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"Paralysis"
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The properties of water
When her older sister Marni is paralyzed jumping off the cliffs into the lake near their house, twelve-year-old Lace feels responsible for the accident and struggles to find a way to help heal her family.
Book
Lizzie!
A bright, curious girl in a wheelchair who enjoys visiting a petting zoo in her Florida town uncovers a mystery surrounding a shack full of screeching monkeys.
Book
Single-cell and spatial atlases of spinal cord injury in the Tabulae Paralytica
Here, we introduce the
Tabulae Paralytica
—a compilation of four atlases of spinal cord injury (SCI) comprising a single-nucleus transcriptome atlas of half a million cells, a multiome atlas pairing transcriptomic and epigenomic measurements within the same nuclei, and two spatial transcriptomic atlases of the injured spinal cord spanning four spatial and temporal dimensions. We integrated these atlases into a common framework to dissect the molecular logic that governs the responses to injury within the spinal cord
1
. The
Tabulae Paralytica
uncovered new biological principles that dictate the consequences of SCI, including conserved and divergent neuronal responses to injury; the priming of specific neuronal subpopulations to upregulate circuit-reorganizing programs after injury; an inverse relationship between neuronal stress responses and the activation of circuit reorganization programs; the necessity of re-establishing a tripartite neuroprotective barrier between immune-privileged and extra-neural environments after SCI and a failure to form this barrier in old mice. We leveraged the
Tabulae Paralytica
to develop a rejuvenative gene therapy that re-established this tripartite barrier, and restored the natural recovery of walking after paralysis in old mice. The
Tabulae Paralytica
provides a window into the pathobiology of SCI, while establishing a framework for integrating multimodal, genome-scale measurements in four dimensions to study biology and medicine.
The
Tabulae Paralytica
, a compilation of four molecular atlases of spinal cord injury, provides a window into the pathobiology of spinal cord injury, establishing a framework for integrating multimodal, genome-scale measurements in four dimensions to study biology and medicine.
Journal Article
The neurons that restore walking after paralysis
A spinal cord injury interrupts pathways from the brain and brainstem that project to the lumbar spinal cord, leading to paralysis. Here we show that spatiotemporal epidural electrical stimulation (EES) of the lumbar spinal cord
1
–
3
applied during neurorehabilitation
4
,
5
(EES
REHAB
) restored walking in nine individuals with chronic spinal cord injury. This recovery involved a reduction in neuronal activity in the lumbar spinal cord of humans during walking. We hypothesized that this unexpected reduction reflects activity-dependent selection of specific neuronal subpopulations that become essential for a patient to walk after spinal cord injury. To identify these putative neurons, we modelled the technological and therapeutic features underlying EES
REHAB
in mice. We applied single-nucleus RNA sequencing
6
–
9
and spatial transcriptomics
10
,
11
to the spinal cords of these mice to chart a spatially resolved molecular atlas of recovery from paralysis. We then employed cell type
12
,
13
and spatial prioritization to identify the neurons involved in the recovery of walking. A single population of excitatory interneurons nested within intermediate laminae emerged. Although these neurons are not required for walking before spinal cord injury, we demonstrate that they are essential for the recovery of walking with EES following spinal cord injury. Augmenting the activity of these neurons phenocopied the recovery of walking enabled by EES
REHAB
, whereas ablating them prevented the recovery of walking that occurs spontaneously after moderate spinal cord injury. We thus identified a recovery-organizing neuronal subpopulation that is necessary and sufficient to regain walking after paralysis. Moreover, our methodology establishes a framework for using molecular cartography to identify the neurons that produce complex behaviours.
Transcriptomic analysis following epidural electrical stimulation of the lumbar spinal cord during neurorehabilitation in mice identifies a population of neurons that orchestrates the restoration of walking following paralysis.
Journal Article
Evaluation of the Efficacy of the Combined Therapy of Botulinum Toxin and Hyaluronic Acid Compared to Conservative Intervention in the Treatment of Chronic Peripheral Facial Paralysis of Oncologic Etiology
Background
Neoplasms in the head and neck often lead to peripheral facial paralysis (PFP), impacting facial expression and causing psychological distress. Standard treatments involve physiotherapy, but botulinum toxin type A (BTA) and hyaluronic acid (HA) injections have shown promise in promoting facial symmetry.
Aim
To assess the effectiveness of combined BTA and HA intervention in PFP patients, comparing it to conventional treatment (physiotherapy).
Method
A single-blind, randomized clinical trial at Hospital de Amor de Barretos included 18 patients, with the control group receiving standard therapy and the combined therapy (CT) group receiving BTA and HA. Evaluations utilized the Sunnybrook facial grading scale (SFGS) and Psychosocial Facial Asymmetry Scale (EPAF) questionnaires, along with photographic analysis.
Results
CT significantly improved facial symmetry and psychosocial aspects compared to the control group. The SFGS scores increased by 27 points in CT versus 3 points in the control group, while EPAF scores decreased by 16 points in CT and increased by 1 point in the control group. Photographic analysis showed improved dynamic smiles in CT patients. Functional gains were more evident at 30 days, with continued improvement over four months. Psychosocial scores increased throughout the study. Only two CT patients reported transient issues with drinking and chewing.
Conclusion
The study suggests the positive impact of combined therapy on psychosocial and functional aspects, emphasizing the need for further robust research to determine its therapeutic potential.
Level of Evidence II
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors
www.springer.com/00266
.
Journal Article
Prediction of early recovery in patients with acute peripheral facial paralysis using serial electroneuronography
This study aimed to determine the preferred timing and measurement sites for electroneuronography (ENoG) to predict early recovery from acute peripheral facial paralysis.
We retrospectively evaluated 42 patients with acute peripheral facial paralysis who received standard treatment with oral corticosteroids. The severity of facial paralysis was assessed at the initial visit and after 1 month using the House-Brackmann grading system. Patients were classified into recovery and non-recovery groups according to changes in the grade. ENoG was performed at the initial visit and after 2 weeks. ENoG amplitudes of four facial muscles (frontalis, nasalis, orbicularis oculi, and orbicularis oris) at the initial visit and after 2 weeks, as well as age, sex, affected side, and diagnosis, were compared between the two groups.
No differences were observed in degeneration ratios across all subsites in the initial ENoG, which can be explained by the fact that Wallerian degeneration is not yet complete at this early stage. However, the second ENoG, performed after degeneration had progressed, showed significant differences across all subsites. Binary logistic regression analysis revealed that the degeneration ratio of the orbicularis oris muscle was the best predictor of early recovery (odds ratio, 0.961; p = 0.014). Receiver operating characteristic curve analysis also revealed that the degeneration ratios of all subsites measured in the second ENoG were useful in predicting early recovery, with the highest possibility at the orbicularis oris muscle (area under the curve = 0.789). When the degeneration ratio exceeded 60% in all subsites in the second ENoG, a favorable prognosis was not expected.
This study provides the preferred testing time and measurement sites for ENoG to predict early recovery from facial paralysis. Given the personal and social impact of facial paralysis, predicting early recovery is crucial for reassuring patients, providing better treatment, and encouraging early reintegration into society.
Journal Article
Noninvasive Reactivation of Motor Descending Control after Paralysis
The present prognosis for the recovery of voluntary control of movement in patients diagnosed as motor complete is generally poor. Herein we introduce a novel and noninvasive stimulation strategy of painless transcutaneous electrical enabling motor control and a pharmacological enabling motor control strategy to neuromodulate the physiological state of the spinal cord. This neuromodulation enabled the spinal locomotor networks of individuals with motor complete paralysis for 2–6 years American Spinal Cord Injury Association Impairment Scale (AIS) to be re-engaged and trained. We showed that locomotor-like stepping could be induced without voluntary effort within a single test session using electrical stimulation and training. We also observed significant facilitation of voluntary influence on the stepping movements in the presence of stimulation over a 4-week period in each subject. Using these strategies we transformed brain–spinal neuronal networks from a dormant to a functional state sufficiently to enable recovery of voluntary movement in five out of five subjects. Pharmacological intervention combined with stimulation and training resulted in further improvement in voluntary motor control of stepping-like movements in all subjects. We also observed on-command selective activation of the gastrocnemius and soleus muscles when attempting to plantarflex. At the end of 18 weeks of weekly interventions the mean changes in the amplitude of voluntarily controlled movement without stimulation was as high as occurred when combined with electrical stimulation. Additionally, spinally evoked motor potentials were readily modulated in the presence of voluntary effort, providing electrophysiological evidence of the re-establishment of functional connectivity among neural networks between the brain and the spinal cord.
Journal Article