Motor Pathways Research Articles

Retrograde peripheral nerve regeneration from sensory to motor pathways in rats: a new experimental concept in nerve repair

ABSTRACT Background The polarity of nerve grafts does not interfere with axon growth. Our goal was to investigate whether axons can regenerate in a retrograde fashion within sensory pathways and then extend into motor pathways, leading to muscle reinnervation. Methods Fifty-four rats were randomized into four groups. In Group 1, the ulnar nerve was connected end-to-end to the superficial radial nerve after neurectomy of the radial nerve in the axilla. In Group 2, the ulnar nerve was connected end-to-end to the radial nerve distal to the humerus; the radial nerve then was divided in the axilla. In Group 3, the radial nerve was divided in the axilla, but no nerve reconstruction was performed. In Group 4, the radial nerve was crushed in the axilla. Over 6 months, we behaviorally assessed the recovery of toe spread in the right operated-upon forepaw by lifting the rat by its tail and lowering it onto a flat surface. Six months after surgery, rats underwent reoperation, nerve transfers were tested electrophysiologically, and the posterior interosseous nerve (PIN) was removed for histological evaluation. Results Rats in the crush group recovered toe spread between 5 and 8 days after surgery. Rats with nerve transfers demonstrated electrophysiological and histological findings of nerve regeneration but no behavioral recovery. Conclusions Ulnar nerve axons regrew into the superficial radial nerve and then into the PIN to reinnervate the extensor digitorum communis. We were unable to demonstrate behavioral recovery because rats cannot readapt to cross-nerve transfer.

Attention and motor profiles in children with developmental coordination disorder: A neuropsychological and neuroimaging investigation.

This study aimed to (1) quantify attention and executive functioning in children with developmental coordination disorder (DCD), (2) assess whether some children with DCD are more likely to show attention difficulties, and (3) characterize brain correlates of motor and attention deficits. Fifty-three children (36 with DCD and 17 without) aged 8 to 10 years underwent T1-weighted and diffusion-weighted magnetic resonance imaging, and standardized attention and motor assessments. Parents completed questionnaires of executive functioning and symptoms of inattention and hyperactivity. We assessed regional cortical thickness and surface area, and cerebellar, callosal, and primary motor tract structure. Analyses of covariance and one-sample t-tests identified impaired attention, non-motor processing speed, and executive functioning in children with DCD, yet partial Spearman's rank correlation coefficients revealed these were unrelated to one another or the type or severity of the motor deficit. Robust regression analyses revealed that cortical morphology in the posterior cingulate was associated with both gross motor skills and inattentive symptoms in children with DCD, while gross motor skills were also associated with left corticospinal tract (CST) morphology. Children with DCD may benefit from routine attention and hyperactivity assessments. Alterations in the posterior cingulate and CST may be linked to impaired forward modelling during movements in children with DCD. Overall, alterations in these regions may explain the high rate of non-motor impairments in children with DCD. Children with developmental coordination disorder have difficulties in attention, processing speed, and executive functioning. Non-motor impairments were not interrelated or correlated with the type or severity of motor deficit. Posterior cingulate morphology was associated with gross motor skills and inattention. Gross motor skills were also associated with left corticospinal tract morphology.

Sjogren-Larsson syndrome brain volumetric reductions demonstrated with an automated software.

Sjogren-Larsson syndrome (SLS) is a neurocutaneous disease with an autosomal recessive inheritance, caused by mutations in the gene that encodes fatty aldehyde dehydrogenase (ALDH3A2), clinically characterized by ichthyosis, spastic diplegia, and cognitive impairment. Brain imaging plays an essential role in the diagnosis, demonstrating a nonspecific leukoencephalopathy. Data regarding brain atrophy and grey matter involvement is scarce and discordant. We performed a volumetric analysis of the brain of two siblings with SLS with the aim of detecting deep grey matter nuclei, cerebellar grey matter, and brainstem volume reduction in these patients. Volume data obtained from the brain magnetic resonance imaging (MRI) of the two patients using an automated segmentation software (Freesurfer) was compared with the volumes of a healthy control group. Statistically significant volume reduction was found in the cerebellum cortex, the brainstem, the thalamus, and the pallidum nuclei. Volume reduction in grey matter leads to the hypothesis that SLS is not a pure leukoencephalopathy. Grey matter structures affected in the present study suggest a dysfunction more prominent in the thalamic motor pathways.

Identifying spinal tracts transmitting distant effects of trans-spinal magnetic stimulation.

Estimating the state of tract-specific inputs to spinal motoneurons is critical to understand movement deficits induced by neurological injury and potential pathways to recovery, but remains challenging in humans. In this study we explored the capability of trans-spinal magnetic stimulation (TSMS) to modulate distal reflex circuits in young adults. TSMS was applied over thoracic spine to condition soleus H-reflexes involving sacral-level motoneurons. Three TSMS intensities below motor threshold were applied at inter-stimulus intervals (ISIs) between 2-20 ms relative to peripheral nerve stimulation (PNS). While low intensity TSMS yielded no changes in H-reflexes across ISIs, the two higher stimulus intensities yielded two phases of H-reflex inhibition: a relatively long-lasting period at 2-9 ms ISIs, and a short phase at 11-12 ms ISIs. H-reflex inhibition at 2 ms ISI was uniquely dependent on TSMS intensity. To identify the candidate neural pathways contributing to H-reflex suppression, we constructed a tract-specific conduction time estimation model. Based upon our model, H-reflex inhibition at 11-12 ms ISIs is likely a manifestation of orthodromic transmission along the lateral reticulospinal tract. In contrast, the inhibition at 2 ms ISI likely reflects orthodromic transmission along sensory fibers with activation reaching brain, before descending along motor tracts. Multiple pathways may contribute to H-reflex modulation between 4-9 ms ISIs, orthodromic transmission along sensorimotor tracts and antidromic transmission of multiple motor tracts. Our findings suggest that non-invasive TSMS can influence motoneuron excitability at distal segments and that the contribution of specific tracts to motoneuron excitability may be distinguishable based upon conduction velocities.

Bradykinesia and rigidity modulated by functional connectivity between the primary motor cortex and globus pallidus in Parkinson's disease.

The mechanisms underlying motor fluctuations in patients with Parkinson's disease (PD) are currently unclear. Regional brain stimulation reported the changing of motor symptoms, but the correlation with functional connectivity (FC) in the brain network is not fully understood. Hence, our study aimed to explore the relationship between motor symptom severity and FC using resting-state functional magnetic resonance imaging (rsfMRI) in the "on" and "off" states of PD. In 26 patients with sporadic PD, FC was assessed using rsfMRI, and clinical severity was analyzed using the motor part of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS Part III) in the on and off states. Correlations between FC values and MDS-UPDRS Part III scores were assessed using Pearson's correlation coefficient. The correlation between FC and motor symptoms differed in the on and off states. FC between the ipsilateral precentral gyrus (PreCG) and globus pallidus (GP) correlated with the total MDS-UPDRS Part III scores and those for bradykinesia/rigidity in the off state. Lateralization analysis indicated that FC between the PreCG and GP correlated with the contralateral total MDS-UPDRS Part III scores and those for bradykinesia/rigidity in the off state. Aberrant FC in cortico-striatal circuits correlated with the severity of motor symptoms in PD. Cortico-striatal hyperconnectivity, particularly in motor pathways involving PreCG and GP, is related to motor impairments in PD. These findings may facilitate our understanding of the mechanisms underlying motor symptoms in PD and aid in developing treatment strategies such as brain stimulation for motor impairment.

Mapping subcortical motor pathways in humans with startle-conditioned TMS

Subcortical motor pathways, such as the reticulospinal tract, are critical for producing and modulating voluntary movements and have been implicated in neurological conditions. Previous research has described the presence of ipsilateral motor evoked potentials (iMEPs) in the arm to transcranial magentic stimulation (TMS), and suggested they could be mediated by the uncrossed corticospinal tract or by ipsilateral cortico-reticulospinal connections. Here, we sought to elucidate the role of the reticulospinal tract in mediating iMEPs by assessing their modulation by a startling acoustic stimulus and mapping these responses across multiple upper limb effectors. In a first experiment, we delivered TMS at various intervals (1, 5, 10 and 15 ms) after a startling acoustic stimulus, known to excite the reticular formation, to elicit iMEPs in the arm. We observed robust facilitation of iMEP area when startle conditioning preceded TMS at the 10 ms interval. In a second experiment, we replicated our findings showing that both the area and number of iMEPs in the arm increases with startle conditioning. Using this technique, we observed that iMEPs are more prominent in the arm compared with the hand. In a third experiment, we also observed greater presence of iMEPs in flexor compared with extensor muscles. Together, these findings are consistent with properties of the reticulospinal tract observed in animals, suggesting that iMEPs primarily reflect reticulospinal activity. Our findings imply that we can use this approach to track modulation of cortico-reticulospinal excitability following interventions or neurological conditions where the reticulospinal tract may be involved in motor recovery.

Association of Acute Infarct Topography With Development of Cerebral Palsy and Neurologic Impairment in Neonates With Stroke.

Research investigating neonatal arterial ischemic stroke (NAIS) outcomes have shown that combined cortical and basal ganglia infarction or involvement of the corticospinal tract predict cerebral palsy (CP). The research question was whether voxel-based lesion-symptom mapping (VLSM) on acute MRI can identify brain regions associated with CP and neurodevelopmental impairments in NAIS. Newborns were recruited from prospective Australian and Swiss pediatric stroke registries. CP diagnosis was based on clinical examination. Language and cognitive-behavioral impairments were assessed using the Pediatric Stroke Outcome Measure, dichotomized to good (0-0.5) or poor (≥1), at ≥18 months of age. Infarcts were manually segmented using diffusion-weighted imaging, registered to a neonatal-specific brain template. VLSM was conducted using MATLAB SPM12 toolbox. A general linear model was used to correlate lesion masks with motor, language, and cognitive-behavioral outcomes. Voxel-wise t-statistics were calculated, correcting for multiple comparisons using family-wise error (FWE) rate. Eighty-five newborns met the inclusion criteria. Infarct lateralization was left hemisphere (62%), right (8%), and bilateral (30%). At a median age of 2.1 years (interquartile range 1.9-2.6), 33% developed CP and 42% had neurologic impairments. Fifty-four grey and white matter regions correlated with CP (t > 4.33; FWE < 0.05), including primary motor pathway regions, such as the precentral gyrus, and cerebral peduncle, and regions functionally connected to the primary motor pathway, such as the pallidum, and corpus callosum motor segment. No significant correlations were found for language or cognitive-behavioral outcomes. CP after NAIS correlates with infarct regions directly involved in motor control and in functionally connected regions. Areas associated with language or cognitive-behavioral impairment are less clear.

The effectiveness of robotic-assisted upper limb rehabilitation to improve upper limb function in patients with cervical spinal cord injuries: a systematic literature review.

Spinal Cord Injury (SCI) damages corticospinal tracts and descending motor pathways responsible for transmitting signals from the brain to the spinal cord, leading to temporary or permanent changes in sensation, motor function, strength, and body function below the site of injury. Cervical SCI (cSCI), which leads to tetraplegia, causes severe functional upper limb (UL) impairments that increase falls risk, limits independence, and leads to difficulties with activities of daily living (ADLs). Robotic therapy (RT) has been developed in recent decades as a new treatment approach for people with cervical spinal cord injuries (cSCI). The present review aimed to explore current available evidence and studies regarding the effectiveness of RT for individuals with cSCI in improving UL function, identify current research gaps and future research directions. This review was conducted by searching PubMed, CINAHL, Medline, Embase, and APA PsycInfo for relevant studies published from January 2010 to January 2022. Selected studies were analyzed with a focus on the patients' self-perception of limited UL function and level of independence in activities of daily living. In addition, the JBI Critical Appraisal checklist was used to assess study quality. A total of 7 articles involving 87 patients (74 males and 13 females) were included in the analysis, with four studies utilizing exoskeleton and three studies utilizing end-effector robotic devices, respectively. The quality of these studies varied between JBI Critical Appraisal scores of 4 to 8. Several studies lacked blinding and a control group which affected internal validity. Nevertheless, four out of seven studies demonstrated statistically significant improvements in outcome measurements on UL function and strength after RT. This review provided mixed evidence regarding the effectiveness of RT as a promising intervention approach to improve upper limb function in participants with cSCI. Although RT was shown to be safe, feasible, and reduces active therapist time, further research on the long-term effects of UL RT is still needed. Nevertheless, this review serves as a useful reference for researchers to further develop exoskeletons with practical and plausible applications toward geriatric orthopaedics.

Comparison of efficacy of intrathecal fentanyl as an adjuvant to bupivacaine and ropivacaine in lower limb orthopaedic surgeries for post-operative analgesia

Background: Sub-arachnoid block or spinal anaesthesia is a common mode of anaesthesia that is used for lower limb orthopaedic surgeries. Bupivacaine hydrochloride is a long-acting amide anaesthetic used extensively intrathecally. It has the ability to effectively block sensory and motor pathways. However, it has drawbacks, like cardiotoxicity and neurotoxicity. Ropivacaine is a long-acting amide local anaesthetic agent. It has the capacity to block sensory nerves more than motor nerves. Ropivacaine has reduced potential for neurotoxicity and cardiotoxicity. Fentanyl is a synthetic opioid. It can be added as an adjuvant to local anaesthetic agents used intrathecally. Fentanyl is characterised by its high potency, rapid serum elimination, and minimal histamine release. The blood-brain barrier can be quickly crossed by fentanyl, which takes one to two minutes to generate analgesia. Objectives: To compare post-operative analgesia in patients receiving bupivacaine with fentanyl and ropivacaine with fentanyl in lower limb orthopaedic surgeries via sub-arachnoid block; onset, duration of analgesia, duration of sensory and motor blockade; study the haemodynamic stability of patients in both groups; compare the requirement of 24 hours rescue analgesia; to compare the incidence of side effects. Methodology: This study will be a comparative interventional study which will be conducted on 60 adult patients of both sexes posted for lower limb orthopaedic surgery. They will be randomly divided into two groups with 30 patients in both groups. Group A: Patients receiving bupivacaine 3 mL with fentanyl 25 µg and Group B: Patients receiving ropivacaine 3mL with fentanyl 25 µg. The onset of and duration of block (sensory as well as motor), hemodynamic parameters, post-operative analgesia time and side effects (if any) will be recorded. Trial registration: Submitted to Clinical Trial Registry of India (CTRI) Trial REF/2023/05/067586

The adjunct use of descending neurogenic-evoked potentials when transcranial motor-evoked potentials degrade into warning criteria in pediatric spinal deformity surgery: minimizing false-positive events.

This studies objective was to evaluate the utility of descending neurogenic-evoked potentials (DNEPs) in the setting of transcranial motor-evoked potentials (TCeMEPs) degradation into warning criteria during pediatric spinal deformity surgery. An institutional spinal cord monitoring database was queried to identify all primary and revision pediatric spinal deformity cases, < / = 21years of age performed from 1/2006 to 12/2021, in which TCeMEPs were the primary motor tract assessment modality which degraded into warning criteria, with subsequent initiation of adjunct DNEPs. Fourteen surgical cases (0.42%; 3351 total cases) in fourteen patients met inclusion criteria. Mean age was 13.2years (7.5-21.3). syndromic (n = 7), kyphosis (n = 3), congenital (n = 2), and idiopathic (n = 2). Three-column osteotomies (3CO)were done in eight patients. TCeMEPs degraded into warning criteria during screw placement (n = 7), 3CO performance/closure (n = 4), or deformity correction (n = 3). DNEPs were present in all cases of warning-criteria TCeMEPs and one case had degradation of DNEPs. Intraoperative Stagnara wake-up tests were performed in only 2/14 cases, with one transient new neurologic deficit (NND). In this specific scenario, DNEPs sensitivity was 50%, specificity 100%, positive predictive value 100%, and negative predictive value 92% to detect aNND. DNEPs were useful in assessing spinal cord function in the setting of TCeMEP data degradation in complex pediatric deformity surgeries. DNEPs demonstrated a higher specificity and positive predictive value in this clinical setting than TCeMEPs when assessing long-term neurologic function after surgery. Based on this small cohort, DNEPs appear to be a useful adjunct modality to TCeMEPs, in this challenging clinical scenario.

Characterizing multiple sclerosis disease progression using a combined structural and functional connectivity metric

PurposeA combined resting state functional connectivity MRI (fcMRI) and diffusion tensor imaging (DTI) metric called structural and functional connectivity index (SFCI) was recently proposed for tracking disease status and progression in multiple sclerosis (MS). The metric combines fcMRI and transverse diffusivity (TD) along different functional pathways involved in principle symptomatic domains of MS.In a longitudinal study of patients with MS receiving the same MS therapy, initial worsening of transcallosal (TC) motor and frontoparietal (FP) cognitive networks, as measured by fcMRI and DTI over the first year was followed by stabilization in the second year of follow-up. In this study we have (i) probed relationships between individual and composite neurological measures of MS with SFCI and its individual components along TC motor and FP cognitive pathways and (ii) compared sensitivity of SFCI to treatment-induced longitudinal changes with each individual imaging measure. MethodsTwenty five patients with MS (15 female, age 42 ± 8 y) participated in this study and were scanned at 3 T whole body MRI scanner with diffusion tensor imaging (DTI) and resting-state functional connectivity MRI (fcMRI) scan protocol at baseline and 6, 12, 18 and 24 months after starting fingolimod. fcMRI and TD along TC and FP pathways were combined to form structural and functional connectivity index (SFCI) at each time point. Correlations between individual/combined neurological measures and individual imaging components/SFCI at baseline and were evaluated and compared. In addition, efficacies of individual and combined imaging metrics in tracking network integrity were compared. ResultsIndividual TD along the TC pathway was significantly inversely correlated with all individual/composite neurological scores. There were moderate correlations of TC and FP components of SFCI with most of the neurological scores, and the pathway-combined SFCI was significantly correlated with all neurological scores. Trend-level increases of both TC and FP fcMRI were observed during the second year of follow-up, both TC and FP TD increased significantly in the first year and then stabilized during the second year. A trend toward a decrease in combined imaging metrics along TC and FP were observed during the first year, followed by a trend toward an increase in these metrics during the second year, while a significant decrease in SFCI during the first year followed by a significant increase during the second year was observed. ConclusionsSFCI was more effective in tracking network integrity/disease progression than individual pathway-specific components, which supports its use as an imaging marker for MS disease status and progression.

Catatonia: A narrative review of its historical development, diagnosis, pathophysiology, and therapeutics.

Catatonia was initially a clinical presentation of certain types of schizophrenia, but basic and epidemiological evidence has demonstrated its association with multiple somatic and psychiatric conditions. We describe and discuss current clinical, etiological, pathophysiological, and therapeutic concepts regarding catatonia. We conducted a broad narrative review of articles published in MEDLINE/PubMed. The diagnosis is clinical and can be supported by additional tests, but there are psychometric instruments with different clinical focus. The most validated subtypes are inhibited and excited catatonia. It is mostly associated with somatic, neurological, affective, psychotic, and autistic spectrum disorders. Genetic factors related to oligodendrocytes have been studied in its pathophysiology. Some findings point to an imbalance in neurotransmission and density of GABA and dopamine receptors, consistent with their function in motor pathways and therapeutic response with benzodiazepines. Likewise, glutamatergic activity has been analyzed from the pathophysiological model of autoimmune encephalitis. The cortico-cortical and cortico-subcortical pathways would have a central role, including structures such as the orbitofrontal and temporal cortex, basal nuclei, and brainstem, involved in decision-making, emotion regulation, storage, planning, and motor processing. The main therapeutic lines are benzodiazepines and electroconvulsive therapy. Other interventions studied are zolpidem, antipsychotics, mood stabilizers, glutamatergic modulators, and transcranial magnetic stimulation. New neurobiological findings challenge nosological and therapeutic precepts, renewing the cycle in the conceptualization of catatonia. We highlight the affective component of the psychomotor syndrome and the role of interventions aimed at its modulation.

Elevated α5 integrin expression on myeloid cells in motor areas in amyotrophic lateral sclerosis is a therapeutic target

Amyotrophic lateral sclerosis (ALS) is a fatal disease affecting upper and lower motor neurons. Microglia directly interact with motor neurons and participate in the progression of ALS. Single-cell mass cytometry (CyTOF) analysis revealed prominent expression of α5 integrin in microglia and macrophages in a superoxide dismutase-1 G93A mouse model of ALS (SOD1G93A). In postmortem tissues from ALS patients with various clinical ALS phenotypes and disease duration, α5 integrin is prominent in motor pathways of the central and peripheral nervous system and in perivascular zones associated with the blood-brain barrier. In SOD1G93A mice, administration of a monoclonal antibody against α5 integrin increased survival compared to an isotype control and improved motor function on behavioral testing. Together, these findings in mice and in humans suggest that α5 integrin is a potential therapeutic target in ALS.

Characterization of Atypical Corticospinal Tract Microstructure and Hand Impairments in Early-Onset Hemiplegic Cerebral Palsy: Preliminary Findings.

Unilateral brain injuries occurring before at or shortly after full-term can result in hemiplegic cerebral palsy (HCP). HCP affects one side of the body and can be characterized in the hand with measures of weakness and a loss of independent hand control resulting in mirror movements. Hand impairment severity is extremely heterogeneous across individuals with HCP and the neural basis for this variability is unclear. We used diffusion MRI and tractography to investigate the relationship between structural morphology of the supraspinal corticospinal tract (CST) and the severity of two typical hand impairments experienced by individuals with HCP, grasp weakness and mirror movements. Results from nine children with HCP and eight children with typical development show that there is a significant hemispheric association between CST microstructure and hand impairment severity that may be explained by atypical development and fiber distribution of motor pathways. Further analysis in the non-lesioned (dominant) hemisphere shows significant differences for CST termination in the cortex between participants with HCP and those with typical development. These findings suggest that structural disparities at the cellular level in the seemingly unaffected hemisphere after early unilateral brain injury may be the cause of heterogeneous hand impairments seen in this population.Clinical Relevance- Quantitative measurement of the variability in hand function in individuals with HCP is necessary to represent the distinct impairments experienced by each person. Further understanding of the structural neural morphology underlying distal upper extremity motor deficits after early unilateral brain injury will help lead to the development of more specific targeted interventions that increase functional outcomes.

Preoperative tractography algorithm for safe resection of tumors located in the descending motor pathways zone.

Diffusion tensor imaging (DTI) tractography facilitates maximal safe resection and optimizes planning to avoid injury during subcortical dissection along descending motor pathways (DMPs). We provide an affordable, safe, and timely algorithm for preoperative DTI motor reconstruction for gliomas adjacent to DMPs. Preoperative DTI reconstructions were extracted from a prospectively acquired registry of glioma resections adjacent to DMPs. The surgeries were performed over a 7-year period. Demographic, clinical, and radiographic data were extracted from patients' electronic medical records. Nineteen patients (12 male) underwent preoperative tractography between January 1, 2013, and May 31, 2020. The average age was 44.5 years (range, 19-81 years). A complete radiological resection was achieved in nine patients, a subtotal resection in five, a partial resection in three, and a biopsy in two. Histopathological diagnoses included 10 patients with high-grade glioma and nine with low-grade glioma. A total of 16 perirolandic locations (10 frontal and six frontoparietal) were recorded, as well as two in the insula and one in the basal ganglia. In 9 patients (47.3%), the lesion was in the dominant hemisphere. The median preoperative and postoperative Karnofsky Performance Scores were 78 and 80, respectively. Motor function was unchanged or improved over time in 15 cases (78.9%). This protocol of DTI reconstruction for glioma removal near the DMP shows good results in low-term neurological functional outcomes.

Фенотипи геміпарезу при різному ступені порушення кортико-спінальної іннервації

The impairment of motor functions after stroke has a polymorphic structure, in which a decrease in strength, impairment of selective control of movements, and the development of a spastic syndrome are most studied. With partial lesions of the primary motor cortex and impairment of corticospinal innervation, the recovery of motor control is supported by various processes of neuroplastic reorganization. Among humans, the influence of corticospinal innervation impairments on the functional state of motor control and the development of spasticity syndrome remains poorly understood. The aim of our work was to establish the phenotypes of the functional state of motor control with different severity of corticospinal innervation impairment among patients after an ischemic stroke. We found that when the corticospinal innervation is impaired on 32.9% [31.9-28.8] the control of the distal parts of the extremities and the synergies of the proximal parts are fractionated, and when on 92.9% [96-80.5] the control of the distal parts is lost and the number of synergies of proximal parts are decreases. With complete impairment of the corticospinal innervation, remains control of primitive synergies of only the proximal parts of the extremities. The development of spastic syndrome was higher in groups with increased segmental excitability, which was not directly related to the state of corticospinal innervation impairment. Thus, the phenotype of hemiparesis with an increase of the corticospinal innervation impairment is characterized by the dominance of a decrease of the strength of the distal parts of the extremities and an impairment of proximo-distal inter-joints coordination. Restoration of strength and control of the proximal parts of the extremities, axial muscles of the trunk and regulation of the muscles tone indicate the involvement of the alternative from the corticospinal, descending cortical and subcortical motor pathways.

Fingolimod-Associated Macular Edema in the Treatment of Multiple Sclerosis.

Multiple sclerosis is a neurological disorder categorized by inflammatory processes with a high prevalence worldwide. It affects both motor and sensory pathways and is also associated with the visual pathway.Fingolimod is a commonly used drug for relapsing-remitting multiple sclerosis. It is a sphingosine 1-phosphate modulator acting on its receptors for immune cell accumulation, neuronal function, embryological development, vascular permeability, smooth muscle cell function, and endothelial barrier maintenance.This review aims to understand the processes, mechanisms, risks, and management of fingolimod-associated macular edema. Due to the anti-inflammatory properties of fingolimod, it decreases various cytokines, including interleukin (IL)-1B and IL-6, spike wave, and spike amplitude, in electrophysiological activities and decreases insoluble receptors for advanced glycation end productligand. A daily dosage of 0.5 mg of fingolimod has an increased association with macular edema. The serious adverse events of fingolimod are lymphopenia, cardiovascular events, ocular events, and carcinoma. Fingolimod decreases brain volume and increases vascular permeability, resulting in increased macular volume and damage to the blood-retinal barrier, which causes an increased risk for macular edema. Cystoid macular edema is more common in older individuals suffering from comorbidities affecting the retina, such as diabetes, or those undergoing ophthalmological surgeries. This review also highlights the importance of regular ophthalmology examinations on patients consuming fingolimod both in the initial stages and chronic use. The treatment options for macular edema include nonsteroidal anti-inflammatory drugs, acetazolamide, triamcinolone, ketorolac, corticosteroids, and intravitreal procedures.

Brain MRI detects early-stage alterations and disease progression in Friedreich ataxia.

Friedreich ataxia is a progressive neurodegenerative disorder characterized by cerebellar and spinal atrophy. However, studies to elucidate the longitudinal progression of the pathology in the brain are somewhat inconsistent and limited, especially for early-stage Friedreich ataxia. Using a multimodal neuroimaging protocol, combined with advanced analysis methods, we sought to identify macrostructural and microstructural alterations in the brain of patients with early-stage Friedreich ataxia to better understand its distribution patterns and progression. We enrolled 28 patients with Friedreich ataxia and 20 age- and gender-matched controls. Longitudinal clinical and imaging data were collected in the patients at baseline, 12, 24 and 36 months. Macrostructural differences were observed in patients with Friedreich ataxia, compared to controls, including lower volume of the cerebellar white matter (but not cerebellar grey matter), superior cerebellar peduncle, thalamus and brainstem structures, and higher volume of the fourth ventricle. Diffusion tensor imaging and fixel-based analysis metrics also showed microstructural differences in several brain regions, especially in the cerebellum and corticospinal tract. Over time, many of these macrostructural and microstructural alterations progressed, especially cerebellar grey and white matter volumes, and microstructure of the superior cerebellar peduncle, posterior limb of the internal capsule and superior corona radiata. In addition, linear regressions showed significant associations between many of those imaging metrics and clinical scales. This study provides evidence of early-stage macrostructural and microstructural alterations and of progression over time in the brain in Friedreich ataxia. Moreover, it allows to non-invasively map such brain alterations over a longer period (3 years) than any previous study, and identifies several brain regions with significant involvement in the disease progression besides the cerebellum. We show that fixel-based analysis of diffusion MRI data is particularly sensitive to longitudinal change in the cerebellar peduncles, as well as motor and sensory white matter tracts. In combination with other morphometric measures, they may therefore provide sensitive imaging biomarkers of disease progression for clinical trials.

Gene expression underlying variation in the survival skills of red drum larvae (Sciaenops ocellatus).

Mortality rates of marine fish larvae are incredibly high and can determine year-class strength. The major causes of larval mortality are predation and starvation, and the performance of larvae in survival skills that can mitigate this mortality (predator evasion, foraging) varies among individuals and cohorts, but the causes of the variation are not known. Transcriptomics can link gene expression variation to phenotypic variation at the whole-system level to investigate the molecular basis of behavioural variation. We used tag-based RNA-sequencing to examine the molecular basis of variation in predator evasion and routine swimming (trait related to foraging efficiency) in the larval red drum, Sciaenops ocellatus. We looked for functional gene networks in which interindividual variation would explain variation in larval behavioural performance. We identified co-expressed gene groups ("modules") associated with predator evasion traits and found enrichment of motor, neural and energy metabolism pathways. These functional associations and pattern of correlations between modules and traits suggest that energy availability and allocation were responsible for the magnitude of startle responses, while differential neural and motor activation were associated with differences in response latency.

BQ788 reveals glial ETB receptor modulation of neuronal cholinergic and nitrergic pathways to inhibit intestinal motility: Linked to postoperative ileus.

ET-1 signalling modulates intestinal motility and inflammation, but the role of ET-1/ETB receptor signalling is poorly understood. Enteric glia modulate normal motility and inflammation. We investigated whether glial ETB signalling regulates neural-motor pathways of intestinal motility and inflammation. We studied ETB signalling using: ETB drugs (ET-1, SaTX, BQ788), activity-dependent stimulation of neurons (high K+ -depolarization, EFS), gliotoxins, Tg (Ednrb-EGFP)EP59Gsat/Mmucd mice, cell-specific mRNA in Sox10CreERT2 ;Rpl22-HAflx or ChATCre ;Rpl22-HAflx mice, Sox10CreERT2 ::GCaMP5g-tdT, Wnt1Cre2 ::GCaMP5g-tdT mice, muscle tension recordings, fluid-induced peristalsis, ET-1 expression, qPCR, western blots, 3-D LSM-immunofluorescence co-labelling studies in LMMP-CM and a postoperative ileus (POI) model of intestinal inflammation. In the muscularis externa ETB receptor is expressed exclusively in glia. ET-1 is expressed in RiboTag (ChAT)-neurons, isolated ganglia and intra-ganglionic varicose-nerve fibres co-labelled with peripherin or SP. ET-1 release provides activity-dependent glial ETB receptor modulation of Ca2+ waves in neural evoked glial responses. BQ788 reveals amplification of glial and neuronal Ca2+ responses and excitatory cholinergic contractions, sensitive to L-NAME. Gliotoxins disrupt SaTX-induced glial-Ca2+ waves and prevent BQ788 amplification of contractions. The ETB receptor is linked to inhibition of contractions and peristalsis. Inflammation causes glial ETB up-regulation, SaTX-hypersensitivity and glial amplification of ETB signalling. In vivo BQ788 (i.p., 1mg·kg-1 ) attenuates intestinal inflammation in POI. Enteric glial ET-1/ETB signalling provides dual modulation of neural-motor circuits to inhibit motility. It inhibits excitatory cholinergic and stimulates inhibitory nitrergic motor pathways. Amplification of glial ETB receptors is linked to muscularis externa inflammation and possibly pathogenic mechanisms of POI.