Ipsilateral Corticospinal Tract Research Articles

A comparative study of diffusion kurtosis imaging and diffusion tensor imaging in detecting corticospinal tract impairment in diffuse glioma patients.

This study aimed to investigate the diagnostic performance of diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) in identifying aberrations in the corticospinal tract (CST), whilst elucidating the relationship between abnormalities of CST and patients' motor function. Altogether 21 patients with WHO grade II or grade IV glioma were enrolled and divided into Group 1 and Group 2, according to the presence or absence of preoperative paralysis. DKI and DTI metrics were generated and projected onto the CST. Histograms of the CST along x, y, and z axes were developed based on DKI and DTI metrics, and compared subsequently to determine regions of aberrations on the fibers. The receiver operating characteristic curve was performed to investigate the diagnostic efficacy of DKI and DTI metrics. In Group 1, a significantly lower fractional anisotropy, radial kurtosis and mean kurtosis, and a higher mean diffusivity were found in the ipsilateral CST as compared to the contralateral CST. Significantly higher relative axial diffusivity, relative radial diffusivity, and relative mean diffusivity (rMD) were found in Group 1, as compared to Group 2. The relative volume of ipsilateral CST abnormalities higher than the maximum value of mean kurtosis combined with rMD exhibited the best diagnostic performance in distinguishing dysfunction of CST with an AUC of 0.93. DKI is sensitive in detecting subtle changes of CST distal from the tumor. The combination of DKI and DTI is feasible for evaluating the impairment of the CST.

Task-dependent alteration of beta-band intermuscular coherence is associated with ipsilateral corticospinal tract excitability.

Beta-band (15-30 Hz) synchronization between the EMG signals of active limb muscles can serve as a non-invasive assay of corticospinal tract integrity. Tasks engaging a single limb often primarily utilize one corticospinal pathway, although bilateral neural circuits can participate in goal-directed actions involving multi-muscle coordination and utilization of feedback. Suboptimal utilization of such circuits after CNS injury can result in unintended mirror movements and activation of pathological synergies. Accordingly, it is important to understand how the actions of one limb (e.g., a less-affected limb after strokes) influence the opposite corticospinal pathway for the rehabilitation target. Certain unimanual actions decrease the excitability of the "unengaged" corticospinal tract, presumably to prevent mirror movement, but there is no direct way to predict the extent to which this will occur. In this study, we tested the hypothesis that task-dependent changes in beta-band drives to muscles of one hand will inversely correlate with changes in the opposite corticospinal tract excitability. Ten participants completed spring pinching tasks known to induce differential 15-30 Hz drive to muscles. During compressions, transcranial magnetic stimulation single pulses to the ipsilateral M1 were delivered to generate motor-evoked potentials in the unengaged hand. The task-induced changes in ipsilateral corticospinal excitability were inversely correlated with associated changes in EMG-EMG coherence of the task hand. These results demonstrate a novel connection between intermuscular coherence and the excitability of the "unengaged" corticospinal tract and provide a springboard for further mechanistic studies of unimanual tasks of varying difficulty and their effects on neural pathways relevant to rehabilitation.

Mirror movements and brain pathology in children with unilateral cerebral palsy.

We systematically examined the relationship between mirror movements and brain lesion type, corticospinal tract (CST) organization, and hand function to determine the relevance between mirror movements, brain lesion, the CST pattern, and hand function in children with unilateral cerebral palsy (CP). Forty-eight children (mean age 9y 9mo[SD 3y 3mo], range 6-18y; 30 males, 18 females) with unilateral CP participated. Mirror movements, brain lesion type, CST pattern identified by transcranial magnetic stimulation, and clinical outcomes were evaluated. Children performed four unilateral tasks: hand opening/closing, finger opposition, individuation, and finger 'walking'. Mirror movements induced in the contralateral hand were scored using standardized criteria (scores 0-4 using the Woods and Teuber scale). We found that children with periventricular lesion may have stronger mirror movement scores induced in either hand than those with middle cerebral artery lesion (more affected hand: p=0.02; less affected hand: p<0.01). The highest mirror movement score a child exhibits across the tested tasks (i.e. scores of 3-4 using the Woods and Teuber scoring criteria) may potentially be an indicator of an ipsilateral CST connectivity pattern (p=0.03). Significant correlations were observed between higher mirror movement scores when performing hand opening/closing as well as finger walking and better unimanual dexterity (Spearman's rank correlation coefficient rs =0.44, p=0.002; rs =0.46, p=0.002 respectively). Brain lesions may be predictive of the strength of mirror movements in either hand in children with unilateral CP. Our findings warrant further studies to extensively investigate the relationship between mirror movements and the underlying brain pathology. Brain lesion type may be predictive of mirror movement scores induced in either hand in children with unilateral cerebral palsy. The highest mirror movement score a child exhibits across the tested tasks may indicate corticospinal tract connectivity pattern in children with unilateral cerebral palsy.

Altered cortical activation associated with mirror overflow driven by non-dominant hand movement in attention-deficit/hyperactivity disorder

Mirror overflow is involuntary movement that accompanies unilateral voluntary movement on the opposite side of the body, and is commonly seen in Attention-Deficit/Hyperactivity Disorder (ADHD). Children with ADHD show asymmetry in mirror overflow between dominant and non-dominant hand, yet there are competing mechanistic accounts of why this occurs. Using EEG during a sequential, unimanual finger-tapping task, we found that children with ADHD exhibited significantly more mirror overflow than typically developing (TD) controls, especially during the tapping of the non-dominant hand. Furthermore, source-level EEG oscillation analysis revealed that children with ADHD showed decreased alpha (8–12 Hz) event-related desynchronization (ERD) compared with controls in both hemispheres, but only during tapping of the non-dominant hand. Moreover, only the ERD ipsilateral to the mirror overflow during non-dominant hand movement correlated with both magnitude of overflow movements and higher ADHD symptom severity (Conners ADHD Hyperactivity/Impulsiveness scale) in children with ADHD. TD controls did not show these relationships. Our findings suggest that EEG differences in finger-tapping in ADHD are related primarily to voluntary movement in the non-dominant hand. Our results are also consistent with the Ipsilateral Corticospinal Tract (CST) Hypothesis, which posits that the atypical persistence of mirror overflow in ADHD may originate in the sensorimotor areas ipsilateral to mirror overflow and be transmitted via non-decussating CST fibers.

Contralateral Axon Sprouting but Not Ipsilateral Regeneration Is Responsible for Spontaneous Locomotor Recovery Post Spinal Cord Hemisection

Spinal cord injury (SCI) usually results in permanent functional impairment and is considered a worldwide medical problem. However, both motor and sensory functions can spontaneously recover to varying extents in humans and animals with incomplete SCI. This study observed a significant spontaneous hindlimb locomotor recovery in Sprague-Dawley rats at four weeks after post-right-side spinal cord hemisection at thoracic 8 (T8). To verify whether the above spontaneous recovery derives from the ipsilateral axonal or neuronal regeneration to reconnect the lesion site, we resected either the scar tissue or right side T7 spinal cord at five weeks post-T8 hemisected injury. The results showed that the spontaneously achieved right hindlimb locomotor function had little change after resection. Furthermore, when T7 left hemisection was performed five weeks after the initial injury, the spontaneously achieved right hindlimb locomotor function was dramatically abolished. A similar result could also be observed when T7 transection was performed after the initial hemisection. The results indicated that it might be the contralateral axonal remolding rather than the ipsilateral axonal or neuronal regeneration beyond the lesion site responsible for the spontaneous hindlimb locomotor recovery. The immunostaining analyses and corticospinal tracts (CSTs) tracing results confirmed this hypothesis. We detected no substantial neuronal and CST regeneration throughout the lesion site; however, significantly more CST fibers were observed to sprout from the contralateral side at the lumbar 4 (L4) spinal cord in the hemisection model rats than in intact ones. In conclusion, this study verified that contralateral CST sprouting, but not ipsilateral CST or neuronal regeneration, is primarily responsible for the spontaneous locomotor recovery in hemisection SCI rats.

Endoscopic Surgery for Supratentorial Deep Cavernous Malformation Adjacent to Cortical Spinal Tract: Preliminary Experience and Technical Note.

In this study, we aimed to introduce a technical note and to explore the efficacy of endoscopic surgery combined with diffusion tensor imaging (DTI) navigation for supratentorial deep cerebral cavernous malformations (CCM). A prospectively maintained database of CCM patients was reviewed to identify all CCM patients treated by endoscopic surgery. The sagittal T1-weighted anatomical magnetic resonance imaging (MRI) and DTI were acquired before surgery. Endoscopic surgery was planned and performed based on preoperative DTI images and intraoperative DTI navigation. All patients were followed up more than 6 months. Motor function deficit and modified Rankin scale (mRS) scores were documented on follow-up. A final mRS score of 0–2 was considered a good outcome, and a final mRS score >2 was considered a poor outcome. Second DTI and 3DT1 were performed at 3 months after surgery. We tracked the ipsilateral corticospinal tract (CST) on pre- and postoperative DTI images. The overall mean FA values and the number of fibers of tracked CST were compared on pre- and postoperative DTI images. Risk factors associated with motor deficits and poor outcomes were analyzed. Seven patients with deep CCM and treated by endoscopic surgery were enrolled in this study. The mean value of preoperative mRS was 1.5 ± 0.98, but that score recovered to 0.86 ± 1.22 3 months later. The mRS scores were improved significantly according to statistical analysis (p = 0.012). According to the Spearman non-parametric test, only the fiber number of ipsilateral CST on postoperative DTI was significantly associated with muscle strength 6 months after surgery (p = 0.032). Compared with preoperative CST characteristics on DTI, the change of FA value (p = 0.289) and fiber number (p = 0.289) of ipsilateral CST on postoperative DTI was not significant It meant that the CST was protected during endoscopic surgery. Endoscopic surgery based on DTI navigation might be an effective method to protect fiber tracts in supratentorial deep CCM patients and improve long-term outcomes. However, more studies and cases are needed to confirm our findings.

Improvements in Upper Extremity Function Following Intensive Training Are Independent of Corticospinal Tract Organization in Children With Unilateral Spastic Cerebral Palsy: A Clinical Randomized Trial.

Background/Objectives: Intensive training of the more affected upper extremity (UE) has been shown to be effective for children with unilateral spastic cerebral palsy (USCP). Two types of UE training have been particularly successful: Constraint-Induced Movement Therapy (CIMT) and Bimanual training. Reorganization of the corticospinal tract (CST) early during development often occurs in USCP. Prior studies have suggested that children with an ipsilateral CST controlling the affected UE may improve less following CIMT than children with a contralateral CST. We tested the hypothesis that improvements in UE function after intensive training depend on CST laterality.Study Participants and Setting: Eighty-two children with USCP, age 5 years 10 months to 17 years, University laboratory setting.Materials/Methods: Single-pulse transcranial magnetic stimulation (TMS) was used to determine each child's CST connectivity pattern. Children were stratified by age, sex, baseline hand function and CST connectivity pattern, and randomized to receive either CIMT or Bimanual training, each of which were provided in a day-camp setting (90 h). Hand function was tested before, immediately and 6 months after the intervention with the Jebsen-Taylor Test of Hand Function, the Assisting Hand Assessment, the Box and Block Test, and ABILHAND-Kids. The Canadian Occupational Performance Measure was used to track goal achievement and the Pediatric Evaluation of Disability Inventory was used to assess functioning in daily living activities at home.Results: In contrast to our hypothesis, participants had statistically similar improvements for both CIMT and Bimanual training for all measures independent of their CST connectivity pattern (contralateral, ipsilateral, or bilateral) (p < 0.05 in all cases).Conclusions/Significance: The efficacy of CIMT and Bimanual training is independent of CST connectivity pattern. Children with an ipsilateral CST, previously thought to be maladaptive, have the capacity to improve as well as children with a contralateral or bilateral CST following intensive CIMT or Bimanual training.Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02918890.

Constraint-induced intervention as an emergent phenomenon from synaptic competition in biological systems

The principle of constraint-induced therapy is widely practiced in rehabilitation. In hemiplegic cerebral palsy (CP) with impaired contralateral corticospinal projection due to unilateral injury, function improves after imposing a temporary constraint on limbs from the less affected hemisphere. This type of partially-reversible impairment in motor control by early brain injury bears a resemblance to the experience-dependent plastic acquisition and modification of neuronal response selectivity in the visual cortex. Previously, such mechanism was modeled within the framework of BCM (Bienenstock-Cooper-Munro) theory, a rate-based synaptic modification theory. Here, we demonstrate a minimally complex yet sufficient neural network model which provides a fundamental explanation for inter-hemispheric competition using a simplified spike-based model of information transmission and plasticity. We emulate the restoration of function in hemiplegic CP by simulating the competition between cells of the ipsilateral and contralateral corticospinal tracts. We use a high-speed hardware neural simulation to provide realistic numbers of spikes and realistic magnitudes of synaptic modification. We demonstrate that the phenomenon of constraint-induced partial reversal of hemiplegia can be modeled by simplified neural descending tracts with 2 layers of spiking neurons and synapses with spike-timing-dependent plasticity (STDP). We further demonstrate that persistent hemiplegia following unilateral cortical inactivation or deprivation is predicted by the STDP-based model but is inconsistent with BCM model. Although our model is a highly simplified and limited representation of the corticospinal system, it offers an explanation of how constraint as an intervention can help the system to escape from a suboptimal solution. This is a display of an emergent phenomenon from the synaptic competition.

Prediction of Motor Recovery after Stroke by Assessment of Corticospinal Tract Wallerian Degeneration Using Diffusion Tensor Imaging.

Aim of the Study To predict motor recovery after stroke by detection of diffusion tensor imaging (DTI) fractional anisotropy (FA) changes of corticospinal tract (CST) and correlate findings with clinical scores to provide more effective treatment and rehabilitation. Subjects and Methods Thirty patients with cerebral stroke were enrolled and underwent conventional magnetic resonance imaging and DTI at admission and 1 month after stroke. Mean diffusivity (MD), FA, FA ratio (rFA), and fiber number (FN) values of CST were calculated at the pons at admission and after 1 month of stroke. Three-dimensional reconstruction of bilateral CST and the structural changes of fibrous bands were observed. Severity of limb weakness was assessed by using the motor sub-index scores of the National Institutes of Health Stroke Scale (NIHSS) at admission, and after 1, 6, and 9 months for severity of limb weakness. Results The mean age of our patients was 61.32 ± 4.34 years, 17/30 (56.6%) were females, and 13/30 (43.4%) were males. In our study, 18/30 (60%) were hypertensive, 19/30 (63.3%) were diabetic, and 12/30 (40%) were smokers. A significant negative correlation was found between rFA and FN in the ipsilateral CST of the cerebral infarction at the rostral part of pons after 1 month of infarction and NIHSS score at 6 months ( r = 0.377, p = 0.04 and r = 0.237, p = 0.02, respectively). However, a positive insignificant correlation was found between MD and NIHSS ( r = 0.345, p = 0.635). The initial NIHSS score at the time of injury was 19.2 ± 4.3, which changed to 7.9 ± 2.4, 4.6 ± 1.9, and 3.3 ± 1.4 at 1, 6, and 9 months, respectively. Conclusion DTI is a sensitive tool for early detection of Wallerian degeneration in the CST after stroke, and can predict motor performance to provide effective treatment and rehabilitation to improve quality of life.

Utility of a Quantitative Approach Using Diffusion Tensor Imaging for Prognostication Regarding Motor and Functional Outcomes in Patients With Surgically Resected Deep Intracranial Cavernous Malformations.

Resection of deep intracranial cavernous malformations (CMs) is associated with a higher risk of neurological deterioration and uncertainty regarding clinical outcomes. To examine diffusion tractography imaging (DTI) data evaluating the corticospinal tract (CST) in relation to motor and functional outcomes in patients with surgically resected deep CMs. Perilesional CST was characterized as disrupted, displaced, or normal. Mean fractional anisotropy (FA) values were obtained for whole ipsilateral CST and in 3 regions: subcortical (proximal), perilesional, and distally. Mean FA values in anatomically equivalent regions in the contralateral CST were obtained. Clinical and radiological data were collected independently. Multivariable regression analysis was used for statistical analysis. A total of 18 patients [brainstem (15) and thalamus/basal ganglia (3); median follow-up: 270 d] were identified over 2 yr. The CST was identified preoperatively as disrupted (6), displaced (8), and normal (4). Five of 6 patients with disruption had weakness. Higher preoperative mean FA values for distal ipsilateral CST segment were associated with better preoperative lower (P<.001), upper limb (P=.004), postoperative lower (P=.005), and upper limb (P<.001) motor examination. Preoperative mean FA values for distal ipsilateral CST segment (P=.001) and contralateral perilesional CST segment (P<.001) were negatively associated with postoperative modified Rankin scale scores. Lower preoperative mean FA values for overall and defined CST segments corresponded to worse patient pre- and postoperative motor examination and/or functional status. FA value for the distal ipsilateral CST segment has prognostic potential with respect to clinical outcomes.

White matter characteristics of motor, sensory and interhemispheric tracts underlying impaired upper limb function in children with unilateral cerebral palsy.

This study explored the role of lesion timing (periventricular white matter versus cortical and deep grey matter lesions) and type of corticospinal tract (CST) wiring pattern (contralateral, bilateral, ipsilateral) on white matter characteristics of the CST, medial lemniscus, superior thalamic radiations and sensorimotor transcallosal fibers in children with unilateral cerebral palsy (CP), and examined theassociation with upper limb function. Thirty-four children (mean age 10 years 7 months ± 2 years 3 months) with unilateral CP underwent a comprehensive upper limb evaluation and diffusion weighted imaging (75 directions, b value 2800). Streamline count, fractional anisotropy and mean diffusivity were extracted from the targeted tracts and asymmetry indices were additionally calculated. Transcranial magnetic stimulation was applied to assess the CST wiring pattern. Results showed a more damaged CST in children with cortical and deep grey matter lesions (N = 10) and ipsilateral CST projections (N = 11) compared to children with periventricular white matter lesions (N = 24; p < 0.02) and contralateral CST projections (N = 9; p < 0.025), respectively. Moderate to high correlations were found between diffusion metrics of the targeted tracts and upper limb function (r = 0.45-0.72; p < 0.01). Asymmetry indices of the CST and sensory tracts could best explain bimanual performance (74%, p < 0.0001) and unimanual capacity (50%, p = 0.004). Adding lesion timing and CST wiring pattern did not further improve the model of bimanual performance, while for unimanual capacity lesion timing was additionally retained (58%, p = 0.0002). These results contribute to a better understanding of the underlying neuropathology of upper limb function in children with unilateral CP and point towards a clinical potential of tractography.

The value of diffusion tensor tractography delineating corticospinal tract in glioma in rat: validation via correlation histology.

BackgroundAn assessment of the degree of white matter tract injury is important in neurosurgical planning for patients with gliomas. The main objective of this study was to assess the injury grade of the corticospinal tract (CST) in rats with glioma using diffusion tensor imaging (DTI).MethodsA total 17 rats underwent 7.0T MRI on day 10 after tumor implantation. The apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were acquired in the tumor, peritumoral and contralateral areas, and the ADC ratio (ipsilateral ADC/contralateral ADC) and rFA (relative FA = ipsilateral FA/contralateral FA) in the peritumoral areas were measured. The CST injury was divided into three grades and delineated by diffusion tensor tractography reconstruction imaging. The fiber density index (FDi) of the ipsilateral and contralateral CST and rFDi (relative FDi = ipsilateral FDi/contralateral FDi) in the peritumoral areas were measured. After the mice were sacrificed, the invasion of glioma cells and fraction of proliferating cells were observed by hematoxylin-eosin and Ki67 staining in the tumor and peritumoral areas. The correlations among the pathology results, CST injury grade and DTI parameter values were calculated using a Spearman correlation analysis. One-way analysis of variance was performed to compare the different CST injury grade by the rFA, rFDi and ADC ratio values.ResultsThe tumor cells and proliferation index were positively correlated with the CST injury grade (r = 0.8857, 0.9233, P < 0.001). A negative correlation was demonstrated between the tumor cells and the rFA and rFDi values in the peritumoral areas (r = −0.8571, −0.5588), and the proliferation index was negatively correlated with the rFA and rFDi values (r = −0.8571, −0.5588), while the ADC ratio was not correlated with the tumor cells or proliferation index. The rFA values between the CST injury grades (1 and 3, 2 and 3) and the rFDi values in grades 1 and 3 significantly differed (P < 0.05).ConclusionsDiffusion tensor imaging may be used to quantify the injury degrees of CST involving brain glioma in rats. Our data suggest that these quantitative parameters may be used to enhance the efficiency of delineating the relationship between fiber tracts and malignant tumor.

Neural function in DCC mutation carriers with and without mirror movements.

ObjectiveRecently identified mutations of the axon guidance molecule receptor gene, DCC, present an opportunity to investigate, in living human brain, mechanisms affecting neural connectivity and the basis of mirror movements, involuntary contralateral responses that mirror voluntary unilateral actions. We hypothesized that haploinsufficient DCC +/− mutation carriers with mirror movements would exhibit decreased DCC mRNA expression, a functional ipsilateral corticospinal tract, greater “mirroring” motor representations, and reduced interhemispheric inhibition. DCC +/− mutation carriers without mirror movements might exhibit some of these features.MethodsThe participants (n = 52) included 13 DCC +/− mutation carriers with mirror movements, 7 DCC +/− mutation carriers without mirror movements, 13 relatives without the mutation or mirror movements, and 19 unrelated healthy volunteers. The multimodal approach comprised quantitative real time polymerase chain reaction, transcranial magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI) under resting and task conditions, and measures of white matter integrity.ResultsMirror movements were associated with reduced DCC mRNA expression, increased ipsilateral TMS‐induced motor evoked potentials, increased fMRI responses in the mirroring M1 and cerebellum, and markedly reduced interhemispheric inhibition. The DCC +/− mutation, irrespective of mirror movements, was associated with reduced functional connectivity and white matter integrity.InterpretationDiverse connectivity abnormalities were identified in mutation carriers with and without mirror movements, but corticospinal effects and decreased peripheral DCC mRNA appeared driven by the mirror movement phenotype. ANN NEUROL 2019;85:433–442.

Abstract WP142: 18 F-THK5351 PET Imaging of Wallerian Degeneration of the Pyramidal Tract in a Post-Stroke Patient: A Longitudinal Case Study

Introduction: The PET radioligand, 18 F-THK5351, was initially developed to target tau aggregation present in neurofibrillary tangles. However, 18 F-THK5351 was recently reported to bind to monoamine oxidase B (MAO-B) with a certain level of affinity. MAO-B is highly concentrated in astrocytes. MAO-B concentration increases during so-called "gliosis", which is a spectrum of changes in astrocytes that occur after brain injury. Wallerian degeneration of the pyramidal tract usually develops after a cerebral infarction including primary motor cortex. In the early stage, axonal swelling and breakdown of myelin sheath occur. In the later stage, the degenerated axons are replaced by gliosis, which is primarily the proliferation of astrocytes to form a scar. These suggest that 18 F-THK5351 concentrates in the lesion where gliosis occurs in the process of Wallerian degeneration. We now present a case showing a potential use of 18 F-THK5351 PET to identify Wallerian degeneration of the pyramidal tract after a cerebral infarction. Methods: A patient developed left-sided hemiplegia caused by a right middle cerebral artery infarction at the age of 39, and underwent 18 F-THK5351 PET at ages 41 and 42. Emission data were acquired for 20 min starting at 40 min after an intravenous injection of 18 F-THK5351. Images were normalized using the cerebellum as a reference region Results: 18 F-THK5351 images at ages 41 and 42 showed intense uptake along the ipsilateral pyramidal tract from the corona radiata to the medulla (Figure 1, arrows). 18 F-THK5351 uptake slightly decreased at the age of 42. Conclusion: 18 F-THK5351 PET can identify Wallerian degeneration of the pyramidal tract accompanied with gliosis by targeting MAO-B located. This case suggests that gliosis in the process of Wallerian degeneration of the pyramidal tract still remains even three years after the stroke. Figure1: MRI (A) and 18 F-THK5351 images superimposed on MRI at ages 41 (B) and 42 (C)

Mirror movements in children with unilateral cerebral palsy due to perinatal stroke: clinical correlates of plasticity reorganization.

We aimed to determine if the mirror movements that often result in children with unilateral cerebral palsy (CP) after perinatal stroke represent a clinical biomarker of developmental plasticity. This was a prospective, controlled cohort study. Mirror movements in children with unilateral CP from a population-based cohort were compared to those of typically developing controls. The population with stroke was assessed further via electromyography (EMG), motor function, and corticospinal organization investigations. Mirror movements were quantified (0-5) bidirectionally. EMG mirror movements were quantified during voluntary contraction. Motor function was quantified by validated measures including the Assisting Hand Assessment (AHA). Corticospinal organization was categorized as ipsilateral or contralateral using transcranial magnetic stimulation (TMS). The relationships between mirror movements, function, and corticospinal organization were assessed (t-tests, Pearson rank correlation coefficients). Ninety-two participants were scored (55 males, 37 females, mean [SD] 12y [5y 6mo], range 4-17y), 63 with complete motor outcomes and 39 with TMS data. EMG ratios correlated with clinical mirror movements (r=0.562, p=0.008). Mild mirror activity in controls declined with age (r=-0.459, p<0.001). Mirroring was stronger with tasks performed by the affected hand (p<0.001). Mirror movements correlated with AHA scores (r=-0.255, p=0.04) and poor motor outcome (p<0.001). Unaffected hand mirror activity was higher in children with ipsilateral corticospinal tract arrangements (p<0.001). Clinical mirror movements correlate with disability and corticospinal organization in children with unilateral CP with perinatal stroke. This simple bedside biomarker could facilitate patient selection for personalized rehabilitation. Mirror movements are a clinical indicator of corticospinal organization in children with unilateral cerebral palsy with perinatal stroke. Mirroring is strongest in children with ipsilateral corticospinal tract reorganization. The concept of a 'directionality factor' to mirror movements highlights additional, clinically relevant functional correlations.

Whole Brain White Matter Microstructure and Upper Limb Function: Longitudinal Changes in Fractional Anisotropy and Axial Diffusivity in Post-Stroke Patients.

Background:Diffusion tensor imaging (DTI) magnetic resonance imaging (MRI) measuring fractional anisotropy (FA) and axial diffusivity (AD) may be a useful biomarker for monitoring changes in white matter after stroke, but its associations with upper-limb motor recovery have not been well studied. We aim to describe changes in the whole-brain FA and AD in five post-stroke patients in relation to kinematic measures of elbow flexion to better understand the relationship between FA and AD changes and clinico-kinematic measures of upper limb motor recovery.Methods:We performed DTI MRI at two timepoints during the acute phase of stroke, measuring FA and AD across 48 different white matter tract regions in the brains of five hemiparetic patients with infarcts in the cortex, pons, basal ganglia, thalamus, and corona radiata. We tracked the progress of these patients using clinical Fugl-Meyer Assessments and kinematic measures of elbow flexion at the acute phase within 14 (mean: 9.4 ± 2.49) days of stroke symptom onset and at a follow-up appointment 2 weeks later (mean: 16 ± 1.54) days.Results:Changes in FA and AD in 48 brain regions occurring during stroke rehabilitation are described in relation to motor recovery. In this case series, one patient with a hemipontine infarct showed an increase in FA of the ipsilateral and contralateral corticospinal tract, whereas other patients with lesions involving the corona radiata and middle cerebral artery showed widespread decreases in perilesional FA. On the whole, FA and AD seemed to behave inversely to each other.Conclusions:This case series describes longitudinal changes in perilesional and remote FA and AD in relation to kinematic parameters of elbow flexion at the subacute post-stroke period. Although studies with larger sample sizes are needed, our findings indicate that longitudinally measured changes in DTI-based measurements of white matter microstructural integrity may aid in the prognostication of patients affected by motor stroke.

Corticospinal Tract Wiring and Brain Lesion Characteristics in Unilateral Cerebral Palsy: Determinants of Upper Limb Motor and Sensory Function.

Brain lesion characteristics (timing, location, and extent) and the type of corticospinal tract (CST) wiring have been proposed as determinants of upper limb (UL) motor function in unilateral cerebral palsy (uCP), yet an investigation of the relative combined impact of these factors on both motor and sensory functions is still lacking. Here, we first investigated whether structural brain lesion characteristics could predict the underlying CST wiring and we explored the role of CST wiring and brain lesion characteristics to predict UL motor and sensory functions in uCP. Fifty-two participants with uCP (mean age (SD): 11 y and 3 m (3 y and 10 m)) underwent a single-pulse Transcranial Magnetic Stimulation session to determine CST wiring between the motor cortex and the more affected hand (n = 17 contralateral, n = 19 ipsilateral, and n = 16 bilateral) and an MRI to determine lesion timing (n = 34 periventricular (PV) lesion, n = 18 corticosubcortical (CSC) lesion), location, and extent. Lesion location and extent were evaluated with a semiquantitative scale. A standardized protocol included UL motor (grip strength, unimanual capacity, and bimanual performance) and sensory measures. A combination of lesion locations (damage to the PLIC and frontal lobe) significantly contributed to differentiate between the CST wiring groups, reclassifying the participants in their original group with 57% of accuracy. Motor and sensory functions were influenced by each of the investigated neurological factors. However, multiple regression analyses showed that motor function was predicted by the CST wiring (more preserved in individuals with contralateral CST (p < 0.01)), lesion extent, and damage to the basal ganglia and thalamus. Sensory function was predicted by the combination of a large and later lesion and an ipsilateral or bilateral CST wiring, which led to increased sensory deficits (p < 0.05). These novel insights contribute to a better understanding of the underlying pathophysiology of UL function and may be useful to delineate individualized treatment strategies.

Síndrome de Opalski

El síndrome de Opalski es la presencia de hemiplejia ipsilateral asociada con síntomas del síndrome medular lateral. Diferentes estudios confirman que el infarto en tales casos ocurre a un nivel más bajo que el encontrado en el síndrome de Wallenberg. Se localiza debido a la presentación característica, el territorio único de suministro de sangre y el área pequeña de lesión. La implicación del tracto corticoespinal ipsilateral después de la decusación piramidal, o compresión de la decusación, podrían causarlo. Presentamos el caso de una mujer de 71 años que desarrolló hemiplejia izquierda y dificultad repentina para caminar, acompañada de diplopía, cefalea, disfagia y vómito recurrente. La imagen de resonancia magnética demostró un infarto lateral medular izquierdo. La angiografía reveló estenosis distal y proximal de la arteria vertebral izquierda e hipoplasia de la arteria vertebral derecha.

Congenital Mirror Movements: Behavioral, Neural, Genetic, and Clinical Issues

Non-syndromic congenital mirror movements (CMM) is a rare neurological condition, either inherited or sporadic, in which affected individuals lack independent dexterity of hand and finger movements. With all volitional movements of the hands and fingers, unintentional mirroring occurs in the opposite-side homologous effectors. A hallmark neural mechanism of CMM is abnormal, active, extra ipsilateral corticospinal tracts. Mutations in four different causal genes have been identified so far. The present review considers the physiology underlying CMM, including its implicated neural mechanisms and clinical relevance. The heterogeneous nature of the condition is highlighted, particularly in terms of the clinical importance of factors associated with the mirroring phenotype or phenotypes. Speculation about the possible effects of CMM on the somatosensory system is also included as a prospective direction for further study. Despite some inconvenience and occasional discomfort associated with CMM, the potential for highly positive life outcomes is illuminated. Lastly, CMM management is discussed as a key goal toward which future research should stride.

Thermal Stimulation Changes Diffusivity of the Spinothalamic Tract

Study Design.An experimental study.Objective.This study aimed to investigate task-dependent changes in fractional anisotropy (FA) within the spinal cord during painful stimulation.Summary of Background Data.Earlier experiments by Mandl et al (2008, 2013) used non-invasive functional diffusion tensor imaging (fDTI) to detect white matter fibers that were active during functional tasks. In two studies, it was observed that FA of involved white matter tracts exhibited repeatable task-related increases. In this study, we attempted to extend the fDTI work in the spinal cord.Methods.Twenty-three healthy, right-handed men (mean age 22 yrs, standard deviation [SD] = 4) were invited to participate in this study. Diffusion-weighted images were collected over spinal levels C2 to T4 during a painful thermal stimulus applied to the left thenar eminence. In order to investigate task-related activity, FA values within the contralateral (right) spinothalamic tract were analyzed using a generalized estimating equations (GEE) procedure. As a control, we also examined activity in the ipsilateral and contralateral corticospinal tracts, which are not considered to be involved in nociception.Results.Significant task-related decreases in FA were observed in the right spinothalamic tract at vertebral levels C2–C5 (Wald X2(1) = 17.754, P < 0.001). There was no change in control regions at levels C7–T2 of the same tract, which are located below the level of input from dermatome C6, Wald X2(1) = 0.185, P = 0.667. Results in all other regions assessed, that is, the left spinothalamic tract and bilateral corticospinal tract, were also not significant (P > 0.05).Conclusion.The current findings suggest that task-related changes in FA associated with the transmission of pain signals along the spinal cord can be detected using fDTI. We observed decreased FA values in the contralateral (right) spinothalamic tract following painful stimulation, while no such activity was apparent in control regions.Level of Evidence: 5