Corticospinal Research Articles

A bibliometric analysis of the top 100 most cited articles on corticospinal tract regeneration from 2004 to 2024

A bibliometric analysis of the top 100 most cited articles on corticospinal tract regeneration from 2004 to 2024

Novel Meningoencephalomyelitis Associated With Vimentin IgG Autoantibodies

ImportanceAutoantibodies targeting astrocytes, such as those against glial fibrillary acidic protein (GFAP) or aquaporin protein 4, are crucial diagnostic markers for autoimmune astrocytopathy among central nervous system (CNS) autoimmune disorders. However, diagnosis remains challenging for patients lacking specific autoantibodies.ObjectiveTo characterize a syndrome of unknown meningoencephalomyelitis associated with an astrocytic autoantibody.Design, Setting, and ParticipantsThis retrospective case series study included samples collected from April 2021 to May 2024 at a tertiary referral hospital among patients with uncharacterized CNS autoimmune disorders and similar clinical and radiological features. Single-cell RNA sequencing (scRNA-seq) was performed on cerebrospinal fluid (CSF) cells of 2 index patients to identify the putative target antigen of the clonally expanded B cells. A comprehensive screening for additional patients was conducted using blinded cell-based and tissue-based assay. Candidate patients were followed up for a median (range) duration of 23 (5-31) months.ExposuresscRNA-seq, autoantibody characterization, and testing.Main Outcomes and MeasuresDetection of the autoantibody and characterization of the associated autoimmune meningoencephalomyelitis.ResultsFourteen candidate patients (10 [71%] female; median [IQR] age, 33 [23-41] years) were identified. Initially, CSF from 2 female patients with unknown encephalomyelitis showed astrocytic reactivity on rat tissue but was negative for GFAP IgG. A total of 17 of 37 clonally expanded B cell clonotypes (46%) in their CSF expressed IgG autoantibodies targeting the astrocytic intermediate filament protein vimentin. Subsequent screening identified 12 additional patients. These 14 patients shared a unique clinical profile characterized by relapsing courses and symptoms prominently involving the cerebellum, brainstem, and corticospinal tract (CST). All patients also exhibited elevated CSF protein and cells, intrathecal immunoglobulin synthesis, and magnetic resonance imaging (MRI) showing bilateral lesions on CST. Notably, 8 of 12 patients (67%) who received first-line immunotherapy at their first episode responded well. At the last follow-up, 11 patients (79%) experienced significant disability (modified Rankin Scale ≥3).Conclusions and RelevanceIn this case series, autoantibodies targeting the astrocytic intermediate filament protein vimentin were identified in patients with previously undifferentiated meningoencephalomyelitis and common radiographic features.

Premovement neuronal activity in the primary motor cortex is associated with the initiation of ipsilateral hand movements in monkeys.

The primary motor cortex (M1) is believed to be a cortical center for the execution of limb movements. Although M1 neurons mainly project to the spinal cord on the contralateral side, some M1 neurons project to the ipsilateral side via the uncrossed corticospinal pathway. Moreover, some M1 neurons are activated during ipsilateral forelimb movements. However, the extent to which M1 neurons are involved in ipsilateral movement execution has not been determined. Therefore, we investigated the involvement of M1 neurons in the initiation of ipsilateral and contralateral hand movements by examining trial-by-trial correlations between premovement neuronal spikes and hand movement reaction times in monkeys. Overall, the activity of M1 neurons was more strongly correlated with the reaction times for contralateral hand movements than those for ipsilateral hand movements. However, the activity of some M1 neurons was correlated with reaction times for ipsilateral hand movements, and these correlations were as strong as those between the activity of other M1 neurons and reaction times for contralateral hand movements. This finding suggests that one subset of M1 neurons sends motor commands for ipsilateral hand movements to the same extent as another subset of M1 neurons sends motor commands for contralateral hand movements.

Insights into the dependence of post-stroke motor recovery on the initial corticospinal tract connectivity from a computational model

There is a consensus that motor recovery post-stroke primarily depends on the degree of the initial connectivity of the ipsilesional corticospinal tract (CST). Indeed, if the residual CST connectivity is sufficient to convey motor commands, the neuromotor system continues to use the CST predominantly, and motor function recovers up to 80%. In contrast, if the residual CST connectivity is insufficient, hand/arm dexterity barely recovers, even as the phases of stroke progress. Instead, the functional upregulation of the reticulospinal tract (RST) often occurs. In this study, we construct a computational model that reproduces the dependence of post-stroke motor recovery on the initial CST connectivity. The model emulates biologically plausible evolutions of primary motor descending tracts, based on activity-dependent or use-dependent plasticity and the preferential use of more strongly connected neural circuits. The model replicates several elements of the empirical evidence presented by the Fugl-Meyer Assessment (FMA) subscores, which evaluate the capabilities for out-of-synergy and in-synergy movements. These capabilities presumably change differently depending on the degree of the initial CST connectivity post-stroke, providing insights into the interactive dynamics of the primary descending motor tracts. We discuss findings derived from the proposed model in relation to the well-known proportional recovery rule. This modeling study aims to present a way to differentiate individuals who can achieve 70 to 80% recovery in the chronic phase from those who cannot by examining the interactive evolution of out-of-synergy and in-synergy movement capabilities during the subacute phase, as assessed by the FMA.

Motor involvement in frontotemporal lobar degeneration with TAR DNA-binding protein of 43 kDa type C.

The degeneration of pyramidal tracts has been reported in frontotemporal lobar degeneration with TDP-43 (TAR DNA-binding protein 43) pathology (FTLD-TDP) type C. Herein, we examined the detailed pathology of the primary motor area and pyramidal tracts in the central nervous system in four autopsy cases of FTLD-TDP type C, all of which were diagnosed by neuropathological, biochemical, and genomic analyses. Three patients showed right dominant atrophy of the frontal and temporal lobes, while the other patient showed left dominant atrophy. All four patients showed motor symptoms, and two patients had episodes of repeated aspiration. In the primary motor area, phosphorylated TDP-43 (p-TDP-43) or annexin A11-immunoreactive long dystrophic neurites were observed in all cases, and neuronophagia of the Betz cells was frequently observed in two of four cases. In the lower motor system, p-TDP-43 or annexin A11-positive dystrophic neurites were detected in the anterior horn of the spinal cord. Immuno-electron microscopy of the insoluble fraction extracted from all cases showed p-TDP-43 or annexin A11-labelled filaments. In FTLD-TDP type C, neurodegeneration with TDP and annexin A11 pathology was observed mainly in the upper motor neurons of both patients with right- and left predominant temporal atrophy and a short disease duration. Furthermore, a combination of TDP-43 and annexin A11 pathology was visible in the lower motor neurons, albeit less frequently. In summary, we reported the TDP-43 and annexin A11-associated involvement of anterior horn cells of the spinal cord for the first time. The degeneration of the motor system could contribute to dysphagia and aspiration pneumonia at the late stage of FTLD-TDP type C. Little or no TDP pathology was found in the corticospinal tract, unlike in FTLD-TDP type B, suggesting the occurrence of secondary degeneration in FTLD-TDP type C.

Teaching NeuroImage: Wallerian Degeneration of the Corticospinal Tract After Cerebral Hemorrhage.

Teaching NeuroImage: Wallerian Degeneration of the Corticospinal Tract After Cerebral Hemorrhage.

Remodeling and Characterization Analysis of Corticospinal Tract in Patients with Intracerebral Hemorrhage in the Basal Ganglia.

To investigate corticospinal tract (CST) injury and remodeling in patients with basal ganglia intracerebral hemorrhage (ICH) and explore the characterization capabilities of the corresponding parameters. In this prospective study, baseline, scale, and diffusion-weighted imaging (DWI) data were collected from patient cohorts. Participants were stratified into favorable (0-3 points) and unfavorable (4-6 points) prognosis groups, based on Modified Rankin Scale (mRS) after 3-6months. The analysis of DWI data was conducted employing FSL and DSI Studio software to compare CST injury between the prognosis groups and CST remodeling features. A partial correlation model was deployed to elucidate the characterization capability of CST-related parameters. Additionally, logistic regression analysis was applied to identify factors significantly influencing prognosis. A total of 65 patients were enrolled with a mean age of 53.52years and a median hematoma volume of 23.60ml. The 44 patients were classified within the favorable prognosis group, demonstrating a statistically significant difference in their lower mean age (P = 0.002). Additionally, 10 patients underwent DWI review with a mean age of 50.30years and a median hematoma volume of 18.56ml. The investigation uncovered evidence of CST damage versus remodeling at the group level, respectively, with statistical significance (FDR-corrected P < 0.05, 10,000 permutations). The fractional anisotropy (FA) ratio in the internal capsule region exhibited moderate correlation with motor function (r = 0.507, P < 0.001) and the 3- to 6-month mRS scores (r = - 0.318, P < 0.013). Furthermore, binary logistic regression analysis identified the FA rate in the internal capsule as a significant influencing factor of prognosis (odds ratio = 1.027, 95% confidence interval = 1.003-1.052, P = 0.025). Basal ganglia ICH can coincide with injury to the CST, which could undergo repair over time. Additionally, the FA ratio of the internal capsule is a potential biomarker to characterize residual motor function and provide prognostic information.

Evaluation of objective methods for analyzing ipsilateral motor evoked potentials in stroke survivors with chronic upper extremity motor impairment.

Objective:Ipsilateral motor evoked potentials (iMEPs) are believed to represent cortically evoked excitability of uncrossed brainstem-mediated pathways. In the event of extensive injury to (crossed) corticospinal pathways, which can occur following a stroke, uncrossed ipsilateral pathways may serve as an alternate resource to support the recovery of the paretic limb. However, iMEPs, even in neurally intact people, can be small, infrequent, and noisy, so discerning them in stroke survivors is very challenging. This study aimed to investigate the inter-rater reliability of iMEP features (presence/absence, amplitude, area, onset, and offset) to evaluate the reliability of existing methods for objectively analyzing iMEPs in stroke survivors with chronic upper extremity motor impairment.&#xD;Approach:Two investigators subjectively measured iMEP features from thirty-two stroke participants with chronic upper extremity motor impairment. Six objective methods based on standard deviation (SD) and mean consecutive differences (MCD) were used to measure the iMEP features from the same 32 participants. IMEP analysis used both trial-by-trial (individual signal) and average-signal analysis approaches. Inter-rater reliability of iMEP features and agreement between the subjective and objective methods were analyzed (percent agreement-PA and intraclass correlation coefficient-ICC).&#xD;Main results:Inter-rater reliability was excellent for iMEP detection (PA> 85%), amplitude, and area (ICC> 0.9). Of the six objective methods we tested, the 1SD method was most appropriate for identifying and analyzing iMEP amplitude and area (ICC> 0.9) in both trial-by-trial and average signal analysis approaches. None of the objective methods were reliable for analyzing iMEP onset and offset. Results also support using the average-signal analysis approach over the trial-by-trial analysis approach, as it offers excellent reliability for iMEP analysis in stroke survivors with chronic upper extremity motor impairment.&#xD;Significance:Findings from our study have relevance for understanding the role of ipsilateral pathways that typically survive unilateral severe white matter injury in people with stroke.&#xD.

Distinction in the function and microstructure of white matter between major depressive disorder and generalized anxiety disorder.

Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are two of the leading causes of impairment to human mental health. These two psychiatric disorders overlap in many symptoms and neurobiological features thus difficult to distinguish in some cases. We enrolled 102 participants, comprising 40 patients with MDD, 32 patients with GAD and 30 matched healthy controls (HCs), to undergo multimodal magnetic resonance imaging (MRI) scans. We identified 18 major white matter (WM) tracts with automated fiber quantification (AFQ) method, to evaluated microstructure with fractional anisotropy (FA) and function with amplitude of low-frequency fluctuation (ALFF). An analysis of variance (ANOVA) was employed to identify differences among groups. We further explored the correlations of FA and ALFF features with clinical symptoms. We identified the white matter microstructure and function of 89 participants. ANOVA and post-hoc analysis revealed that GAD group exhibited significantly higher FA of right anterior thalamic radiation (ATR) than in MDD and HC groups. Additionally, MDD group exhibited significantly decreased ALFF in forceps major (FMA), forceps minor (FMI), bilateral corticospinal tracts (CST) and left inferior fronto-occipital fasciculus (IFOF) compared to both GAD and HC group. ALFF of right CST was significantly negatively correlated to HAMA and a moderate effect size and marginal significance was found between FA of the right ATR and HAMA in GAD group. This study used cross-sectional data and sample size was small. Tracking microstructure and function of WM with AFQ method has the potential to distinguish different psychiatric diseases.

Engaging dystonia networks with subthalamic stimulation

Deep brain stimulation is an efficacious treatment for dystonia. While the internal pallidum serves as the primary target, recently, stimulation of the subthalamic nucleus (STN) has been investigated. However, optimal targeting within this structure and its surroundings have not been studied in depth. Indeed, historical targets that have been used for surgical treatment of dystonia are directly adjacent to the STN. Further, multiple types of dystonia exist, and outcomes are variable, suggesting that not all types would profit maximally from the same target. Therefore, a thorough investigation of neural substrates underlying stimulation effects on dystonia signs and symptoms is warranted. Here, we analyze a multicenter cohort of isolated dystonia patients with subthalamic implantations (N = 58) and relate their stimulation sites to improvements of appendicular and cervical symptoms as well as blepharospasm. Stimulation of the ventral oral posterior nucleus of thalamus and surrounding regions were associated with improvements in cervical dystonia, while stimulation of the dorsolateral STN was associated with improvements in limb dystonia and blepharospasm. This dissociation was matched by structural connectivity analysis, where the cerebellothalamic, corticospinal, and pallidosubthalamic tracts were associated with improvements of cervical dystonia, while hyperdirect and subthalamopallidal pathways with alleviation of limb dystonia and blepharospasm. On the level of functional networks, improvements of limb dystonia were associated with connectivity to the corresponding somatotopic regions in the primary motor cortex, while alleviation of cervical dystonia to the cingulo-opercular network. These findings shed light on the pathophysiology of dystonia and may guide DBS targeting and programming in the future.

Synaptic signatures and disease vulnerabilities of layer 5 pyramidal neurons

Cortical layer 5 (L5) intratelencephalic (IT) and pyramidal tract (PT) neurons are embedded in distinct information processing pathways. Their morphology, connectivity, electrophysiological properties, and role in behavior have been extensively analyzed. However, the molecular composition of their synapses remains largely uncharacterized. Here, we dissect the protein composition of the excitatory postsynaptic compartment of mouse L5 neurons in intact somatosensory circuits, using an optimized proximity biotinylation workflow with high spatial accuracy. We find distinct synaptic signatures of L5 IT and PT neurons that are defined by proteins regulating synaptic organization and transmission, including cell-surface proteins (CSPs), neurotransmitter receptors and ion channels. In addition, we find a differential vulnerability to disease, with a marked enrichment of autism risk genes in the synaptic signature of L5 IT neurons compared to PT neurons. These results align with human studies and suggest that the excitatory postsynaptic compartment of L5 IT neurons is susceptible in autism. Our approach is versatile and can be broadly applied to other neuron types to create a protein-based, synaptic atlas of cortical circuits.

Evaluation of gray-matter and white-matter microstructural abnormalities in children with growth hormone deficiency: a comprehensive assessment with synthetic magnetic resonance imaging.

Pediatric growth hormone deficiency (GHD) is a disease resulting from the impaired growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis, but the effects of GHD on children's behavior and brain microstructural structure alterations have not yet been fully clarified. We aimed to investigate the quantitative profiles of gray matter and white matter in pediatric GHD using synthetic magnetic resonance imaging (MRI). The data of 50 children with GHD and 50 typically developing (TD) children were prospectively collected. Group differences in brain volumetric parameters, individual-level T1 and T2 relaxometry values, and myelin volume fraction (MVF) were assessed. Subsequently, magnetic resonance-based indices with significant differences between groups were correlated with clinical variables via partial correlation. Compared with TD children, children with GHD showed significantly decreased whole-brain gray-matter volume [P false discovery rate (PFDR) <0.001] and increased non-gray-matter/white-matter/cerebrospinal fluid (NoN) volume (PFDR<0.001). For gray-matter microstructural profiles, altered T1 and T2 relaxometry values in children with GHD were mainly distributed in the default mode (PFDR<0.001) and central executive networks (PFDR<0.001). For white-matter microstructural profiles, widespread increased regional MVF was mainly distributed in the corpus callosum, corticospinal tract, internal capsule, external capsule, and cingulum (all PFDR values <0.001). Meanwhile, the T2 relaxation values in the left cuneus (r=0.400; P=0.005) and MVF in the right corticospinal tract (r=0.313; P=0.032) had a positive relationship with IGF-1. Altered T1 and T2 relaxometry values and MVF in gray and white matter indicate the relevance of the default mode, central executive, somatosensory, visual, and cerebellar networks underlying pediatric GHD, which may imply the involvement of the GH-IGF-1 axis and myelin in the pathophysiological mechanism of GHD. Moreover, the brain microstructure alteration in cortico-striatal-limbic loop might be influenced by the GH-IGF-1 axis and play an important role in the behavioral impairments in children with GHD.

Motor Neuron Diseases and Central Nervous System Tractopathies: Clinical-Radiologic Correlation and Diagnostic Approach.

White matter tracts within the central nervous system are organized into ascending and descending pathways that transmit sensory input and motor output, respectively. Tractopathy, or damage to these tracts, can impair sensory or motor functions. Motor neuron diseases are pathologic processes affecting the upper or lower motor neurons. Amyotrophic lateral sclerosis (ALS) is the most common form of acquired motor neuron disease. Traditionally, ALS has affected upper and lower motor neurons of the extremities, torso, and head and neck. There are several ALS variants, some of which affect only the upper motor neurons (eg, primary lateral sclerosis), lower motor neurons (eg, progressive muscular atrophy), or motor neurons of the head and neck (eg, progressive bulbar palsy). Characteristic imaging features of ALS include abnormal T2 hyperintensity within the brain along the corticospinal tract, as well as cortical susceptibility signal intensity along the precentral gyrus, termed the "motor band" sign. Spinal muscular atrophy is a less common primary motor neuron disease and appears on images as atrophy of the anterior horn of the spinal cord, as well as proximal muscle atrophy. In addition to pure motor neuron diseases, there are numerous toxic and metabolic conditions, genetic disorders, infectious diseases, and immune-mediated disorders that can secondarily affect the corticospinal tracts (corticospinal tractopathies), producing symptoms of upper motor neuron injury. These tractopathies are visible at MRI as T2-hyperintense lesions along varying segments of the corticospinal tract. A comprehensive diagnostic approach that integrates clinical symptoms with radiologic and laboratory findings is crucial to distinguish among these varied conditions. ©RSNA, 2024 Supplemental material is available for this article.

Neural structural alterations correlates of quadriceps muscle strength deficits in patients after anterior cruciate ligament reconstruction.

Persistent maladaptive changes of corticospinal tract (CST) and quadriceps strength deficits exist in patients with anterior cruciate ligament reconstruction (ACLR). This study aimed to investigate the relationships between the structural alterations of CST and quadriceps muscle strength deficits in patients with ACLR. Twenty-nine participants who had undergone unilateral ACLR (29 males; age=32.61±6.72 years) were enrolled in a cross-sectional investigation. We chose CST as a region of interest and performed diffusion tensor imaging (DTI) that measured the microstructure of white matter tracts. Maximal voluntary isometric quadriceps muscle strength was assessed using a hand-held dynamometer. Simple and partial correlation analyses were performed between the DTI outcomes and quadriceps muscle strength deficits in patients with ACLR before and after controlling for age, sex, BMI, Tegner activity score, and graft type. Sub-group analyses were also performed to investigate the relationships between the DTI outcomes of CST structure and quadriceps muscle strength deficits according to the graft type before and after controlling for age, sex, BMI, and Tegner activity score. Lower limb symmetry index (LSI) of quadriceps muscle strength was associated with a higher ratio of radial diffusivity (RD, r=-0.379, p=0.042) in corticospinal tracts of the injured hemisphere to those of the non-injured hemisphere in ACLR patients after controlling for age, BMI, Tegner activity score and graft type. In subgroup analyses of ACLR patients with hamstring autografts, we found that higher injured quadriceps muscle strength was associated with higher axial diffusivity (AD, r=0.616, p=0.033) of CST structure and lower LSI of quadriceps muscle strength was associated with higher ratio of mean diffusivity (MD, r=-0.682, p=0.014) and RD (r=-0.759, p=0.004) in corticospinal tracts of the injured hemisphere to those of the non-injured hemisphere in ACLR patients after controlling for age, BMI, Tegner activity score. Decreased integrity (higher ratio of RD) of CST microstructure in ACLR patients was significantly associated with lower quadriceps limb symmetry index, which hinted that quadriceps muscle strength deficits of injured side may be a demyelinating process of CST microstructure in ACLR.

MR study on white matter injury in patients with acute diquat poisoning

To explore the microstructural damage of white matter in acute diquat (DQ) poisoning patients using diffusion kurtosis imaging (DKI) and Tract-based Spatial Statistics (TBSS). This study included 19 DQ poisoning patients and 19 age-matched controls. MRI was performed using a 3.0 T Philips Achieva scanner with sequences including 3D T1WI, T2WI, DWI, 3D T2WI-FLAIR, and DKI (3 b-values, 15 directions). DICOM to NIFTI image form conversion was done using MRIcron's Dcm2niigui, followed by motion and eddy current correction with FSL to create a brain mask. Scalar indicators (MK, AK, RK, FAK) were calculated with DKE software. TBSS was used for spatial normalization, skeletonization, and projection of DKI indices for group analysis with TFCE for multiple comparison correction (P < 0.025). After the screening and enrollment process, 19 DQ-poisoned patients and 19 healthy volunteers were analyzed. No significant age or sex differences were found between groups. For Mean Kurtosis (MK), the right corticospinal tract showed a significant difference with a mean difference of 0.21 (95 % CI: 0.15-0.27) and P = 0.000503. Axial Kurtosis (AK) in the left superior longitudinal fasciculus had a mean difference of 0.18 (95 % CI: 0.12-0.24) and P = 0.0024. Fractional Anisotropy of Kurtosis (FAK) in the right corticospinal tract showed a mean difference of 0.19 (95 % CI: 0.13-0.25) and P = 0.0000318. Axial Kurtosis (AK) positively correlated with blood drug levels (r = 0.52, P < 0.05). Seven patients developed subcortical leukodystrophy, mainly in the frontal parietal lobe, with possible insular lobe involvement. DQ poisoning primarily damages the right corticospinal tract, right cingulate gyrus, and left superior longitudinal fasciculus, potentially causing movement and visual impairments. The injury involves demyelination and axonal degeneration, with asymmetrical damage between hemispheres. The left superior longitudinal fasciculus injury is dose-dependent, and unlike prior studies, dopaminergic nuclei were unaffected. The frontal parietal lobe is predominantly affected, with some insular lobe involvement in DQ poisoning patients.

In vivo mapping of sodium homeostasis disturbances in individual ALS patients: A brain 23Na MRI study.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by significant heterogeneity among patients. 23Na MRI maps abnormal sodium homeostasis that reflects metabolic alterations and energetic failure contributing to the neurodegenerative process. In this study, we investigated disease severity at the individual level in ALS patients using brain 23Na MRI. 1H and 23Na brain MRI were collected prospectively from 28 ALS patients. Individual map of abnormal total sodium concentration (TSC) was computed using voxel-based statistical mapping for each patient compared to a local database of 62 healthy controls. Clinical data included the revised ALS functional rating scale (ALSFRS-R), ALSFRS-R slope, ALSFRS-R at 6-month and survival time. Individual maps quantifying voxels with TSC increase evidenced a high heterogeneity between patients consistent with clinical presentation. The main areas involved were the corticospinal tracts. Half of patients showed abnormal TSC increase within more than 1% of whole brain voxels. Patients with TSC increase had worse clinical severity: higher ALSFRS-R slope (p = 0.02), lower ALSFRS-R at 6-month (p = 0.04), and shorter survival (p = 0.04). ALS patients with limited TSC increase had slower progression of disability or predominant lower motor neuron phenotype or shorter disease duration. This study mapping sodium homeostasis disturbances at the individual level in ALS patients through 23Na MRI evidenced heterogeneity of TSC increase among patients associated with clinical presentation and disease severity. These findings suggest that TSC increase detected at the individual level by 23Na MRI may be a useful marker of the clinical heterogeneity of ALS patients, a factor that is likely to greatly influence the results of therapeutic trials.

Therapeutic Intervention for Trunk Control Impairments in Central Nervous System Disorders: A Comprehensive Review of Methods and Efficacy.

Trunk control involves multiple brain regions related to motor control systems. Therefore, patients with central nervous system (CNS) disorders frequently exhibit impaired trunk control, decreasing their activities of daily living (ADL). Although some therapeutic interventions for trunk impairments have been effective, their general effects on CNS disorders remain unclear. This review aimed to clarify this issue in patients with stroke, cerebellar ataxia, and Parkinson's disease (PD), representing trunk control impairment by lesions in the cortical and corticospinal systems, cerebellum, and basal ganglia, respectively. Using online databases, we searched for randomized controlled trials that investigated the effects of therapeutic interventions for trunk impairments in patients with stroke, cerebellar ataxia, and PD, reported in English from 2013 to 2023. Overall, 50 articles were reviewed. Core-stability exercise (CSE), which activates the trunk muscles, specifically in the lumbar and pelvic areas, through postural adjustment tasks, is effective in patients with stroke, cerebellar ataxia, and PD. Weight-shifting exercise, unstable surface training, training with transcutaneous electrical stimulation, and noninvasive brain stimulation have been effective in patients following stroke. The combination of CSE with task-oriented training based on daily activities has been effective in patients with cerebellar ataxia. Perceptual training, repetitive trans-spinal magnetic stimulation, and aquatic training effectively improved alignment and balance function in patients with PD. This review provides evidence-based strategies to improve trunk control, ADL, and quality of life for patients with trunk control impairments caused by CNS disorders.

Hyperactive delta isoform of PI3 kinase enables long-distance regeneration of adult rat corticospinal tract.

Neurons in the CNS lose regenerative potential with maturity, leading to minimal corticospinal tract (CST) axon regrowth after spinal cord injury (SCI). In young rodents, knockdown of PTEN, which antagonizes PI3K signaling by hydrolyzing PIP3, promotes axon regeneration following SCI. However, this effect diminishes in adults, potentially due to lower PI3K activation leading to reduced PIP3. This study explores whether increased PIP3 generation can promote long-distance regeneration in adults. We used a hyperactive PI3K, PI3Kδ (PIK3CD), to boost PIP3 levels in mature cortical neurons and assessed CST regeneration after SCI. Adult rats received AAV1-PIK3CD and AAV1-eGFP, or AAV1-eGFP alone, in the sensorimotor cortex concurrent with a C4 dorsal SCI. Transduced neurons showed increased pS6 levels, indicating elevated PI3K/Akt/mTOR signaling. CST regeneration, confirmed with retrograde tracing, was evaluated up to 16weeks post injury. At 12weeks, ∼100 axons were present at lesion sites, doubling to 200 by 16weeks, with regeneration indices of 0.1 and 0.2, respectively. Behavioral tests showed significant improvements in paw reaching, grip strength, and ladder-rung walking in PIK3CD-treated rats, corroborated by electrophysiological recordings of cord dorsum potentials and distal flexor muscle electromyography. Thus, PI3Kδ upregulation in adult cortical neurons enhances axonal regeneration and functional recovery post SCI.

Upper-extremity motor recovery after stroke: A systematic review and meta-analysis of usual care in trials and observational studies.

A better knowledge of upper-extremity (UE) recovery in patients with stroke receiving usual care (UC) is crucial for informing clinicians on expected recovery and serves as reference for future studies. This systematic review and meta-analysis aimed to assess rate and amount of recovery of UE with UC in the subacute phase of stroke and identify covariates of UE recovery. PRISMA-guidelines were used for search in PubMed, Cinahl and PEDro. Observational studies (OS) and UC groups of randomized control trials (RCT) of adults with subacute stroke and UE paresis were included, each reporting UE function at least at two time points. Placebo-, sham-controlled, dose-matched trials and trials with <10 participants were excluded. From 1220 records, 54 papers (19 OS and 35 RCTs) involving 2774 subacute stroke patients were included. Fugl-Meyer Assessment of Upper Extremity (FMA-UE) and Action Research Arm Test (ARAT) were most frequently reported UE outcomes. Across RCTs, FMA-UE and ARAT improved 10 and 8 points, respectively, on average at 4-weeks from baseline. In OS, FMA-UE, improved 12 points at 12weeks and 16 points at 24weeks from baseline. Stroke severity, UE function, and lesion load of the cortico-spinal tract at baseline were associated with UE recovery. UE function in subacute stroke showed improvements that exceeded the threshold for clinically important change across RCTs and OS. This review provides estimates of expected change in UC groups for sample size calculations and planning of future trials, thereby enhancing statistical power and comparability of findings.

Cerebrotendinous Xanthomatosis occurs at high frequency in Ashkenazi Jews.

Cerebrotendinous Xanthomatosis (CTX) is a treatable, inborn error of bile acids metabolism caused by pathogenic variants in CYP27A1. CTX is a multi-organ system disorder that progresses over decades. Clinical features include cerebellar dysfunction, pyramidal tract dysfunction, cognitive deficits and decline, peripheral neuropathy, chronic diarrhea, bilateral cataracts, and tendon xanthomas. Treatment is effective when started early, but diagnostic delays often result in individuals not being diagnosed until after the window of highest treatment efficacy. CTX is documented to occur in most global populations, however, no CTX-causing genetic variants have been reported in Ashkenazi Jews. We conducted a systematic review of every case of CTX reported in a person identified as Jewish and the specific CYP27A1 variants present. We also leveraged the Israeli Medical Genetics Database and the population genetics data resource gnomAD to identify CTX-causing alleles in Ashkenazi Jews. We found that there are three pathogenic CYP27A1 variants in the Ashkenazi Jewish population segregating at an appreciable frequency, with a gene carrier rate of 0.002 based on the gnomAD Ashkenazi Jewish data. One pathogenic variant appears only in the Ashkenazi Jewish group in gnomAD, which contains genetic data from across the globe. We compared the carrier frequency for CTX to the carrier frequencies for diseases that are commonly included in carrier screening for Ashkenazi Jews. These results show that CTX occurs in Ashkenazi Jews, and that both Sephardi and Ashkenazi Jews may benefit from newborn and carrier screening for CTX.