Motor Scores Research Articles

Lesion characteristics are associated with bowel, bladder, and overall independence following cervical spinal cord injury

Context/Objective There is a growing global interest in quantifying spinal cord lesions and spared neural tissue using magnetic resonance imaging (MRI) in individuals with spinal cord injury (SCI). The primary objective of this study was to assess the relationships between spinal cord lesion characteristics assessed on MRI and bowel, bladder, and overall independence following SCI. Design Retrospective, exploratory study. Participants 93 individuals with cervical SCI who were enrolled in a local United States Model Systems SCI database from 2010 to 2017. Methods Clinical and MRI data were obtained for potential participants, and MRIs of eligible participants were analyzed. Explanatory variables, captured on MRIs, included intramedullary lesion length (IMLL), midsagittal ventral tissue bridge width (VTBW), midsagittal dorsal tissue bridge width (DTBW), and axial damage ratio (ADR). Outcome Measures Bowel and bladder management scale of the Functional Independence Measure (FIM) and FIM total motor score. Results When accounting for all four variables, only ADR was significantly associated with bowel independence (OR = 0.970, 95% CI: 0.942–0.997, P = 0.030), and both ADR and IMLL were strongly associated with bladder independence (OR = 0.967, 95% CI: 0.936–0.999, P = 0.046 and OR = 0.948, 95% CI: 0.919–0.978, P = 0.0007, respectively). 32% of the variation in overall independence scores were explained by all four predictive variables, but only ADR was significantly associated with overall independence after accounting for all other predictive variables (β = −0.469, 95% CI: −0.719, −0.218, P = 0.0004). Conclusions Our results suggest that the MRI-measured extent of spinal cord lesion may be predictive of bowel, bladder, and overall independence following cervical SCI.

Significance of physical factors on activities of daily living in patients with tetraplegia after spinal cord injury: a retrospective study

BackgroundTetraplegia is a debilitating sequela of spinal cord injury (SCI). However, comprehensive approaches for determining the influence of various factors on activities of daily living (ADL) in patients with tetraplegia are limited. Therefore, this study aimed to determine the influence of physical factors on ADL in patients with tetraplegia after adjusting for demographic, SCI-related, and cognitive factors.MethodsThis retrospective cross-sectional study enrolled 201 patients with tetraplegia who underwent inpatient rehabilitation at the National Rehabilitation Center in South Korea between 2019 and 2021. Patients’ mean age was 50.5 years (standard deviation, 16.3), and 170 (84.6%) were men. The Korean Spinal Cord Independence Measure III (K-SCIM III) was used as the main outcome measure to assess patients’ ADL ability. Hierarchical multiple regression modeling was conducted with K-SCIM as the dependent variable to examine the level of functioning and relative influencing factors.ResultsUpper-extremity motor score (UEMS), upper-extremity spasticity and sitting balance scores were significant predictors of self-care; lower-extremity motor score (LEMS), musculoskeletal pain of shoulder, and sitting balance were significant predictors of respiratory and sphincter management; UEMS, LEMS, and sitting balance score were significant predictors of mobility; and UEMS, LEMS, musculoskeletal pain of shoulder, and sitting balance scores were significant predictors of the K-SCIM III total score after adjustment for demographic, SCI-related, and cognitive factors.ConclusionsPhysical factors had the greatest impact on all subscores and the K-SCIM III total score. Upper- and lower-extremity muscle strength and sitting balance significantly affected functional ability across all subscores.

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

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

Dynamic properties in functional connectivity changes and striatal dopamine deficiency in Parkinson's disease.

Recent studies in Parkinson's disease (PD) patients reported disruptions in dynamic functional connectivity (dFC, i.e., a characterization of spontaneous fluctuations in functional connectivity over time). Here, we assessed whether the integrity of striatal dopamine terminals directly modulates dFC metrics in two separate PD cohorts, indexing dopamine-related changes in large-scale brain network dynamics and its implications in clinical features. We pooled data from two disease-control cohorts reflecting early PD. From the Parkinson's Progression Marker Initiative (PPMI) cohort, resting-state functional magnetic resonance imaging (rsfMRI) and dopamine transporter (DaT) single-photon emission computed tomography (SPECT) were available for 63 PD patients and 16 age- and sex-matched healthy controls. From the clinical research group 219 (KFO) cohort, rsfMRI imaging was available for 52 PD patients and 17 age- and sex-matched healthy controls. A subset of 41 PD patients and 13 healthy control subjects additionally underwent 18F-DOPA-positron emission tomography (PET) imaging. The striatal synthesis capacity of 18F-DOPA PET and dopamine terminal quantity of DaT SPECT images were extracted for the putamen and the caudate. After rsfMRI pre-processing, an independent component analysis was performed on both cohorts simultaneously. Based on the derived components, an individual sliding window approach (44 s window) and a subsequent k-means clustering were conducted separately for each cohort to derive dFC states (reemerging intra- and interindividual connectivity patterns). From these states, we derived temporal metrics, such as average dwell time per state, state attendance, and number of transitions and compared them between groups and cohorts. Further, we correlated these with the respective measures for local dopaminergic impairment and clinical severity. The cohorts did not differ regarding age and sex. Between cohorts, PD groups differed regarding disease duration, education, cognitive scores and L-dopa equivalent daily dose. In both cohorts, the dFC analysis resulted in three distinct states, varying in connectivity patterns and strength. In the PPMI cohort, PD patients showed a lower state attendance for the globally integrated (GI) state and a lower number of transitions than controls. Significantly, worse motor scores (Unified Parkinson's Disease Rating Scale Part III) and dopaminergic impairment in the putamen and the caudate were associated with low average dwell time in the GI state and a low total number of transitions. These results were not observed in the KFO cohort: No group differences in dFC measures or associations between dFC variables and dopamine synthesis capacity were observed. Notably, worse motor performance was associated with a low number of bidirectional transitions between the GI and the lesser connected (LC) state across the PD groups of both cohorts. Hence, in early PD, relative preservation of motor performance may be linked to a more dynamic engagement of an interconnected brain state. Specifically, those large-scale network dynamics seem to relate to striatal dopamine availability. Notably, most of these results were obtained only for one cohort, suggesting that dFC is impacted by certain cohort features like educational level, or disease severity. As we could not pinpoint these features with the data at hand, we suspect that other, in our case untracked, demographical features drive connectivity dynamics in PD. PRACTITIONER POINTS: Exploring dopamine's role in brain network dynamics in two Parkinson's disease (PD) cohorts, we unraveled PD-specific changes in dynamic functional connectivity. Results in the Parkinson's Progression Marker Initiative (PPMI) and the KFO cohort suggest motor performance may be linked to a more dynamic engagement and disengagement of an interconnected brain state. Results only in the PPMI cohort suggest striatal dopamine availability influences large-scale network dynamics that are relevant in motor control.

Spontaneous cortical activity is altered in persons with HIV and related to domain-specific cognitive function.

Whilst the average lifespan of persons with HIV now approximates that of the general population, these individuals are at a much higher risk of developing cognitive impairment with ∼35-70% experiencing at least subtle cognitive deficits. Previous works suggest that HIV impacts both low-level primary sensory regions and higher-level association cortices. Notably, multiple neuroHIV studies have reported elevated levels of spontaneous cortical activity during the pre-stimulus baseline period of task-based experiments, but only a few have examined such activity during resting-state conditions. In the current study, we examined such spontaneous cortical activity using magnetoencephalography in 79 persons with HIV and 83 demographically matched seronegative controls and related this neural activity to performance on neuropsychological assessments of cognitive function. Consistent with previous works, persons with HIV exhibited stronger spontaneous gamma activity, particularly in inferior parietal, prefrontal and superior temporal cortices. In addition, serostatus moderated the relationship between spontaneous beta activity and attention, motor and processing speed scores, with controls but not persons with HIV showing stronger beta activity with better performance. The current results suggest that HIV predominantly impacts spontaneous activity in association cortices, consistent with alterations in higher-order brain function, and may be attributable to deficient GABAergic signalling, given its known role in the generation of gamma and beta oscillations. Overall, these effects align with previous studies showing aberrant spontaneous activity in persons with HIV and provide a critical new linkage to domain-specific cognitive dysfunction.

Association of germinal matrix hemorrhage volume with neurodevelopment and hydrocephalus.

The objective of this study was to evaluate whether volumetric measurements on early cranial ultrasound (CUS) in high-grade germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) are associated with hydrocephalus and neurodevelopmental metrics. A retrospective case series analysis of infants with high-grade GMH-IVH admitted to the St. Louis Children's Hospital neonatal intensive care unit between 2007 and 2015 who underwent neurodevelopmental testing using the Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) at 2 years of corrected age was performed. GMH volume, periventricular hemorrhagic infarction volume, and frontotemporal horn ratio were obtained from direct review of neonatal CUS studies. Univariate and multivariable regression models were used to evaluate the association between hemorrhage volumes and hydrocephalus requiring permanent CSF diversion with ventricular shunt or endoscopic third ventriculostomy with or without choroid plexus cauterization and composite Bayley-III cognitive, language, and motor scores. Forty-three infants (29 males, mean gestational age 25 weeks) met the inclusion criteria. The mean age at time of the CUS with the largest hemorrhage volume or first diagnosis of highest grade was 6.2 days. Nineteen patients underwent treatment for hydrocephalus with permanent CSF diversion. In multivariable analyses, larger GMH volume was associated with worse estimated Bayley-III cognitive (left-sided GMH volume: p = 0.048, total GMH volume: p = 0.023) and motor (left-sided GMH volume: p = 0.010; total GMH volume: p = 0.014) scores. Larger periventricular hemorrhagic infarction volume was associated with worse estimated Bayley-III motor scores (each side p < 0.04). Larger left-sided (OR 2.55, 95% CI 1.10-5.88; p = 0.028) and total (OR 1.35, 95% CI 1.01-1.79; p = 0.041) GMH volumes correlated with hydrocephalus. There was no relationship between early ventricular volume and hydrocephalus or neurodevelopmental outcomes. Location-specific hemorrhage volume on early CUS may be prognostic for neurodevelopmental and hydrocephalus outcomes in high-grade GMH-IVH.

Decompressive craniectomy in children: indications and outcome from a tertiary centre.

The role of decompressive craniectomy (DC) is as a rescue therapy for the treatment of intracranial hypertension. The indications for the DC are variable. The clinical details, imaging, operative findings and follow-up data of children less than or equal to 18years of age were reviewed for more information on the children who underwent DC in the last 5years. During the study period, a total of 128 children underwent DC. The trauma cases were 66, and the non-trauma cases were 62. The common indication for DC was pure acute subdural hematoma 33 (50%), followed by contusion 10 (15%) in the trauma group, and in non-trauma, arterial infarction in 20 (32%) and cerebral venous thrombosis in 17 (27%). Hemicraniectomy was done in 114 (89%), and bifrontal craniectomy was done in 7 (5.4%) cases. The median duration follow-up was 7months in non-trauma and 6months in trauma. GCS was less than 8, the motor score was less than 3, and pupillary asymmetry, hypotension and basal cistern effacement were factors related to an unfavourable outcome in the non-trauma group. In regression analysis, only a motor score of less than three was associated with the non-trauma group. Age less than 10years, GCS less than 8, motor score less than three and preoperative infarction were the predictive factors in univariate analysis, and only GCS less than 8 was the predictive factor for unfavourable factors in regression analysis in the trauma group. The DC is performed as a lifesaving procedure. The unfavourable outcome is slightly higher in non-trauma cases compared to trauma cases. However, the mortality rate is high in trauma cases.

Preeclampsia, Fetal Growth Restriction, and 24-Month Neurodevelopment in Very Preterm Infants

Preeclampsia has direct influences on a developing fetus and may impact postnatal health, and fetal growth restriction (FGR) is often seen co-occurring with preeclampsia. The development of children born very preterm after preeclampsia diagnosis with and without FGR is not well characterized. To examine the associations of preeclampsia and FGR with developmental and/or behavioral outcomes in a cohort of very preterm infants. In this cohort study, infants in the prospective Neonatal Neurobehavior and Outcomes in Very Preterm Infants study were enrolled between April 2014 and June 2016 from 9 US university-affiliated neonatal intensive care units (NICUs). Eligible infants were born before 30 weeks' gestation. Infants were excluded for any major congenital anomalies and for maternal age younger than 18 years or cognitive impairment impacting the ability to provide informed consent. Data analysis was performed from November 2023 to January 2024. Maternal preeclampsia and FGR in very preterm infants. The Bayley-III cognition, motor, and language scores less than 85 (-1 SD) indicated developmental delay. Child Behavior Checklist/Preschool 1.5-5 T-scores greater than or equal to 64 for internalizing, externalizing, or total problems indicated clinical importance. Of 704 infants enrolled, 529 (mean [SD] gestational age, 27.0 [1.9] weeks; 287 male [54.3%]) were studied at 24-month follow-up. A total of 94 infants' mothers had preeclampsia (23.2%), and 46 infants (8.7%) had FGR. In adjusted models, preeclampsia was not associated with Bayley-III (cognitive, B = 3.43 [95% CI, -0.19 to 6.66]; language, B = 3.92 [95% CI, 0.44 to 7.39]; motor, B = 1.86 [95% CI, -1.74 to 5.47]) or Child Behavior Checklist/Preschool 1.5-5 (internalizing, B = -0.08 [95% CI, -2.58 to 2.73]; externalizing, B = 0.69 [95% CI, -1.76 to 3.15]; total, B = 0.21 [95% CI, -2.48 to 2.91]) outcomes. FGR was associated with significantly lower Bayley-III scores (cognitive, B = -8.61 [95% CI, -13.33 to -3.89]; language, B = -8.29 [95% CI, -12.95 to -3.63]; motor, B = -7.60 [95% CI, -12.40 to -2.66]), regardless of preeclampsia status. In this cohort study of preterm infants, preeclampsia was not associated with developmental and/or behavioral outcomes, but infants with FGR may be prone to developmental delays. These findings suggest future areas of research for understanding the roles of preeclampsia and FGR separately and together in early child development for preterm infants.

Health-related quality of life after anterior-only fixation of lower cervical spine fractures: long-term follow-up

Background The management of lower cervical spine fractures at the cervicothoracic junction is challenging and the selection of suitable approach is a matter of debate. The results of anterior fixation of those injuries in the available literatures are ambiguous due to the heterogeneity of the studied groups and lacking long-term follow-up. Moreover, the assessment of patients’ quality of life was not taken into consideration. Our aim was to assess the health-related quality of life and long-term follow-up of a homogenous group of patients of unstable lower cervical spine fractures managed by anterior-only fixation and iliac autograft. Patients and methods Data from hospital records of 13 cases of lower cervical spine fracture managed by anterior fixation and graft were examined and analyzed. All cases were operated as the Subaxial Injury Classification (SLIC) score was greater than or equal to 5. The International Standards for Neurological Classification of Spinal Cord Injury and American Spinal Injury Association (ASIA) scores were used to assess patients’ neurologic status; segmental kyphosis angle for cervical kyphosis and short-Form 36-item was used for health-related quality of life assessment. Results Thirteen cases were included in this series with a mean age of 36.15 ± 7.82 years. C6 was fractured in 3 cases (24%), C7 in 5 cases (38%) and both C6 and C7 in 5 cases (38%). All cases have a SLIC score more than 5 with a mean of 7.0 ± 1.53 (range 5:9). The mean follow-up was 75.54 ± 22.33 months. The operative time was 90.62 ± 20.67 min The total motor score was improved from 72 ± 33.44 preoperatively to 76.92 ± 31.80 at the final follow-up. The segmental kyphosis angle was improved from 15.62 ± 3.25° preoperatively to −9.84 ± 1.77° directly postoperative and −1.30 ± 2.32° at the final follow-up and the short-Form 36-item total score was 75.04 ± 24.26. Conclusion The procedure proved to be safe and has yielded excellent results. The late patient outcome from the quality-of-life perspectives was not affected by loss of cervical lordosis, but on the contrary improved significantly in correlation with improvement of patients’ motor power.

Development of an animal model of hypothyroxinemia during pregnancy in Wistar rats

AbstractBackgroundHypothyroxinemia is a subclinical thyroid hormone deficiency in which the mother has inadequate levels of T4 during pregnancy. The fetus relies entirely on the mother's T4 hormone level for early neurodevelopment. Isolated maternal hypothyroxinemia (IMH) in the first trimester of pregnancy can lead to lower intelligence, lower motor scores, and a higher risk of mental illness in descendants. Here, we focus on the autism‐like behavior of IMH offspring.MethodsThe animals were administered 1 ppm of propylthiouracil (PTU) for 9 weeks. Then, the concentrations of T3, T4, and thyroid‐stimulating hormone (TSH) were detected using enzyme‐linked immunosorbent assay (ELISA) to verify the developed animal model of IMH. We performed four behavioral experiments, including the marble burying test, open‐field test, three‐chamber sociability test, and Morris water maze, to explore the autistic‐like behavior of 40‐day‐old offspring rats.ResultsThe ELISA test showed that the serum T3 and TSH concentrations in the model group were normal compared with the negative control group, whereas the T4 concentration decreased. In the behavioral experiments, the number of hidden marbles in the offspring of IMH increased significantly, the frequency of entering the central compartment decreased, and the social ratio decreased significantly.ConclusionThe animal model of IMH was developed by the administration of 1 ppm of PTU for 9 weeks, and there were autistic‐like behavior changes such as anxiety, weakened social ability, and repeated stereotyping in the IMH offspring by 40 days.

Effect of Intermittent Theta Burst Stimulation Dual-Target Stimulation on Lower Limb Function in Patients with Incomplete Spinal Cord Injury: A Randomized, Single-Blind, Sham-Controlled Study

To explore the influence of intermittent theta burst stimulation (iTBS) dual-target stimulation on lower limb function in patients with incomplete spinal cord injury (iSCI). A randomized, single -blind, sham-controlled trial was used in this study. Thirty iSCI patients with lower limb dysfunction meeting the inclusion criteria were randomly divided into a sham group and an iTBS group, with 15 cases in each group. The iTBS group received conventional rehabilitation therapy combined with iTBS dual-target stimulation on the central cerebral sulcus and the nerve root of the spinal cord injury segment. The sham group was treated with conventional rehabilitation therapy combined with iTBS dual-target sham stimulation therapy. Comprehensive functional assessment was performed on all patients before treatment, on the day 3 and day 21 of treatment. The main evaluation indicators were as follows: amplitude and latency of motor-evoked potential (MEP) in the anterior tibial muscles of both lower limbs, latency of sensory-evoked potential (SEP) of both lower limbs, knee flexor strength and knee extensor strength, lower extremity motor score (LEMS), lower extremity sensory score, spinal cord independence measure (SCIM) score, and gait parameters (stride speed, stride frequency, stride length, and ground reaction force). On day 21 of treatment, in the iTBS group, the MEP amplitude of the anterior tibial muscles increased, the latency of MEP shortened, knee flexor strength and knee extensor strength increased, and the LEMS and SCIM score of both lower limbs increased. In addition, there were statistically significant differences in the muscle strength of the knee flexion muscle, knee extensor muscle, MEP amplitude, LEMS, and SCIM between the 2 groups (P < 0.05). Among the 10 patients who could walk with an assisted walker, the step length and step frequency of the iTBS group were increased compared with the sham group after treatment (P < 0.01), and the ground reaction force was increased (P < 0.05). There was no significant difference in the lower extremity sensory score of the lower limbs between the 2 groups (P>0.05). ITBS dual-target stimulation can significantly improve the motor function of both lower limbs in patients with iSCI but does not significantly improve the sensory function of both lower limbs. Therefore, this treatment mode may participate in the reconstruction and repair of some nerve circuits in patients with iSCI. In addition, iTBS dual-target stimulation can improve the ability of iSCI patients to perform daily living.

Lumbar Disc Herniation—the Significance of Symptom Duration for the Indication for Surgery.

Lumbar disc surgery is among the more common spinal procedures. In this paper, we report the current treatment recommendations for patients with symptomatic disc herniation. This review is based on pertinent publications retrieved by a selective literature search in PubMed using the terms [timing] AND [lumbar disc herniation], supplemented by other relevant articles and guidelines. Symptoms resolve in 60% to 80% of patients with herniated discs in 6-12 weeks, and in 80% to 90% over the long term (≥ 1 year). According to the guidelines, 6-12 weeks of conservative treatment are recommended in the absence of significant neu - rologic deficits. Early surgery is indicated in case of worsening pain or new onset of neurologic deficits. Lumbar disc herniation associated bladder or bowel dysfunction (cauda equina syndrome) is considered an absolute surgical emergency that requires immediate decompression (within 24 to 48 hours). Patients with severe motor deficits (MRC ≤ 3/5) benefit from early intervention and should be offered surgery within three days, if possible, for the best chance of recovery. The degree of weakness and the duration of symptoms have been identified as risk factors for incomplete recovery. Early surgery can be considered in patients with mild paresis (MRC 4/5) in case of functional impairment (e.g., quadriceps paresis). Longer symptom duration and lower motor scores are associated with worse outcome and a lower chance of neurologic recovery. The recovery rate for motor deficits ranges from 33% to 75%, depending on the timing and modality of treatment as well as the motor score.

Prognostic value of tissue bridges in cervical spinal cord injury: a longitudinal, multicentre, retrospective cohort study

The accuracy of prognostication in patients with cervical spinal cord injury (SCI) needs to be improved. We aimed to explore the prognostic value of preserved spinal tissue bridges-injury-spared neural tissue adjacent to the lesion-for prediction of sensorimotor recovery in a large, multicentre cohort of people with SCI. For this longitudinal study, we included patients with acute cervical SCI (vertebrae C1-C7) admitted to one of three trauma or rehabilitation centres: Murnau, Germany (March 18, 2010-March 1, 2021); Zurich, Switzerland (May 12, 2002-March 2, 2019); and Denver, CO, USA (Jan 12, 2010-Feb 16, 2017). Patients were clinically assessed at admission (baseline), at discharge (3 months), and at 12 months post SCI. Midsagittal tissue bridges were quantified from T2-weighted images assessed at 3-4 weeks post SCI. Fractional regression and unbiased recursive partitioning models, adjusted for age, sex, centre, and neurological level of injury, were used to assess associations between tissue bridge width and baseline-adjusted total motor score, pinprick score, and light touch scores at 3 months and 12 months. Patients were stratified into subgroups according to whether they showed better or worse predicted recovery. The cohort included 227 patients: 93 patients from Murnau (22 [24%] female); 43 patients from Zurich (four [9%] female); and 91 patients from Denver (14 [15%] female). 136 of these participants (from Murnau and Zurich) were followed up for up to 12 months. At 3 months, per preserved 1 mm of tissue bridge at baseline, patients recovered a mean of 9·3% (SD 0·9) of maximal total motor score (95% CI 7·5-11.2), 8·6% (0·8) of maximal pinprick score (7·0-10·1), and 10·9% (0·8) of maximal light touch score (9·4-12·5). At 12 months post SCI, per preserved 1 mm of tissue bridge at baseline, patients recovered a mean of 10·9% (1·3) of maximal total motor score (8·4-13·4), 5·7% (1·3) of maximal pinprick score (3·3-8·2), and 6·9% (1·4) of maximal light touch score (4·1-9·7). Partitioning models identified a tissue bridge cutoff width of 2·0 mm to be indicative of higher or lower 3-month total motor, pinprick, and light touch scores, and a cutoff of 4·0 mm to be indicative of higher and lower 12-month scores. Compared with models that contained clinical predictors only, models additionally including tissue bridges had significantly improved prediction accuracy across all three centres. Tissue bridges, measured in the first few weeks after SCI, are associated with short-term and long-term clinical improvement. Thus, tissue bridges could potentially be used to guide rehabilitation decision making and to stratify patients into more homogeneous subgroups of recovery in regenerative and neuroprotective clinical trials. Wings for Life, International Foundation for Research in Paraplegia, EU project Horizon 2020 (NISCI grant), and ERA-NET NEURON.

Safety and efficiency of Wharton’s Jelly-derived mesenchymal stem cell administration in patients with traumatic brain injury: First results of a phase I study

BACKGROUND Traumatic brain injury (TBI) is characterized by a disruption in the normal function of the brain due to an injury following a trauma, which can potentially cause severe physical, cognitive, and emotional impairment. Stem cell transplantation has evolved as a novel treatment modality in the management of TBI, as it has the potential to arrest the degeneration and promote regeneration of new cells in the brain. Wharton’s Jelly-derived mesenchymal stem cells (WJ-MSCs) have recently shown beneficial effects in the functional recovery of neurological deficits. AIM To evaluate the safety and efficiency of MSC therapy in TBI. METHODS We present 6 patients, 4 male and 2 female aged between 21 and 27 years who suffered a TBI. These 6 patients underwent 6 doses of intrathecal, intramuscular (i.m.) and intravenous transplantation of WJ-MSCs at a target dose of 1 × 106/kg for each application route. Spasticity was assessed using the Modified Ashworth scale (MAS), motor function according to the Medical Research Council Muscle Strength Scale, quality of life was assessed by the Functional Independence Measure (FIM) scale and Karnofsky Performance Status scale. RESULTS Our patients showed only early, transient complications, such as subfebrile fever, mild headache, and muscle pain due to i.m. injection, which resolved within 24 h. During the one year follow-up, no other safety issues or adverse events were reported. These 6 patients showed improvements in their cognitive abilities, muscle spasticity, muscle strength, performance scores and fine motor skills when compared before and after the intervention. MAS values, which we used to assess spasticity, were observed to statistically significantly decrease for both left and right sides (P &lt; 0.001). The FIM scale includes both motor scores (P &lt; 0.05) and cognitive scores (P &lt; 0.001) and showed a significant increase in pretest posttest analyses. The difference observed in the participants’ Karnofsky Performance Scale values pre and post the intervention was statistically significant (P &lt; 0.001). CONCLUSION This study showed that cell transplantation has a safe, effective and promising future in the management of TBI.

Transcutaneous Electrical Spinal Cord Stimulation Increased Target-Specific Muscle Strength and Locomotion in Chronic Spinal Cord Injury.

The recovery of locomotion is greatly prioritized, and neuromodulation has been emerging as a promising approach in recent times. Single-subject research design. A laboratory at The Hong Kong Polytechnic University. To investigate the effects of augmenting activity-based therapy (ABT) to transcutaneous electrical spinal cord stimulation (TSCS) on enhancing specific lower limb muscle strength and improving locomotor ability in an individual with chronic incomplete spinal cord injury (iSCI). An individual with iSCI underwent two phases of treatment, ABT alone followed by combined ABT+TSCS, each for a period of 10 weeks. The TSCS stimulated T10-T11 and T12-L1 segments with a frequency of 30 Hz at an intensity between 105 mA and 130 mA. Manual muscle testing, 6 min walk test (6MWT), and surface electromyography (EMG) responses of specific lower limb muscles were measured. Additionally, spasticity and sensorimotor examinations were conducted every two weeks, while pain tolerance was recorded after each treatment session. After the ABT+TSCS treatment, there was an increase in overall muscle strength grading (from 1.8 ± 0.3 to 2.2 ± 0.6 out of 5.0). The 6MWT showed a greater increase in walking distance (3.5 m to 10 m) after combined treatment than ABT alone. In addition, the EMG response of the anterior rectus femoris, biceps femoris, medial gastrocnemius, and tibialis anterior after ABT+TSCS increased more than after ABT alone. The spasticity grade was reduced (from 0.8 ± 0.7 to 0.5 ± 0.6) whereas the average lower limb motor score increased from 17 to 23 points. No adverse effects were reported. ABT+TSCS increased the target-specific lower limb muscle strength and walking ability more than ABT alone in an individual with chronic iSCI.

Prediction of motor and non-motor Parkinson’s disease symptoms using serum lipidomics and machine learning: a 2-year study

Identifying biological factors which contribute to the clinical progression of heterogeneous motor and non-motor phenotypes in Parkinson’s disease may help to better understand the disease process. Several lipid-related genetic risk factors for Parkinson’s disease have been identified, and the serum lipid signature of Parkinson’s disease patients is significantly distinguishable from controls. However, the extent to which lipid profiles are associated with clinical outcomes remains unclear. Untargeted high-performance liquid chromatography-tandem mass spectrometry identified >900 serum lipids in Parkinson’s disease subjects at baseline (n = 122), and the potential for machine learning models using these lipids to predict motor and non-motor clinical scores after 2 years (n = 67) was assessed. Machine learning models performed best when baseline serum lipids were used to predict the 2-year future Unified Parkinson’s disease rating scale part three (UPDRS III) and Geriatric Depression Scale scores (both normalised root mean square error = 0.7). Feature analysis of machine learning models indicated that species of lysophosphatidylethanolamine, phosphatidylcholine, platelet-activating factor, sphingomyelin, diacylglycerol and triacylglycerol were top predictors of both motor and non-motor scores. Serum lipids were overall more important predictors of clinical outcomes than subject sex, age and mutation status of the Parkinson’s disease risk gene LRRK2. Furthermore, lipids were found to better predict clinical scales than a panel of 27 serum cytokines previously measured in this cohort (The Michael J. Fox Foundation LRRK2 Clinical Cohort Consortium). These results suggest that lipid changes may be associated with clinical phenotypes in Parkinson’s disease.

Factors associated with self-awareness impairment in an inpatient brain injury rehabilitation cohort

ABSTRACT Background Self-awareness impairment is common following acquired brain injury and can impact rehabilitation outcomes. Knowledge of factors associated with impaired self-awareness may assist with rehabilitation planning. Objectives To identify factors associated with self-awareness and determine predictors of self-awareness impairment for adults with traumatic brain injury (TBI) and stroke. Design and methods A retrospective cohort study of rehabilitation inpatients was conducted by medical record audit. Self-awareness was measured using the Self-awareness of Deficits Interview (SADI). Relationships between SADI scores and demographic and clinical variables were identified with non-parametric statistics. Predictors of SADI scores were identified using ordinal regression analyses for TBI and stroke groups. Results Participants were 149 adults (18–70 years) with TBI (n = 110) and stroke (n = 39). For TBI, longer post-traumatic amnesia (PTA), lower functional cognition/communication, and behaviors of concern (BoC) were significantly associated with higher SADI scores (i.e. impaired self-awareness). For stroke, lower functional cognition/communication and motor scores were associated with higher SADI scores. Impaired self-awareness was predicted by PTA duration, acute length of stay and presence of BoC for the TBI group, and by functional cognition/communication for the stroke group. Conclusion Different factors were associated with impaired self-awareness for individuals with TBI and stroke during inpatient rehabilitation.

Correlation of bilateral M1 hand area excitability and overall functional recovery after spinal cord injury: protocol for a prospective cohort study

BackgroundAfter spinal cord injury (SCI), a large number of survivors suffer from severe motor dysfunction (MD). Although the injury site is in the spinal cord, excitability significantly decreases in the primary motor cortex (M1), especially in the lower extremity (LE) area. Unfortunately, M1 LE area-targeted repetitive transcranial magnetic stimulation (rTMS) has not achieved significant motor improvement in individuals with SCI. A recent study reported that the M1 hand area in individuals with SCl contains a compositional code (the movement-coding component of neural activity) that links matching movements from the upper extremities (UE) and the LE. However, the correlation between bilateral M1 hand area excitability and overall functional recovery is unknown.ObjectiveTo clarify the changes in the excitability of the bilateral M1 hand area after SCI and its correlation with motor recovery, we aim to specify the therapeutic parameters of rTMS for SCI motor rehabilitation.MethodsThis study is a 12-month prospective cohort study. The neurophysiological and overall functional status of the participants will be assessed. The primary outcomes included single-pulse and paired-pulse TMS. The second outcome included functional near-infrared spectroscopy (fNIRS) measurements. Overall functional status included total motor score, modified Ashworth scale score, ASIA Impairment Scale grade, spinal cord independence measure and modified Barthel index. The data will be recorded for individuals with SCI at disease durations of 1 month, 2 months, 4 months, 6 months and 12 months. The matched healthy controls will be measured during the same period of time after recruitment.DiscussionThe present study is the first to analyze the role of bilateral M1 hand area excitability changes in the evaluation and prediction of overall functional recovery (including motor function and activities of daily living) after SCI, which will further expand the traditional theory of the predominant role of M1, optimize the current rTMS treatment, and explore the brain-computer interface design for individuals with SCI.Trial registration numberChiCTR2300068831.

Riluzole for Degenerative Cervical Myelopathy

The modified Japanese Orthopaedic Association (mJOA) scale is the most common scale used to represent outcomes of degenerative cervical myelopathy (DCM); however, it lacks consideration for neck pain scores and neglects the multidimensional aspect of recovery after surgery. To use a global statistical approach that incorporates assessments of multiple outcomes to reassess the efficacy of riluzole in patients undergoing spinal surgery for DCM. This was a secondary analysis of prespecified secondary end points within the Efficacy of Riluzole in Surgical Treatment for Cervical Spondylotic Myelopathy (CSM-PROTECT) trial, a multicenter, double-blind, phase 3 randomized clinical trial conducted from January 2012 to May 2017. Adult surgical patients with DCM with moderate to severe myelopathy (mJOA scale score of 8-14) were randomized to receive either riluzole or placebo. The present study was conducted from July to December 2023. Riluzole (50 mg twice daily) or placebo for a total of 6 weeks, including 2 weeks prior to surgery and 4 weeks following surgery. The primary outcome measure was a difference in clinical improvement from baseline to 1-year follow-up, assessed using a global statistical test (GST). The 36-Item Short Form Health Survey Physical Component Score (SF-36 PCS), arm and neck pain numeric rating scale (NRS) scores, American Spinal Injury Association (ASIA) motor score, and Nurick grade were combined into a single summary statistic known as the global treatment effect (GTE). Overall, 290 patients (riluzole group, 141; placebo group, 149; mean [SD] age, 59 [10.1] years; 161 [56%] male) were included. Riluzole showed a significantly higher probability of global improvement compared with placebo at 1-year follow-up (GTE, 0.08; 95% CI, 0.00-0.16; P = .02). A similar favorable global response was seen at 35 days and 6 months (GTE for both, 0.07; 95% CI, -0.01 to 0.15; P = .04), although the results were not statistically significant. Riluzole-treated patients had at least a 54% likelihood of achieving better outcomes at 1 year compared with the placebo group. The ASIA motor score and neck and arm pain NRS combination at 1 year provided the best-fit parsimonious model for detecting a benefit of riluzole (GTE, 0.11; 95% CI, 0.02-0.16; P = .007). In this secondary analysis of the CSM-PROTECT trial using a global outcome technique, riluzole was associated with improved clinical outcomes in patients with DCM. The GST offered probability-based results capable of representing diverse outcome scales and should be considered in future studies assessing spine surgery outcomes.

Improvement in functional motor scores in patients with non-ambulatory spinal muscle atrophy during Nusinersen treatment in South Korea: a single center study

We analyzed the changes in various motor function scores over a four-year period in patients with non-ambulatory spinal muscular atrophy (SMA) during Nusinersen treatment. Patients underwent Hammersmith Infant Neurological Examination (HINE) or Hammersmith Functional Motor Scale Expanded (HFMSE) before treatment, and approximately every 4 months thereafter. Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) or Children’s Hospital of Philadelphia – Adult Test of Neuromuscular Disorders (CHOP ATEND), Revised Upper Limb Module (RULM), and Motor Function Measure (MFM) were performed based on baseline functional status. Narrative interviews were conducted to explore post-treatment physical improvement regarding activities of daily living (ADLs) and fatigue after ADLs. Based on HFMSE results, 9 patients achieved minimum clinically important differences. Average rates of change (slopes) with corresponding 95% confidence intervals for all assessment tools were in a positive direction. CHOP-INTEND showed the most prominent improvement in children and adolescents followed by HFMSE. Improvements in CHOP-ATEND were most noticeable in adults. Improvements were accompanied by changes in ADLs as observed in the narrative interviews. It is necessary to consider various functional aspects to determine the effectiveness of Nusinersen therapy. The objective assessment of the therapeutic effect of Nusinersen in non-ambulatory SMA requires consideration of functional aspects and the related ADLs.