Uncrossed Corticospinal Tract Research Articles

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.

Clinical features and genotypes of six patients from four families with horizontal gaze palsy with progressive scoliosis

BackgroundHorizontal gaze palsy with progressive scoliosis (HGPPS) is a rare disorder mainly involved in ocular movement and spinal development. It is caused by a roundabout guidance receptor 3 (ROBO3) gene mutation. This study aimed to describe the clinical features of six patients with HGPPS and investigate the corresponding ROBO3 gene mutations.MethodsPatients underwent detailed clinical and imaging examinations. Whole-exome sequencing was performed to detect nucleotide variations in the disease-causing genes of HGPPS.ResultsSix pathogenic variants were detected in the ROBO3 gene from six patients with HGPPS, including two novel compound heterozygous mutations, c.1447C > T (p.R483X) and c.2462G > C (p.R821P); c.1033G > C (p.V345L) and c.3287G > T (p.C1096F); a novel homozygous indel mutation, c.565dupC (p.R191Pfs*61); and a known missense mutation, c.416G > T (p.G139V). Patients with HGPPS had horizontal conjugated eye movement defects and scoliosis with variable degrees, as well as flattened pontine tegmentum and uncrossed corticospinal tracts on magnetic resonance imaging.ConclusionOur genetic findings will expand the spectrum of ROBO3 mutations and help inform future research on the molecular mechanism of HGPPS.

Ipsilateral motor pathways to the lower limb after stroke: Insights and opportunities.

Stroke-related damage to the crossed lateral corticospinal tract causes motor deficits in the contralateral (paretic) limb. To restore functional movement in the paretic limb, the nervous system may increase its reliance on ipsilaterally descending motor pathways, including the uncrossed lateral corticospinal tract, the reticulospinal tract, the rubrospinal tract, and the vestibulospinal tract. Our knowledge about the role of these pathways for upper limb motor recovery is incomplete, and even less is known about the role of these pathways for lower limb motor recovery. Understanding the role of ipsilateral motor pathways to paretic lower limb movement and recovery after stroke may help improve our rehabilitative efforts and provide alternate solutions to address stroke-related impairments. These advances are important because walking and mobility impairments are major contributors to long-term disability after stroke, and improving walking is a high priority for individuals with stroke. This perspective highlights evidence regarding the contributions of ipsilateral motor pathways from the contralesional hemisphere and spinal interneuronal pathways for paretic lower limb movement and recovery. This perspective also identifies opportunities for future research to expand our knowledge about ipsilateral motor pathways and provides insights into how this information may be used to guide rehabilitation.

Uncrossed corticospinal tracts in a patient with ichthyosis and hemiparesis: a case report

BackgroundAnomalies of pyramidal tract decussation are rare phenomena that can be caused by ectodermal dysplasia. Herein, we describe a patient with ichthyosis who exhibited ipsilateral hemiparesis after stroke and whose neuroimaging results showed evidence of motor control being provided by the ipsilateral motor cortex.Case presentationA 24-year-old right-handed man presented with skin abnormalities, sudden-onset left hemiparesis, and dysarthria. He exhibited a mild-to-moderate left-sided weakness (grade 4 on the Medical Research Council scale). Magnetic resonance imaging revealed an acute infarct in the left corona radiata. Diffusion tensor imaging revealed uncrossed corticospinal tracts. Next-generation sequencing identified heterozygous FLG mutations. The patient was diagnosed with cerebral infarction and ichthyosis vulgaris and was treated with aspirin (100 mg/d). His symptoms gradually dissipated.ConclusionsThis case suggests that pyramidal decussation anomalies can be associated with ichthyosis. Patients with ichthyosis should therefore be evaluated for nerve involvement.

Ipsilateral hemiparesis in ischemic stroke patients

Objectives To investigate clinical characteristics of ipsilateral hemiparesis in ischemic stroke patients. Materials and methods Patients with acute ischemic stroke were prospectively examined. Ipsilateral hemiparesis was defined as hemiparesis ipsilateral to recent stroke lesions. Patients with ipsilateral hemiparesis were examined with functional neuroimaging studies including transcranial magnetic stimulation (TMS) and functional MRI. Results Of 8360 patients, ipsilateral hemiparesis was detected in 14 patients (0.17%, mean age 71±6 years, eight men). Lesions responsible for the recent strokes were located in the frontal cortex in three patients, corona radiata in seven, internal capsule in one, and pons in three. These lesions were located along the typical route of the corticospinal tract in all but one patient. Thirteen patients also had a past history of stroke contralateral to the recent lesions; 12 of these had motor deficits contralateral to past stroke lesions. During TMS, ipsilateral magnetic evoked potentials were evoked in two of seven patients and contralateral potentials were evoked in all seven. Functional MRI activated cerebral hemispheres ipsilaterally in eight of nine patients and contralaterally in all nine. Conclusions Most patients with ipsilateral hemiparesis had a past history of stroke contralateral to the recent one, resulting in motor deficits contralateral to the earlier lesions. Moreover, functional neuroimaging findings indicated an active crossed corticospinal tract in all of the examined patients. Both findings suggest the contribution of the uncrossed corticospinal tract contralateral to stroke lesions as a post-stroke compensatory motor system.

Ipsilateral hemiparesis in ischemic stroke patients

To investigate clinical characteristics of ipsilateral hemiparesis in ischemic stroke patients. Patients with acute ischemic stroke were prospectively examined. Ipsilateral hemiparesis was defined as hemiparesis ipsilateral to recent stroke lesions. Patients with ipsilateral hemiparesis were examined with functional neuroimaging studies including transcranial magnetic stimulation (TMS) and functional MRI. Of 8360 patients, ipsilateral hemiparesis was detected in 14 patients (0.17%, mean age 71±6years, eight men). Lesions responsible for the recent strokes were located in the frontal cortex in three patients, corona radiata in seven, internal capsule in one, and pons in three. These lesions were located along the typical route of the corticospinal tract in all but one patient. Thirteen patients also had a past history of stroke contralateral to the recent lesions; 12 of these had motor deficits contralateral to past stroke lesions. During TMS, ipsilateral magnetic evoked potentials were evoked in two of seven patients and contralateral potentials were evoked in all seven. Functional MRI activated cerebral hemispheres ipsilaterally in eight of nine patients and contralaterally in all nine. Most patients with ipsilateral hemiparesis had a past history of stroke contralateral to the recent one, resulting in motor deficits contralateral to the earlier lesions. Moreover, functional neuroimaging findings indicated an active crossed corticospinal tract in all of the examined patients. Both findings suggest the contribution of the uncrossed corticospinal tract contralateral to stroke lesions as a post-stroke compensatory motor system.

Ipsilateral hemiparesis caused by putaminal hemorrhage in a patient with horizontal gaze palsy with progressive scoliosis: a case report

BackgroundHorizontal gaze palsy with progressive scoliosis (HGPPS) is an autosomal recessive disorder caused by mutations in the ROBO3 gene, resulting in a critical absence of crossing fibers in the brainstem.Case presentationWe present a patient with ipsilateral hemiparesis caused by putaminal hemorrhage who had a history of horizontal gaze paralysis and scoliosis since childhood. Diffusion tensor imaging (DTI) tractography confirmed the presence of uncrossed corticospinal tracts. Sequence analysis of the entire ROBO3 coding regions revealed a novel nonsense mutation.ConclusionWe report the first known HGPPS case with intracranial hemorrhage and ROBO3 mutation showing an absence of major crossing pathways by DTI.

Pyramidal tract abnormalities in the human fetus and infant with trisomy 18 syndrome

Trisomy 18 or Edwards syndrome is known to exhibit various developmental abnormalities in the central nervous system. We report dominant uncrossed pyramidal tract in trisomy 18 syndrome, based on the postmortem neuropathologic study of eight consecutive autopsied fetuses and infants with trisomy 18 ranging in age from 16 to 39 weeks of gestation, including six males and two females, along with autopsy cases of a stillborn triploid infant with 69XXX and two stillborn infants without chromosomal or neurodevelopmental abnormalities. Five out of eight cases with trisomy 18 showed a larger proportion of uncrossed than crossed pyramidal tract. All of these cases were male, and the anterior corticospinal tract on one side was constantly larger than the contralateral lateral corticospinal tract in the spinal cord on both sides, while the pyramidal tract was hypoplastic in female cases with trisomy 18 and a case with 69XXX. Abnormal pyramidal decussation has been found in cases with posterior fossa malformations such as occipital encephaloceles, Dandy-Walker malformation, Joubert syndrome and Möbius syndrome, but has not been described in cases with trisomy 18. Our data, together with the previous reports describing uncrossed aberrant ipsilateral pyramidal tract in patients with congenital mirror movements caused by DCC gene mutation in chromosome 18, and hypolasia and hyperplasia of the pyramidal tract in X-linked recessive disorders caused by L1CAM and Kal1 gene mutations, respectively, suggest a role of trisomy 18 in association with X-chromosome in the abnormal development of the pyramidal tract.

Brainstem Stroke: Anatomy, Clinical and Radiological Findings

Ischemic brainstem strokes constitute 10% of all ischemic brain strokes. Hemorrhagic complications are associated with an especially poor prognosis. Associated symptomatology includes vertigo, cranial nerve symptoms, and crossed or uncrossed corticospinal tract findings. Advanced neuroimaging techniques have become essential in the decision-making process of brainstem stroke management and may provide a means to identify those patients who may benefit from thrombolysis. Because many of the recommendations are based on limited data, additional research on treatment of acute brainstem stroke is needed.

Ipsilateral Stroke with Uncrossed Pyramidal Tracts and Underlying Right Internal Carotid Artery Stenosis Treated with Percutaneous Transluminal Angioplasty and Stenting

We present a unique case of ipsilateral stroke in a 55-year-old right-handed hypertensive man with proven uncrossed pyramidal tract demonstrated by tractography. Diffusion-weighted imaging disclosed small acute ischemic infarcts in the right corona radiata with MR angiography showing narrowing of the right internal carotid artery. Significant carotid stenosis of right internal carotid artery (ICA) was detected on digital subtraction angiography as the underlying cause and subsequently treated with percutananeous transluminal angioplasty and stenting with good outcome. The presence of uncrossed pyramidal tract was confirmed by diffusion tensor imaging tractography. To our knowledge there are few reports of ipsilateral stroke with proven uncrossed pyramidal tracts described in the literature. This is the first documented report of ipsilateral stroke with uncrossed fibre tracts due to underlying critical stenosis of the ICA treated successfully with a good recovery.

Ipsilateral Stroke in a Patient With Horizontal Gaze Palsy With Progressive Scoliosis and a Subcortical Infarct

horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare congenital disorder caused by mutation in the ROBO3 gene. It is characterized by absent horizontal eye movements with progressive scoliosis developing in childhood and adolescence. To our knowledge, both diffusion tensor imaging evaluation in HGPPS patients who present with stroke and truncating stop codon mutation in the ROBO3 gene have yet to be reported. we present a man with HGPPS who experienced a left pure motor stroke as a result of a left corona radiata infarct on diffusion-weighted imaging. Diffusion tensor imaging tractography confirmed the presence of uncrossed corticospinal tracts, accounting for the ipsilateral deficit. He was also found to possess a novel ROBO3 stop codon mutation on genetic testing. patients with HGPPS may present with stroke symptoms on the ipsilateral side of the infarct in view of uncrossed corticospinal tracts. Truncating mutation in ROBO3 may provide additional pathophysiologic insights.

A genetic tool to study the development and function of precerebellar neurons

Event Abstract Back to Event A genetic tool to study the development and function of precerebellar neurons Alain Chedotal1* 1 INSERM U592, Department of Development, Institut de la vision, France In bilateria, at all levels of the nervous system, axons cross the midline, dorsally or ventrally to form commissural projections. Commissures are required for coordinating sensory information received on both sides of the body but their function in other commissural systems is unclear. The molecular mechanisms regulating midline crossing are known to be highly conserved in evolution and involve primarily attractants and repellents secreted by midline cells. Human patients suffering from the «Horizontal Gaze Palsy with Progressive Scoliosis» (HGPPS) syndrome, have uncrossed pyramidal tract and dorsal column-medial lemniscus as well as defects in conjugated horizontal eye movements. However, patients are otherwise still coordinated and have no obvious neurological deficits. All HGGPS patients carry mutations in the Roundabout 3 receptor (Robo3). Existing Robo3 knockout mice lack precerebellar commissures in the hindbrain as well as ventral commissure in the spinal cord. However, Robo3-/-mice do not survive after birth for unknown reasons, and their behavior, oculomotricity, and postnatal development cannot be studied. To overcome this problem we generated a Robo3 conditional knockout (Robo3lox) that was crossed to transgenic mice expressing the Cre recombinase in precerebellar neurons. We found that wnt1-cre ;robo3lox/lox and ptf1acre ;robo3lox/lox mice have abnormal mossy fiber commissures or climbing fiber commissures respectively, as previously described in Robo3-/- embryos. This is accompanied by severe motor deficits. Conference: 3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009. Presentation Type: Oral Presentation Topic: Symposium 11 – Development of the cerebellum: from neurogenesis to axon guidance and dendritic differentiation Citation: Chedotal A (2009). A genetic tool to study the development and function of precerebellar neurons. Front. Neurosci. Conference Abstract: 3rd Mediterranean Conference of Neuroscience . doi: 10.3389/conf.neuro.01.2009.16.047 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 19 Nov 2009; Published Online: 19 Nov 2009. * Correspondence: Alain Chedotal, INSERM U592, Department of Development, Institut de la vision, Paris, France, alain.chedotal@snv.jussieu.fr Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Alain Chedotal Google Alain Chedotal Google Scholar Alain Chedotal PubMed Alain Chedotal Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Functional anatomy of motor urgency

This PET H215O study uses a reaching task to determine the neural basis of the unconscious motor speed up observed in the context of urgency in healthy subjects. Three conditions were considered: self-initiated (produce the fastest possible movement toward a large plate, when ready), externally-cued (same as self-initiated but in response to an acoustic cue) and temporally-pressing (same as externally-cued with the plate controlling an electromagnet that prevented a rolling ball from falling at the bottom of a tilted ramp). Results show that: (1) Urgent responses (Temporally-pressing versus Externally-cued) engage the left parasagittal and lateral cerebellar hemisphere and the sensorimotor cortex (SMC) bilaterally; (2) Externally-driven responses (Externally-cued versus Self-initiated) recruit executive areas within the contralateral SMC; (3) Volitional responses (Self-initiated versus Externally-cued) involve prefrontal cortical areas.These observations are discussed with respect to the idea that neuromuscular energy is set to a submaximal threshold in self-determined situations. In more challenging tasks, this threshold is raised and the first answer of the nervous system is to optimize the response of the lateral (i.e. crossed) corticospinal tract (contralateral SMC) and ipsilateral cerebellum. In a second step, the anterior (i.e. uncrossed) corticospinal tract (ipsilateral SMC) and the contralateral cerebellum are recruited. This recruitment is akin to the strategy observed during recovery in patients with brain lesions.

Uncrossed actions of feline corticospinal tract neurones on lumbar interneurones evoked via ipsilaterally descending pathways

Effects of stimulation of ipsilateral pyramidal tract (PT) fibres were analysed in interneurones in midlumbar segments of the cat spinal cord in search of interneurones mediating disynaptic actions of uncrossed PT fibres on hindlimb motoneurones. The sample included 44 intermediate zone and ventral horn interneurones, most with monosynaptic input from group I and/or group II muscle afferents and likely to be premotor interneurones. Monosynaptic EPSPs evoked by stimulation of the ipsilateral PT were found in 12 of the 44 (27%) interneurones, while disynaptic or trisynaptic EPSPs were evoked in more than 75%. Both appeared at latencies that were either longer or within the same range as those of disynaptic EPSPs and IPSPs evoked by PT stimuli in motoneurones, making it unlikely that premotor interneurones in pathways from group I and/or II afferents relay the earliest actions of uncrossed PT fibres on motoneurones. These interneurones might nevertheless contribute to PT actions at longer latencies. Uncrossed PT actions on interneurones were to a great extent relayed via reticulospinal neurones with axons in the ipsilateral medial longitudinal fascicle (MLF), as indicated by occlusion and mutual facilitation of actions evoked by PT and MLF stimulation. However, PT actions were also relayed by other supraspinal or spinal neurones, as some remained after MLF lesions. Mutual facilitation and occlusion of actions evoked from the ipsilateral and contralateral PTs lead to the conclusion that the same midlumbar interneurones in pathways from group I or II muscle afferents may relay uncrossed and crossed PT actions.

Patients with horizontal gaze palsy and progressive scoliosis due to ROBO3 E319K mutation have both uncrossed and crossed central nervous system pathways and perform normally on neuropsychological testing

Background: Horizontal gaze palsy and progressive scoliosis (HGPPS) is caused by mutations of the ROBO3 gene, which encodes a receptor associated with axonal guidance during development. Although there is evidence...

Multimodal imaging of brain reorganization in motor areas of the contralesional hemisphere of well recovered patients after capsular stroke

Clinical recovery after stroke can be significant and has been attributed to plastic reorganization and recruitment of novel areas previously not engaged in a given task. As equivocal results have been reported in studies using single imaging or electrophysiological methods, here we applied an integrative multimodal approach to a group of well-recovered chronic stroke patients (n = 11; aged 50-81 years) with left capsular lesions. Focal activation during recovered hand movements was assessed with EEG spectral analysis and H2(15)O-PET with EMG monitoring, cortico-cortical connectivity with EEG coherence analysis (cortico-cortical coherence) and corticospinal connectivity with transcranial magnetic stimulation (TMS). As seen from comparisons with age-matched controls, our patients showed enhanced recruitment of the lateral premotor cortex of the lesioned hemisphere [Brodmann area (BA) 6], lateral premotor and to a lesser extent primary sensorimotor and parietal cortex of the contralesional hemisphere (CON-H; BA 4 and superior parietal lobule) and left cerebellum (patients versus controls, Z > 3.09). EEG coherence analysis showed that after stroke cortico-cortical connections were reduced in the stroke hemisphere but relatively increased in the CON-H (ANOVA, contrast analysis, P < 0.05), suggesting a shift of functional connectivity towards the CON-H. Nevertheless, fast conducting corticospinal transmission originated exclusively from the lesioned hemisphere. No direct ipsilateral motor evoked potentials (MEPs) could be elicited with TMS over the contralesional primary motor cortex (iM1) in stroke patients. We conclude that (i) effective recovery is based on enhanced utilization of ipsi- and contralesional resources, (ii) basic corticospinal commands arise from the lesioned hemisphere without recruitment of ('latent') uncrossed corticospinal tract fibres and (iii) increased contralesional activity probably facilitates control of recovered motor function by operating at a higher-order processing level, similar to but not identical with the extended network concerned with complex movements in healthy subjects.

Partially Uncrossed Pyramidal Tracts Shown by Tractography in Horizontal Gaze Palsy and Scoliosis

Mori H, Fijishiro T, Hayashi N, Masutani Y, Aoki S, Ohtomo K, Aihara M, Wakakura M(AQ1) ongenital defects of the midline structures of the brainstem in the absence of disorders of the cerebellum are rare [1–4]. The primary clinical finding is the restriction of bilateral horizontal gaze. Brainstem morphology suggests a defect associated with pyramidal decussation; however, relatively few reports have shown this characteristic via transcranial magnetic stimulation, functional MRI, and sensory evoked potentials [1]. We describe a patient with sporadic isolated horizontal gaze palsy and scoliosis in whom tractography revealed partially uncrossed pyramidal tracts.

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Alteraciones en el movimiento tras accidente cerebrovascular en el hemicuerpo ipsilateral al hemisferio cerebral lesionado

We analyze the explanatory hypotheses proposed in most relevant studies on the different altered movements (AM) in the unaffected part of the body following a stroke. We report 25 cases of AM patients whose clinical signs do not correspond with the AM described in previous studies. A possible explanation could be established from a different neuroplastic hypothesis. To review the main hypotheses which try to explain the presence of AM in the part of the body ipsilesional to the injured hemisphere of the brain. To this end we overview some updated studies concerning the corticospinal tract function, and the neuroplastic capacity after a stroke. Simultaneously, we study 25 cases of patients with cerebrovascular disease and some clinical findings which present a different type of AM from those previously reported. Motor alterations described in most studies concerning stroke patients correspond well to a diminished selectivity of movements of the unaffected hand, to associated movements in both upper limbs or to mirror movements. Explanations of these hypothesis are: the effect of injured fibres of the uncrossed corticospinal tract and neuroplastic reorganization of the ipsilateral pathways. The existence of different AM is observed in some clinical cases which we found to be scarcely studied in published research. These movements appear in the non-affected part of the body throughout cerebrovascular disease evolution, and which could be caused by maintained hypersolicitation of the unaffected part of the body and the neuroplastic process following a stroke. Further functional neuroimaging investigations are needed to confirm this clinical hypothesis.

Development and malformations of the human pyramidal tract

The corticospinal tract develops over a rather long period of time, during which malformations involving this main central motor pathway may occur. In rodents, the spinal outgrowth of the corticospinal tract occurs entirely postnatally, but in primates largely prenatally. In mice, an increasing number of genes have been found to play a role during the development of the pyramidal tract. In experimentally studied mammals, initially a much larger part of the cerebral cortex sends axons to the spinal cord, and the site of termination of corticospinal fibers in the spinal grey matter is much more extensive than in adult animals. Selective elimination of the transient corticospinal projections yields the mature projections functionally appropriate for the pyramidal tract. Direct corticomotoneuronal projections arise as the latest components of the corticospinal system. The subsequent myelination of the pyramidal tract is a slow process, taking place over a considerable period of time. Available data suggest that in man the pyramidal tract develops in a similar way. Several variations in the funicular trajectory of the human pyramidal tract have been described in otherwise normally developed cases, the most obvious being those with uncrossed pyramidal tracts. A survey of the neuropathological and clinical literature, illustrated with autopsy cases, reveals that the pyramidal tract may be involved in a large number of developmental disorders. Most of these malformations form part of a broad spectrum, ranging from disorders of patterning, neurogenesis and neuronal migration of the cerebral cortex to hypoxic-ischemic injury of the white matter. In some cases, pyramidal tract malformations may be due to abnormal axon guidance mechanisms. The molecular nature of such disorders is only beginning to be revealed.