the total patient population had an IED diagnosis, we found extensive and widespread comorbidities with psychiatric, neurological and somatic conditions. A significant 95.7% of the individuals with IED had another psychiatric diagnosis. All psychiatric sub-categories and 95% of the psychiatric diagnoses were significantly associated with IED, with HRs ranging from 2 to 77. Among neurological conditions, neurodegenerative diseases and epilepsy had the highest HRs, followed by extrapyramidal and movement disorders, cerebral palsy and other paralytic syndromes, and sleep disorders. Notable associations with IED also includes conditions such as obesity, hyperlipidemia, hypertension, and GERD. Our findings illuminate the extensive comorbid relationships between IED and psychiatric, neurological, and somatic disorders. This underscores the necessity for an integrated diagnostic and treatment approach that addresses both the psychological and physical health aspects of IED. Additionally, our work highlights the need for more accurate and inclusive diagnosis of IED in patients with mental disorders.

Nuclear Localization of Human SOD1 in Motor Neurons in Mouse Model and Patient Amyotrophic Lateral Sclerosis: Possible Links to Cholinergic Phenotype, NADPH Oxidase, Oxidative Stress, and DNA Damage.

Amyotrophic lateral sclerosis (ALS) is a fatal disease that causes degeneration of motor neurons (MNs) and paralysis. ALS can be caused by mutations in the gene that encodes copper/zinc superoxide dismutase (SOD1). SOD1 is known mostly as a cytosolic antioxidant protein, but SOD1 is also in the nucleus of non-transgenic (tg) and human SOD1 (hSOD1) tg mouse MNs. SOD1's nuclear presence in different cell types and subnuclear compartmentations are unknown, as are the nuclear functions of SOD1. We examined hSOD1 nuclear localization and DNA damage in tg mice expressing mutated and wildtype variants of hSOD1 (hSOD1-G93A and hSOD1-wildtype). We also studied ALS patient-derived induced pluripotent stem (iPS) cells to determine the nuclear presence of SOD1 in undifferentiated and differentiated MNs. In hSOD1-G93A and hSOD1-wildtype tg mice, choline acetyltransferase (ChAT)-positive MNs had nuclear hSOD1, but while hSOD1-wildtype mouse MNs also had nuclear ChAT, hSOD1-G93A mouse MNs showed symptom-related loss of nuclear ChAT. The interneurons had preserved parvalbumin nuclear positivity in hSOD1-G93A mice. hSOD1-G93A was seen less commonly in spinal cord astrocytes and, notably, oligodendrocytes, but as the disease emerged, the oligodendrocytes had increased mutant hSOD1 nuclear presence. Brain and spinal cord subcellular fractionation identified mutant hSOD1 in soluble nuclear extracts of the brain and spinal cord, but mutant hSOD1 was concentrated in the chromatin nuclear extract only in the spinal cord. Nuclear extracts from mutant hSOD1 tg mouse spinal cords had altered protein nitration, footprinting peroxynitrite presence, and the intact nuclear extracts had strongly increased superoxide production as well as the active NADPH oxidase marker, p47phox. The comet assay showed that MNs from hSOD1-G93A mice progressively (6-14 weeks of age) accumulated DNA single-strand breaks. Ablation of the NCF1 gene, encoding p47phox, and pharmacological inhibition of NADPH oxidase with systemic treatment of apocynin (10 mg/kg, ip) extended the mean lifespan of hSOD1-G93A mice by about 25% and mitigated genomic DNA damage progression. In human postmortem CNS, SOD1 was found in the nucleus of neurons and glia; nuclear SOD1 was increased in degenerating neurons in ALS cases and formed inclusions. Human iPS cells had nuclear SOD1 during directed differentiation to MNs, but mutant SOD1-expressing cells failed to establish wildtype MN nuclear SOD1 levels. We conclude that SOD1 has a prominent nuclear presence in the central nervous system, perhaps adopting aberrant contexts to participate in ALS pathobiology.

Pneumatic Plantar Stimulation Device Replicating Manual Therapy Improves Lateral Stability in Standing Posture

Strokes are a widespread condition characterized by motor paralysis and sensory impairment, and they significantly hinder daily activities. Hence, rehabilitation aimed at improving motor function is crucial for post-stroke patients. Manual therapy, which involves the manual stimulation of the limbs to provide sensory input and enhance motor function, is commonly employed for rehabilitation. However, the limited duration of inpatient rehabilitation highlights the need for devices that can provide similar rehabilitation interventions at home. Here we elucidate the skills employed by physical therapists during intervention through interviews and measurements of the force applied to the plantar surface of the foot. Subsequently, we develop a device capable of replicating these intervention skills. The investigation of physical-therapist skills revealed the importance of stimulating the muscles involved in forming the longitudinal and transverse arches and the flexor muscles of the toes during manual therapy. The required force for stimulation was also noted. Using our device, which utilized pneumatic actuation to replicate therapist skills, intervention on the plantar surface of the feet of healthy adults demonstrated improved stability in their standing posture, particularly in the lateral direction. These devices can enhance the sensory-motor connection from the plantar surface, thereby improving motor abilities, such as preventing falls.

Effects of basic movements and gait in the case of homolateral imitative synkinesis

BackgroundHomolateral Imitative Synkinesis (HIS) is a rare form of associative movement between the ipsilateral upper and lower limbs. The incidence of HIS or its correlation with various movements remains uninvestigated. This study expounds on the characteristics of HIS, the frequency at which it occurs, and its relationship with movement, particularly walking. MethodsThis study included 1328 patients with acute stroke admitted to our healthcare facility between October 2019 and February 2022. We evaluated the severity of motor paralysis and sensory impairment in instances where HIS manifested, and assessed the relationship between HIS, basic activities, and gait. ResultsHIS was observed in 13/1328 patients. Motor paralysis was mild in all the cases. Each patient displayed a degree of sensory impairment, albeit of varying severity. HIS did not manifest during basic activities but was evident during walking movements in five instances. These patients displayed involuntary repetitive lifting of their upper limbs during the swing phase of their gait. Some individuals expressed discontent with involuntary upper-limb movements, citing them as contributors to a suboptimal gait. ConclusionsThis study identified HIS as a rare syndrome, manifesting at a rate of 0.9%. Focus was more common in patients with damage to the thalamus and parietal lobe. No manifestations of the HIS occurred during basic activities, suggesting a weak correlation between the HIS and such activities. Certain patients exhibit HIS during gait, report suboptimal gait, and have an increased risk of falls, potentially influencing their gait proficiency.

Classification of physiotherapy exercise of stroke patients using deep transfer learning and fuzzy logic: A novel approach

According to the world health organization (WHO), stroke stands as a significant contributor to mortality and adult disability, causing motor function impairment, paralysis, and intense back pain. In aiding stroke patients' mobility recovery, physiotherapists employ diverse therapeutic techniques. This research introduces an automated method for identifying distinct therapeutic exercises performed by stroke patients during their rehabilitation process. For detecting rehabilitation exercises, leveraging pre-trained neural networks like GoogLeNet, InceptionV3, ResNet-101, DenseNet-201, Xception, InceptionResNetV2, and DarkNet-53, all potent models trained on extensive datasets. The proposed models were trained on a dataset of 2250 diverse RGB images to classify eight rehabilitation exercises: Elbow Extension, Knee Flexion, Neck Exercise, Planter Flexion of Foot, Trunk Extension, Trunk Flexion, Wrist Extension, and Wrist Flexion. The resulting average validation accuracies are as follows: InceptionV3 (97.4%), Xception (97.3%), ResNet101 (97.3%), DarkNet53 (96.7%), GoogLeNet (95.9%), DenseNet201 (94.3%), and InceptionResNetV2 (93.4%). Fuzzy EDAS is then employed to rank the models. This ranking suggests that the inception-v3 model has high rank for most of the classes and is highly recommended for physiotherapy exercises classification.

Feasibility of a neurorehabilitation pipeline and an automated algorithm to select appropriate treatments for upper extremity motor paralysis in individuals with chronic stroke.

This study aimed to investigate the feasibility of a neurorehabilitation pipeline and develop an algorithm to automatically select the appropriate treatment for individuals with upper extremity motor paralysis after stroke in the chronic phase. In Experiment 1, eight post-stroke participants in the chronic phase who underwent treatment sustaining two to three phases were assessed before and after treatment. In Experiment 2, a decision tree analysis was performed in which the dependent variable was set as the treatment option determined by a board-certified physiatrist for 95 post-stroke participants; the independent variables were only motor function scores or both motor function scores and electromyogram variables. In Experiment 1, the clinical assessment scores were improved significantly after treatment. Experiment 2 showed that the agreements of the model with only motor function scores as the dependent variable and with motor function scores and electromyogram variables as the dependent variables were 75.8% and 82.1%, respectively. This novel treatment package is feasible for improvement of motor function in post-stroke individuals with severe motor paralysis. The study also established an automated algorithm for selecting appropriate treatments for upper extremity motor paralysis after stroke, identifying standard values of key variables, including electromyography variables.

Jean-Martin Charcot, member of thesis juries at the Paris medical school (1862–1893)

ABSTRACT Jean-Martin Charcot is considered the founding father of modern neurology. There are many general and specialized biographies about him, the result being that a new text is unexpected or would likely amount to plagiarism. However, part of the duties for Charcot’s medical professorship have not, to date, been studied at all. This article will focus on the role of Charcot as a member of doctorate juries and, in particular, as the president of these juries. I have reviewed around 12,500 theses one by one. These were defended at the Paris medical school from 1862, Charcot’s first year as an agrégé (assistant professor), to his death in 1893. Among the theses, I have selected all of those that discuss neuropsychiatry in the broadest terms (3,663). I have paid particular attention to all of those for which Charcot was part of the jury. This involves 608 theses. All of the data were entered in a database (Filemaker) to facilitate identifying those theses corresponding to one or more of the criteria. Statistical comparisons were then carried out (Excel spreadsheet). In addition to these results, brief individualized surveys were conducted on theses selected for their representativeness, either for the subject matter (multiple sclerosis, aphasia, tabes, general paralysis, etc.) or for specific criteria (foreigners, women, etc.), but all of the theses were defended before a jury that included Charcot. This makes it possible to track how the areas of study in the medical world changed over time, and particularly those of Charcot. The juries Charcot was obliged to be a part of, without any particular ties to the candidate and/or any involvement in the selection and supervision of the work, must be differentiated from the thesis juries for his students. In the latter case, the thesis subjects were most often linked to Charcot’s researches. Providing a thesis subject was motivated, in certain cases, by the desire to disseminate new data in the medical profession, not only by dint of the theses themselves but also through the reports that the medical press published regularly (e.g. the diagnosis of various types of shaking) and through the commercial publication of these data, in some cases with a preface by Charcot. In other cases, the thesis was a step in the long process of developing a theory (hysteria). Or it led to a flowering of new ideas, insufficiently proven, which Charcot would only cover in his Lessons once there was convincing confirmation (amyotrophy). This rich cornucopia gives rise to certain neglected nuggets, as well as works that have entered the classical corpus—for example, the theses of Léopold Ordenstein, Ivan Poumeau, Isaac Bruhl, Albert Gombault, and Pierre Janet.

A decision tree algorithm to identify predictors of post-stroke complex regional pain syndrome

This prospective cohort study aimed to identify the risk factors for post-stroke complex regional pain syndrome (CRPS) using a decision tree algorithm while comprehensively assessing upper limb and lower limb disuse and physical inactivity. Upper limb disuse (Fugl-Meyer assessment of upper extremity [FMA-UE], Action Research Arm Test, Motor Activity Log), lower limb disuse (Fugl-Meyer Assessment of lower extremity [FMA-LE]), balance performance (Berg balance scale), and physical inactivity time (International Physical Activity Questionnaire-Short Form [IPAQ-SF]) of 195 stroke patients who visited the Kishiwada Rehabilitation Hospital were assessed at admission. The incidence of post-stroke CRPS was 15.4% in all stroke patients 3 months after admission. The IPAQ, FMA-UE, and FMA-LE were extracted as risk factors for post-stroke CRPS. According to the decision tree algorithm, the incidence of post-stroke CRPS was 1.5% in patients with a short physical inactivity time (IPAQ-SF < 635), while it increased to 84.6% in patients with a long inactivity time (IPAQ-SF ≥ 635) and severe disuse of upper and lower limbs (FMA-UE score < 19.5; FMA-LE score < 16.5). The incidence of post-stroke CRPS may increase with lower-limb disuse and physical inactivity, in addition to upper-limb disuse. Increasing physical activity and addressing lower- and upper-limb motor paralysis may reduce post-stroke CRPS.

Landmarks in the history of neurosyphilis: the neglected observations of Vincenzo Chiarugi.

After the emergence of syphilis in Europe in 1495, it would take over 400 years to unpick the full course of the infection, including the involvement of the brain and spinal cord. This syndrome of mental and physical deterioration was called 'general paralysis of the insane' (GPI). Traditionally, the earliest clear description of GPI is attributed to Haslam in 1798. However, here I describe three clear cases and three highly suggestive cases, together with autopsy findings, published in 1794 by the Italian psychiatrist Vincenzo Chiarugi. Historically, Chiarugi's scholarship has been neglected in favour of English- and French-speaking physicians. His observations also give a rare clue regarding the prevalence of syphilis, suggesting a foothold in northern Italy in the late eighteenth century.

Mối liên quan giữa lâm sàng và hình ảnh học của nhồi máu não tái phát do tổn thương động mạch não giữa

Objectives: Evaluate the relationship between clinical and imaging of recurrent cerebral infarction dued to MCA damaged. Subjects and method: A cross-sectional, descriptive study of 77 patients with recurrent cerebral infarction dued to damaged middle cerebral artery treated at the Neurological Center, Bach Mai Hospital from July 2021 to August 2022. Results: Motor paralysis of the hemibody on the opposite side of the injury, paralysis of the central VII nerve on the opposite side of the injury and decreased sensation of the hemibody on the opposite side of the injury are symptoms seen at a high rate, accounting for 100% respectively; 90.9% and 77.9%. The proportion of patients with consciousness disorders from the beginning accounted for 49.4% of patients, 2 patients were in a deep coma when hospitalized (accounting for 2.6%). Language disorders including Broca’s language disorder, Wernicke’s language disorder and mixed language disorder accounted for 20/77 patients (26.0%). Horizontal eye and head deviation, circular muscle disorders, loss of attention on one side of the body, and hemianopia account for 32.5% respectively; 26.0%; 22.1%; 26.0%. 7.8% of patients had mental disorders and 14.3% of patients had seizures when hospitalized; The symptoms of headache, nausea, and vomiting accounted for 45.5% and 31.2%, respectively. Patients with symptoms clustered into Gerstman syndrome and Anton - Babinski syndrome account for a low rate: 9.1% and 11.7%. The most damaged arterial branch is the M1 branch with 31 patients, accounting for 40.2%; Oblique branches of the middle cerebral artery or putamen-striatum branches account for 32.5%. Only 4 patients had damage to branches M3 - M4 (accounting for 5.2%). The number of patients with damage to the M1 branch who had consciousness disorders accounted for the highest rate of 33.8%, with no patients with damage to the deep branch having consciousness disorders. Symptoms at hospital admission: consciousness disorders, speech disorders, turning eyes and head to the damaged hemisphere have a statistically significant relationship with the location of the damaged middle cerebral artery branch (p &lt; 0.05)Conclusion: Recurrent cerebral infarction due to damage to the middle cerebral artery has diverse clinical symptoms, depending on the damaged middle cerebral artery branch.

Association between the initial physical activity and functional recovery after 1 month of inpatient rehabilitation for subacute stroke: stratified analysis by nutritional status.

Objectively measured physical activity volume serves as a predictive factor for functional recovery in patients with stroke. Malnutrition, a frequent complication of stroke, may influence the relationship between physical activity and functional recovery. This study aimed to examine the association between physical activity volume and functional recovery in patients with stroke, stratified by their nutritional status. This multicenter prospective observational study included 209 patients with stroke admitted to two Japanese convalescent rehabilitation hospitals. Participants were categorized based on the geriatric nutritional risk index (GNRI) at admission [≥92, high GNRI group ( n = 133); <92, low GNRI group ( n = 76)]. Physical activity levels were measured as the duration of total physical activity (TPA), which is the sum of light-intensity physical activity and moderate-to-vigorous physical activity, using a triaxial accelerometer during the first 7 days after admission. Outcome measures are represented as the relative gain of the motor score on functional independence measure (M-FIM effectiveness) during the first month after admission. The multiple regression analysis, adjusting for age, sex, comorbidity, onset to admission intervals, motor paralysis, initial M-FIM, and cognitive FIM, showed that the duration of TPA in the first 7 days was significantly associated with the M-FIM effectiveness over the first month in both low GNRI [ B = 0.12, 95% confidential intervals (CI) = 0.01; 0.24, P = 0.049] and high GNRI group ( B = 0.11, 95% CI = 0.01; 0.21, P = 0.027). This study demonstrates a positive predictive association between early TPA level and functional recovery in stroke patients, irrespective of their nutritional status.

Minimal clinically important difference in physical activity in patients with stroke

Background Estimates of the minimal clinically important difference (MCID) for stroke-related outcomes are needed, but the MCID for physical activity is unknown. Objective To provide an anchor-based estimate of the MCID for physical activity in patients with stroke. Methods This study included 31 patients with stroke admitted to a hospital and discharged home. Physical activity, including the daily number of steps and metabolic equivalents (METs), was evaluated shortly after informed consent was obtained following admission (baseline) and discharge using an Active-style Pro HJA-750C with a triaxial accelerometer. We calculated the number of steps and time rate (%) of sedentary behavior (SB), light-intensity physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) per day. After discharge, the physical therapist rated each participant’s perceived amount of physical activity recovery on the Global Rating of Change scale (GRC). The mean change in each physical activity data point from baseline to after discharge in the group of participants who answered “a little better, meaningful” in the GRC was considered the MCID. Results Eighteen participants were included in the analysis. Participants’ physical function improved from baseline to at discharge during hospitalization, although mild motor paralysis persisted. MCID values for the step activity, SB, LPA, and MVPA were 1828 steps, -11.2%, 6.9%, 4.3% per day, respectively. Conclusion For researchers and clinicians, this study’s MCIDs provide a benchmark for interpreting changes in the effects of intervention studies, and specific guidelines for interventions in clinical practice. Further research with larger sample sizes is required to confirm these findings.

Neuropathic pain development and maintenance and its association with motor recovery after cervical spinal cord injury

Background In our published randomized controlled trial, we revealed that patients with acute ASIA Grade C incomplete cervical spinal cord injury (SCI) who underwent early surgery (within 24 h post-injury) had accelerated motor recovery at six months than those with delayed surgery (>2 weeks post-injury); however, neuropathic pain (NeP) worsened regardless of surgery timing. Here, we conducted post-hoc analyses to intensively assess NeP development and maintenance. Methods Of 44 patients (median 64.5 years; three female; early intervention, n = 26), NeP was categorized into at-level and below-level pain and evaluated at two weeks and one year after injury using the Neuropathic Pain Symptom Inventory (NPSI). We compared the two groups based on background characteristics. A mixed-design analysis of variance with sex as a covariate was conducted to analyze motor recovery and Health-related quality of life (HRQOL) in groups with severe (NPSI ≥ 10) or mild (NPSI < 10) pain. Results Upper and lower limb motor impairments were comparable between both groups regardless of pain severity. Severe at-level pain remained stable and worsened at one year than mild at-level pain; however, the upper- and lower-limb motor scores and HRQOL had comparable recovery. Background characteristics did not affect severity or time course of NeP. Patients with severe below-level pain demonstrated slower lower-limb motor recovery than those with mild below-level pain, whereas HRQOL improved regardless of pain severity. Conclusions Both at-level and below-level NeP developed and persisted relatively early in the course of traumatic SCI with incomplete motor paralysis; their severities worsened over time or remained severe since onset.

Changes in Structural Neural Networks in the Recovery Process of Motor Paralysis after Stroke.

In recent years, neurorehabilitation has been actively used to treat motor paralysis after stroke. However, the impacts of rehabilitation on neural networks in the brain remain largely unknown. Therefore, we investigated changes in structural neural networks after rehabilitation therapy in patients who received a combination of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) and intensive occupational therapy (intensive-OT) as neurorehabilitation. Fugl-Meyer assessment (FMA) for upper extremity (FMA-UE) and Action Research Arm Test (ARAT), both of which reflected upper limb motor function, were conducted before and after rehabilitation therapy. At the same time, diffusion tensor imaging (DTI) and three-dimensional T1-weighted imaging (3D T1WI) were performed. After analyzing the structural connectome based on DTI data, measures related to connectivity in neural networks were calculated using graph theory. Rehabilitation therapy prompted a significant increase in connectivity with the isthmus of the cingulate gyrus in the ipsilesional hemisphere (p < 0.05) in patients with left-sided paralysis, as well as a significant decrease in connectivity with the ipsilesional postcentral gyrus (p < 0.05). These results indicate that LF-rTMS combined with intensive-OT may facilitate motor function recovery by enhancing the functional roles of networks in motor-related areas of the ipsilesional cerebral hemisphere.

Characteristics of limb kinematics in the gait disorders of post-stroke patients

Post-stroke gait disorders involve altered lower limb kinematics. Recently, the endpoint of the lower limb has been used as a control variable to understand gait kinematics better. In a cross-sectional study of sixty-seven post-stroke patients, the limb extension angle and effective limb length during gait were used as input variables with a mixed Gaussian model-based probabilistic clustering approach to identify five distinct clusters. Each cluster had unique characteristics related to motor paralysis, spasticity, balance ability, and gait strategy. Cluster 1 exhibited high limb extension angle and length values, indicating increased spasticity. Cluster 2 had moderate extension angles and high limb lengths, indicating increased spasticity and reduced balance ability. Cluster 3 had low limb extension angles and high limb length, indicating reduced balance ability, more severe motor paralysis, and increased spasticity. Cluster 4 demonstrated high extension angles and short limb lengths, with a gait strategy that prioritized stride length in the component of gait speed. Cluster 5 had moderate extension angles and short limb lengths, with a gait strategy that prioritized cadence in the component of gait speed. These findings provide valuable insights into post-stroke gait impairment and can guide the development of personalized and effective rehabilitation strategies.

An optogenetic cell therapy to restore control of target muscles in an aggressive mouse model of amyotrophic lateral sclerosis

Breakdown of neuromuscular junctions (NMJs) is an early pathological hallmark of amyotrophic lateral sclerosis (ALS) that blocks neuromuscular transmission, leading to muscle weakness, paralysis and, ultimately, premature death. Currently, no therapies exist that can prevent progressive motor neuron degeneration, muscle denervation, or paralysis in ALS. Here, we report important advances in the development of an optogenetic, neural replacement strategy that can effectively restore innervation of severely affected skeletal muscles in the aggressive SOD1G93A mouse model of ALS, thus providing an interface to selectively control the function of targeted muscles using optical stimulation. We also identify a specific approach to confer complete survival of allogeneic replacement motor neurons. Furthermore, we demonstrate that an optical stimulation training paradigm can prevent atrophy of reinnervated muscle fibers and results in a tenfold increase in optically evoked contractile force. Together, these advances pave the way for an assistive therapy that could benefit all ALS patients.