Degree Of Paralysis Research Articles

Automatic setting optimization for robotic upper-extremity rehabilitation in patients with stroke using ReoGo-J: a cross-sectional clinical trial

Stroke-induced upper-extremity paralysis affects a substantial portion of the population, necessitating effective rehabilitation strategies. This study aimed to develop an automated program, incorporating the item response theory, for rehabilitation in patients with post-stroke upper-extremity paralysis, focusing on the ReoGo-J device, and to identify suitable robot parameters for robotic rehabilitation. ReoGo-J, a training device for upper-extremity disorders including 71 items, was administered to over 300 patients with varying degrees of post-stroke upper-extremity paralysis. Each item was rated on a three-point scale (0, very difficult; 1, adequate; 2, very easy). The results were analyzed using the graded response model, an extension of the two-parameter logistic model within the framework of the item response theory, to grade the training items based on ability of the patients. The relationship between the predicted ability, an indicator of the predicted ability the paralyzed upper-extremity to perform an item in the item response theory analysis (higher numbers indicate higher ability, lower numbers indicate lower ability), and the items in the Fugl–Meyer assessment (FMA), which indicate the degree of paralysis, was analyzed using Pearson’s correlation coefficient. This study included 312 patients with post-stroke upper-extremity paralysis. The predicted ability (θ) of the tasks included in the original ReoGo-J test for forward reaching, reaching for mouth, rotational reaching, radial reaching (2D), abduction reaching, reaching in eight directions, radial reach (3D), and reaching for head ranged from − 2.0 to − 0.8, − 1.3 to − 0.8, − 1.0 to − 0.1, − 0.7 to 0.3, − 0.2 to 0.4, − 0.4 to 0.6, − 0.1 to 0.6, and 0.5 to 0.6, respectively. Significantly high correlations (r = 0.80) were observed between the predicted ability of all patients and the upper-extremity items of shoulder-elbow-forearm in the FMA. We have introduced an automated program based on item response theory and determined the order of difficulty of the 71 training items in ReoGo-J. The strong correlation between the predicted ability and the shoulder-elbow-forearm items in FMA may be used to ameliorate post-stroke upper-extremity paralysis. Notably, the program allows for estimation of appropriate ReoGo-J tasks, enhancing clinical efficiency.Trial registration: https://www.umin.ac.jp/ctr/index-j.htm (UMIN000040127).

Association between the executive dysfunction and balance function in patients with stroke.

A previous study has shown an association between executive dysfunction (ED) and balance function in patients with stroke. However, it is unclear what factors mediate the association between ED and balance function. Therefore, the aim of this study was to investigate the association between ED and balance function and to identify mediating factors using mediation analysis. This study had a cross-sectional design. The study included 107 patients with stroke. This study was divided into two groups (ED and non-ED) using trail making test (TMT) part B. Two groups were compared for balance function (timed up and go test [TUGT] and Berg balance scale [BBS]) and other variables using paired test. In addition, partial correlation analysis with age, cognitive function as a control factor, and mediation analysis were also performed. The ED group (N=55) had significantly lower TUGT and BBS scores than the non-ED group (N=52). TMT part B correlated with TUGT (ρ=0.41), BBS (ρ=-0.33), and Brunnstrom recovery stage (BRS) lower limb (ρ=-0.22). The TUGT model of mediation analysis showed a significant indirect effect as a result of mediation of the BRS lower limb between TMT part B and TUGT. The BBS model showed a significant indirect effect as a result of mediation of the activities of daily living (ADL) motor function between TMT part B and BBS. ED and balance function were associated, and the degree of paralysis and ADL motor function were associated with them in patients with stroke.

Identifying the characteristics of patients with stroke who have difficulty benefiting from gait training with the hybrid assistive limb: a retrospective cohort study.

Robot-assisted gait training is effective for walking independence in stroke rehabilitation, the hybrid assistive limb (HAL) is an example. However, gait training with HAL may not be effective for everyone, and it is not clear who is not expected to benefit. Therefore, we aimed to identify the characteristics of stroke patients who have difficulty gaining benefits from gait training with HAL. We conducted a single-institutional retrospective cohort study. The participants were 82 stroke patients who had received gait training with HAL during hospitalization. The dependent variable was the functional ambulation category (FAC) that a measure of gait independence in stroke patients, and five independent [age, National Institutes of Health Stroke Scale, Brunnstrom recovery stage (BRS), days from stroke onset, and functional independence measure total score (cognitive items)] variables were selected from previous studies and analyzed by logistic regression analysis. We evaluated the validity of logistic regression analysis by using several indicators, such as the area under the curve (AUC), and a confusion matrix. Age, days from stroke onset to HAL initiation, and BRS were identified as factors that significantly influenced walking independence through gait training with HAL. The AUC was 0.86. Furthermore, after building a confusion matrix, the calculated binary accuracy, sensitivity (recall), and specificity were 0.80, 0.80, and 0.81, respectively, indicated high accuracy. Our findings confirmed that older age, greater degree of paralysis, and delayed initiation of HAL-assisted training after stroke onset were associated with increased likelihood of walking dependence upon hospital discharge.

Prevalence and predisposing factors of post-stroke complex regional pain syndrome: Retrospective case-control study

Poststroke complex regional pain syndrome (CRPS) is an important complication in stroke survivors. The identification of factors associated with post-stroke CRPS is important for preventive measures and early diagnosis. A total of 141 first-ever stroke survivors in the subacute stage were retrospectively analyzed. Demographic data, diagnosis time, duration of hospitalization, location of brain lesion, etiology, comorbidities, and blood test findings were investigated. Clinical data included Medical Research Council (MRC) grade, Fugl-Meyer assessment (FMA), National Institute for Health Stroke Scale (NIHSS), Berg Balance Scale (BBS). Among 141 patients with subacute stroke, 22 were diagnosed with CRPS, with a prevalence of 15.6%. The mean time to diagnosis was 38.6 (±16.5) days. The prevalence according to the degree of paralysis was 33.3% in MRC grades 0 and 1, 8.6% in grade 2, and 0% in grade 3 or higher. The incidence rates within 1 month after stroke were 1.42% and 22.47% between 1 and 3 months after stroke, respectively. The independent risk factors for CRPS were hospitalization duration and FMA, NIHSS, and BBS scores. The sensitivity and specificity of the NIHSS score for predicting post-stroke CRPS were 86.4% and 59.7%, respectively, with an optimal cutoff value of 7.5. CRPS of the affected upper limb in stroke patients is associated with stroke severity, including paralysis, and the incidence increases over time during the subacute phase. Additionally, having sufficient strength to move through a full range of motion against gravity had a protective effect against CRPS.

Pathophysiological and motor factors associated with collision avoidance behavior in individuals with stroke.

High collision rates and frequency of entering the opening from non-paretic sides are associated with collision in individuals with stroke. To identify factors associated with collision avoidance behavior when individuals with stroke walked through narrow openings. Participants with subacute or chronic stroke walked through a narrow opening and had to avoid colliding with obstacles. Multiple regression analyses were conducted with pathophysiology, motor function, and judgment ability as predictor variables; collision rate and frequency of entering the opening from non-paretic sides were outcome variables. Sixty-one eligible individuals with stroke aged 63±12 years were enrolled. Thirty participants collided twice or more and 37 entered the opening from the non-paretic side. Higher collision occurrence was associated with slower Timed Up and Go tests and left-right sway (odds ratios, 1.2 and 5.6; 95% confidence intervals, 1.1-1.3 and 1.3-28.2; p = .008 and.025, respectively). Entering from non-paretic sides was associated with lesions in the thalamus, left-sided hemiplegia, and Brunnstrom stage 3 or lower (odds ratios, 6.6, 8.7, and 6.7; 95% confidence intervals, 1.3-52.5, 2.5-36.5, and 1.2-57.5; and p = .038,.001, and.048, respectively). Walking ability is associated with avoiding obstacle collision, while pathophysiological characteristics and degree of paralysis are associated with a preference for which side of the body enters an opening first. Interventions to improve walking ability may improve collision avoidance. Avoidance behavior during intervention varies depending on the lesion position.

THE IMPORTANCE OF SUGAMMADEX AT POSTOPERATIVE RESIDUAL NEUROMUSCULAR BLOCK

Introduction: postoperative residual neuromuscular blockade is the postoperative muscle paralysis caused by incomplete or null antagonism of neuromuscular blocking agents. Post-surgical residual paralysis (PORP) has a high incidence and may cause adverse effects, increasing postoperative morbidity and mortality. The gold standard for complete reversal of neuromuscular blockade is a T4/T1 ratio of 0.9. Small degrees of paralysis are associated with an increased risk of postoperative pulmonary complications. Recent research indicates that residual neuromuscular blockade is a significant risk factor for patient safety. Objective: to detail the current information related to postoperative residual paralysis, in addition to explaining the use and characteristics of sugammadex in its reversal. Methodology: a total of 45 articles were analyzed in this review, including review and original articles, as well as clinical cases, of which 35 bibliographies were used because the other articles were not relevant for this study. The sources of information were PubMed, Google Scholar and Cochrane; the terms used to search for information in Spanish, Portuguese and English were: postoperative residual neuromuscular block, postoperative muscle weakness, sugammadex, anticholinesterase inhibitors. Results: Neuromuscular block occurs due to muscle fragility in the postoperative period due to antagonism, which produces a decrease in the musculature of the upper and lower airways. When this phase is properly managed, extubation delays are reduced, and postoperative pulmonary complications are reduced. Sugammadex is a relaxant that decreases the possibility of persistent neuromuscular paralysis; as neuromuscular blockade increases, contraction decreases. Therefore, when this drug is used, the risk of adverse effects, mostly respiratory, is avoided. This drug inactivates rocuronium, and the adverse effects it presents (although very infrequent) are dysgeusia, cough, grimacing or increased secretion through the endotracheal tube. Conclusions: sugammadex is suggested to be used before neostigmine, although it should be used in patients with high risk of postoperative complications, such as patients over 80 years of age or with post cardiothoracic surgery. However, sugammadex reverses neuromuscular blockade more rapidly, with a decrease in the frequency of residual neuromuscular blockade and postoperative pulmonary complications such as pneumonias. A point to consider is that sugammadex is more expensive and is usually accompanied by higher presentations of adverse effects. KEY WORDS: sugammadex, paralysis, residual, postoperative, antagonism, neuromuscular.

A study on the magnitude of neural tube defects among newborns delivered at a tertiary care hospital

Background: In a developing fetus during the stages of embryogenesis, various congenital malformations tend to occur, among which neural tube defects (NTDs) are one of the more serious conditions. They result due to the failure of the closure of the neural tube along its length, which may lead to cranial or spinal defects. This may present with the wastage of the pregnancy as a stillbirth or, in cases of live birth, with serious complications and associated disabilities such as varying degrees of paralysis, neurogenic bladder, and incontinence of urine and stools and hydrocephalus. Numerous risk factors have been linked with the occurrence of NTDs such as genetic susceptibility, low socioeconomic status, exposure to teratogens such as methotrexate, trimethoprim, aminopterin, and valproate and other antiepileptic drugs during pregnancy, deficiency of vitamins like folate and B12 in females and the risk of recurrence of NTDs in future pregnancies to a female with a past pregnancy having NTD. Aims and Objectives: The present study aims to determine the prevalence and types of NTDs among newborns and to study associated anomalies among them with NTDs. Materials and Methods: General Hospital Palanpur, a tertiary care hospital connected with Banas Medical College and Research Institute, Palanpur, was the site of the study. In the current study, the total number of births was recorded during a 3-year period from 2019 to 2021, and total NTDs data were gathered and analyzed to determine the prevalence of NTDs at the hospital, as well as the various types and related abnormalities. Results: The total number of deliveries in the span of 2019–2021 was 3437 of which 21 cases of NTDs were noted. Out of 21, twelve were male and nine were female, which makes it 57.14% male preponderance compared to females. Moreover, the prevalence of NTDs comes out to be 6.1/1000 births in the span of 3 years. Furthermore, this study suggested that among the NTDs, 61.90% were meningomyelocele which makes it more prevalent than encephalocele and spina bifida. It is also seen that NTDs were more common in multigravida females with gravida <3 and gravida ≥3 (28.57% and 47.61%, respectively) and in multipara females with parity <3 and ≥3 (80.95% and 19.04%, respectively). Conclusion: The prevalence of NTDs is not uncommon in our sector, which needs to be addressed by periconceptional folic acid supplementation for all women of childbearing age.

SLEEP MONITORING FOR INDIVIDUALS WITH SPINAL CORD INJURY USING CONTACT-FREE BED SENSORS

Sleep disorders are common in individuals with spinal cord injury (SCI), and contact-free bed sensors can detect these problems. This study examined whether these sensors apply to these individuals, especially at the cervical level, with a high degree of paralysis and limited mobility. First, we investigated whether their motion characteristics affect heart rate (HR), sleep latency, and sleep stage. We compared three commercial contact-free sensors: Emfit QS (Emfit Ltd., Finland), EarlySense Live (EarlySense Ltd., Israel), and SCA11H (Murata Manufacturing Ltd., Japan) with polysomnography (PSG)—a standard for sleep assessment. Then, we monitored the sleep on hospital and home beds and observed the percentages of timestamps and average HR and respiration rate (RR) recorded on the three devices. Compared with PSG, Emfit QS and EarlySense Live recorded an earlier sleep onset. Furthermore, the mean HR recorded by Emfit QS, EarlySense Live, and SCA11H differed by 0 to 8 beats per minute (BMP). In hospital beds, the collection rate for all three sensors was higher than 98% and HR, and RR differed by only 1.1[Formula: see text]BPM and 0.5[Formula: see text]BPM, respectively. Contrastingly, the rates differed by 13.7[Formula: see text]BPM and 9.9[Formula: see text]BMP at home, respectively. While these sensors differed from PSG and their data coverage rate was low, they can help clarify sleep disorders. Continuous sleep monitoring is essential for individuals with SCI, and sleep-monitoring devices are expected to contribute to this and help improve their quality of life.

Prediction of lower extremity strength by nerve conduction study in cauda equina syndrome.

An electrodiagnostic test is more useful than the lower extremity isometric strength test for objectively determining the degree of nerve damage and prognosis in cauda equina syndromes (CES). This study evaluated the correlation between nerve conduction study (NCS) parameters and the lower extremity isometric strength and manual muscle test (MMT) grades.The isometric strengths of knee extension (KE), ankle dorsiflexion (ADF), and ankle plantarflexion (APF) were measured. NCS parameters, MMT, and isometric strength of femoral, peroneal, and tibial nerves were evaluated, including their correlations with each other. A regression equation between the isometric strength and compound muscle action potential (CMAP) amplitudes was derived and cutoff values were used to confirm boundary values of strength and amplitude between the MMT grades.KE isometric strength and femoral nerve CMAP amplitude were significantly correlated (r = 0.738, P < .001). ADF isometric strength and peroneal nerve CMAP amplitude were significantly correlated (tibialis anterior, r = 0.707, P < .001). KE (r = 0.713, P < .001), ADF (r = 0.744, P < .001), and APF (r = 0.698, P < .001) isometric strengths were correlated with the MMT grades. For the regression curve, the second-order curve was more reasonable than the first-order curve. Cutoff femoral nerve CMAP amplitude and isometric strength cutoff values were ≥2.05 mV and 17.3, respectively, for MMT grades 2 to 3 and 2.78 ± 1.08 and 20.8 ± 9.33, respectively, for grade 3.The isometric strengths of the KE, ADF, and APF and the CMAP amplitude of the electrophysiologic parameters were correlated in CES patients and a significant correlation with MMT grade was also identified. Accordingly, it is possible to identify the precise neurological condition, objectively evaluate the degree of paralysis and disability, and determine the quantitative muscle strength from MMT in order to establish an appropriate rehabilitation treatment plan.

Longitudinal electrophysiological changes after mesenchymal stem cell transplantation in a spinal cord injury rat model.

Transcranial electrically stimulated motor-evoked potentials (tcMEPs) are widely used to evaluate motor function in humans and animals. However, the relationship between tcMEPs and the recovery of paralysis remains unclear. We previously reported that transplantation of mesenchymal stem cells to a spinal cord injury (SCI) rat model resulted in various degrees of recovery from paraplegia. As a continuation of this work, in the present study, we aimed to establish the longitudinal electrophysiological changes in this SCI rat model after mesenchymal stem cell transplantation. SCI rats were established using the weight-drop method. The model rats were transvenously transplanted with two types of mesenchymal stem cells (MSCs), one derived from rat cranial bones and the other from the bone marrow of the femur and tibia bone, 24 h after SCI. A phosphate-buffered saline (PBS) group that received only PBS was also created for comparison. The degree of paralysis was evaluated over 28 days using the Basso-Beattie-Bresnahan (BBB) scale and inclined plane task score. Extended tcMEPs were recorded using a previously reported bone-thinning technique, and the longitudinal electrophysiological changes in tcMEPs were investigated. In addition, the relationship between the time course of recovery from paralysis and reappearance of tcMEPs was revealed. The appearance of the tcMEP waveform was earlier in MSC-transplanted rats than in PBS-administered rats (earliest date was 7 days after SCI). The MEP waveforms also appeared at approximately the same level on the BBB scale (average score, 11 points). Ultimately, this study can help enhance our understanding of the relationship between neural regeneration and tcMEP recording. Further application of tcMEP in regenerative medicine research is expected.

Comparative Study of Circumferential Decompression and Posterior Decompression in Palliative Surgery for Metastatic Thoracic Spinal Tumors.

This was a case-control study. The present study aimed to evaluate the significance of circumferential tumor resection around the spinal cord in palliative decompression surgery for patients with metastatic spinal cord compression (MSCC) in the thoracic spine. Although the benefits of palliative surgery for MSCC are well known, the significance of circumferential tumor resection with cord compression has not yet been clarified. We retrospectively compared the outcomes of 45 and 34 patients with incomplete paralysis of modified Frankel grade B-D caused by MSCC with anterior cord compression (epidural spinal cord compression grade ≥2) treated at 2 different university hospitals (H1 and H2, respectively). All patients in H1 hospital underwent posterior decompression only, while all patients in H2 hospital underwent full circumferential decompression. We analyzed factors that affect the postoperative ambulatory status. evaluated by the modified Frankel classification. No significant differences were observed in the epidural spinal cord compression grade, spinal instability neoplastic score, new Katagiri score, revised Tokuhashi score, or postoperative survival between patients in H1 and H2 hospitals. A multivariable logistic regression analysis identified preoperative radiotherapy [odds ratio (OR): 0.23, 95% confidential interval (CI): 0.056-0.94] as a negative risk factor and postoperative chemotherapy (OR: 5.9, 95% CI: 1.3-27.0) as a positive risk factor for an improved ambulatory status. Five and 6 patients in H1 and H2 hospitals, respectively, showed deterioration in the ambulatory status. An older age (OR: 1.1, 95% CI: 1.0-1.2) and preoperative radiotherapy (OR: 10.3, 95% CI: 1.9-55.4) were extracted as significant independent risk factors for deterioration in the ambulatory status. Circumferential decompression did not improve the clinical results of patients regardless of the degree of paralysis. Preoperative radiotherapy interfered with the recovery of paralysis, and postoperative chemotherapy improved the ambulatory status. Clinical outcomes did not significantly differ between total circumferential decompression and posterior decompression, although further validation in a small number of cases is needed, such as patients with Frankel grade D.

Acute flaccid rhombencephalomyelitis with radiculitis in a child with an enterovirus A71 infection seen for the first time in Denmark: a case report

BackgroundAcute flaccid myelitis is a serious condition of the spinal cord. More than 80% of patients experience a mild respiratory illness or fever consistent with a viral infection prior to acute flaccid myelitis development. Enterovirus A71 is known to circulate in Denmark, and has previously been associated with severe neurological symptoms. In this case report we describe acute flaccid rhombencephalomyelitis with radiculitis in an infant with an enterovirus infection.Case presentationThe 8-month-old male of Asian origin presented with fever and gastrointestinal symptoms, followed by severe neurological deficits such as flaccid paralysis of the neck and upper extremities. An initial magnetic resonance imaging scan of the brain was normal, and the boy was treated for encephalitis. A follow-up magnetic resonance imaging scan of the brain and spinal cord 1 week later showed the development of pathological symmetrical gray matter hyperintensity lesions on T2-weighted images in the brainstem and upper medulla spinalis, and nerve enhancement in the terminal thread of the spinal cord and the cervical roots; findings consistent with rhombencephalomyelitis with radiculitis causing flaccid paralysis. Enterovirus A71 was detected in both nasopharyngeal and fecal specimens. Other differential diagnostic etiologies of viral and bacterial encephalitis, including poliovirus, were excluded.ConclusionsThis is the first case in Denmark of a patient diagnosed with acute flaccid rhombencephalomyelitis strongly linked to an enterovirus A71 infection. This case emphasizes the diagnostic importance of combining a history of respiratory and/or gastrointestinal illness, fever, and delayed onset of varying degrees of paralysis with progressive characteristic spinal and brain lesions. Analysis of respiratory, fecal, and cerebrospinal samples for the presence of enterovirus, and eliminating other differential pathogens, is essential to confirm the diagnosis.

Функціональний стан нижніх кінцівок у хворих з ортопедичними проявами спінальних дизрафій

Спінальні дизрафії є важливою причиною статико-локомоторних порушень у дітей. Залежно від рівня ураження спинного мозку виникає різний ступінь паралічу чи парезу нижніх кінцівок, порушення функції тазових органів, деформації кінцівок і хребта, що значною мірою впливає на якість життя дитини та її можливість до пересування та обслуговування. Мета: залежно від рівня функціональної недостатності нижніх кінцівок оцінити здатність до пересування хворих із наслідками відкритих форм спінальних дизрафій. Матеріали та методи. Матеріал дослідження становили 81 пацієнт віком від 5 до 21 року (середній вік 8 років 10 місяців): у 69 пацієнтів спостерігався парапарез нижніх кінцівок, у 12 — монопарез. Визначення рівня нейросегментарного ураження спинного мозку проводилося згідно з класифікацією Sharrard`s (1964) у модифікації Bartonek et al. (1999). Здатність до пересування оцінювали за класифікацією Hoffer et al. (1973). Результати та обговорення. Всіх хворих, включених у дослідження, розподілено відповідно до рівня функціональної м’язової сили на 5 клінічних груп із визначеним рівнем функціональної м’язової сили за класифікацією Sharrard’s (1964) у модифікації Bartonek et al. (1999), проведено оцінку фактичного ступеня пересування хворих за Hoffer (1973). Порівняння отриманого фактичного ступеня пересування до теоретично очікуваного ступеня пересування пацієнтів показало, що діти з однаковим рівнем функціональної недостатності нижніх кінцівок не завжди досягають очікуваного ступеня пересування, а залежно від впливу супутніх факторів, таких як інтелектуальний (розумовий) рівень дитини, прогресування гідроцефалії, ожиріння, тяжкість ортопедичної патології, наявність спастичності та інші, можуть досягати як вищого, так і гіршого ступеня пересування. Висновки. Рівень нейросегментарного ураження спинного мозку, що визначає рівень м’язової функції нижніх кінцівок, є важливим фактором у здатності до пересування хворих із наслідками спінальних дизрафій. Пацієнти з однаковим рівнем втрати м’язової функції не завжди досягають очікуваного рівня пересування.

片麻痺患者用歩行訓練リハビリテーションロボットにおける強化学習を用いたアシスト量自動調整システムの開発

We have developed a gait training rehabilitation robot “Akita Trainer” for hemiplegic patients. It has servomotors attached to the hip and knee joints of the exoskeleton, and driving it enables gait rehabilitation of the paralyzed people. As its core systems, we developed a variable assist system and an automatic assist adjustment system. The variable assist system based on compliance control can change the stiffness parameter of “Akita Trainer” to provide assist torque according to the degree of paralysis. The automatic assist adjustment system uses reinforcement learning to change the stiffness parameter to the optimal value for the paralyzed people while using this robot. We conducted an experiment with three healthy subjects to validate the combined system of both. We set up two walking patterns: , normal walking and pseudo-hemiplegic walking assuming right hemiplegia. The participants walked for 10 minutes on the treadmill at a speed of 0.8 km/h. The amount of assistance decreased for normal walking and increased for pseudo-hemiplegic walking, indicating that the optimal amount of assistance can be provided according to the walking patterns. By using this system, it is possible to perform gait rehabilitation with the optimal assist torque for the hemiplegic people.

Videofluoroscopic Swallow Study Findings and Correlations in Infancy of Children with Cerebral Palsy.

Cerebral palsy (CP) in infants can affect global motor function and lead to swallowing difficulties. This study aims to characterize oral and pharyngeal swallowing dynamics in infancy of patients later diagnosed with CP and to determine if swallow study performance in early infancy is associated with later CP severity and characteristics. This is a retrospective chart review of infants who underwent videofluoroscopic swallow studies (VFSS) between 6/2008 and 10/2018 at a tertiary children's hospital, and were later diagnosed with CP. Demographic data, CP characteristics and metrics, and VFSS findings were collected and analyzed. There were 66 patients included in this study. The average age at the time of VFSS was 4 months (range: 0.3-12 months), 42% of patients were female, and 50% of patients were born premature. In our sample, 86% of patients presented with oral dysphagia, and 76% with pharyngeal dysphagia. Laryngeal penetration in isolation was seen in 39% of patients, and tracheal aspiration was seen in 38% of patients. Of these tracheal aspiration events, 64% were silent. At the time of VFSS, 58% of patients had a nasogastric tube, 12% had a gastrostomy tube, and 3% had a prior hospitalization for pneumonia. Rates of penetration and aspiration in early infancy did not consistently correlate with prematurity, type of CP (spastic, non-spastic, or mixed), degree of paralysis (quadriplegic, hemiplegic, or diplegic), or severity of Gross Motor Function Classification System (GMFCS) score. While there was not a consistent correlation of swallowing dynamics in infancy with later gross motor categorizations of CP, the results of this retrospective review highlight the essential role of early clinical and videofluoroscopic swallowing evaluations to identify oral and pharyngeal swallowing dysfunction in this patient population.

The Need to Tic.

Botulinum toxin (BoNT) injections are commonly used to treat focal motor and vocal tics. However, rigorous studies on BoNT efficacy and tolerability in this field are lacking.1 In our experience, BoNT is effective and well-tolerated in the treatment of tics, and the discontinuation rate due to inefficacy is very low. Importantly, the mechanism of BoNT-related tic improvement remains unclear. Kwak et al.2 suggested that BoNT injections might lead to a reduction in both the intensity of premonitory urges and tics in patients with Tourette syndrome (TS), as noted in 21/25 of their cases. In contrast to this observation, we report 3 patients with TS who decided to discontinue BoNT because the resulting muscle paralysis prevented tic occurrence and the subsequent relief of their premonitory urges. Patient 1 is a 27-year-old female presenting with simple and complex motor tics as well as a history of simple vocal tics (coughing, sniffing). The current phenomenology includes head jerks and eye movements to the left, eye winking, eyebrow raising, frowning, and pushing the tongue up in her mouth. She also reported to have an obsessive personality with superstitious beliefs. We treated her with BoNT injections only once, delivering a total dose of 60 U of AboBoNT/A to the frontalis, the corrugator and the orbicularis oculi muscles bilaterally. Patient 2 is a 43-year-old male with simple motor tics involving his neck (side-to-side head jerks) and shoulder since early childhood and occasional vocal tics (coughing). He describes himself as a perfectionist but denies obsessive–compulsive features. He was treated once with a total dose of AboBoNT/A 100 U, 50 U in each splenius capitis. Patient 3 is a 25-year old female who shows simple (e.g. eyebrow movements, eye rolling) and complex (e.g. stomping legs on the floor) motor tics, and simple phonic tics (e.g. repetitive coughing). She received BoNT injections only once in both orbicularis oculi and frontalis muscles, for a total dose of 36 MU of IncoBoNT/A. Although BoNT led to a substantial improvement of the targeted tics in all 3 patients, they declined to pursue BoNT treatment due to increased salience of premonitory urges. They felt frustrated for still experiencing the need to tic in the treated areas, without being able to do so due to BoNT-induced muscle weakness. The pathophysiology of sensory symptoms associated with tic disorders is poorly understood. The negative reinforcement hypothesis views tics as operant behaviors to alleviate the aversive experience of premonitory urges.3 BoNT prevents tics by inducing a certain degree of paralysis in the injected muscles. It might also play a role in disrupting the impaired sensory feedback in tic disorders, therefore reducing the intensity of premonitory sensations, as previously reported.2 However, not all patients may share this improvement, and indeed the only randomized control study previously performed to assess BoNT efficacy for treating tics in primary tic disorders also documented a case where there was an increase of premonitory urges, despite the reduction of motor tics.4 Of note, a similar dissociation between tic improvement and persistence of aversive somatic experiences (“sense of inner tension”) was also previously reported in an adult who was treated with bilateral deep brain stimulation of the internal globus pallidus.5 Taken together, our cases highlight the substantial heterogeneity of tic disorders, particularly with regard to treatment response, and characteristically illustrate that in some patients we can successfully treat the tic, but not the need to tic. (1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique. G.D.L.: 1B, 1C, 3A F.M.: 1B, 1C, 3A C.G.:1B, 3A, 3B K.B.: 1A, 3B Dr. Di Lazzaro and Dr. Magrinelli contributed equally to this work. Ethical Compliance Statement: The authors confirm that the approval of an institutional review board was not required for this work. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Funding Sources and Conflicts of Interest: The authors report no sources of funding and no conflicts of interest. Financial Disclosures for Previous 12 Months: Giulia Di Lazzaro and Francesca Magrinelli are supported by the EAN research fellowship 2020. Christos Ganos holds research grants from the VolkswagenStiftung (Freigeist Fellowship) and the German Parkinson Society and was also supported by the Deutsche Forschungsgemeinschaft (GA2031/1-1and GA2031/1–2). Kailash P. Bhatia holds research grants from EU Horizon 2020 and has received honoraria to speak at meetings or to attend advisory boards from Ipsen, Cavion, Allergan, Teva Lundbeck, and Bial pharmaceutical companies. He also receives royalties from Oxford University Press and a stipend for MDCP editorship.

Corticospinal-motor neuronal plasticity promotes exercise-mediated recovery in humans with spinal cord injury.

Rehabilitative exercise in humans with spinal cord injury aims to engage residual neural networks to improve functional recovery. We hypothesized that exercise combined with non-invasive stimulation targeting spinal synapses further promotes functional recovery. Twenty-five individuals with chronic incomplete cervical, thoracic, and lumbar spinal cord injury were randomly assigned to 10 sessions of exercise combined with paired corticospinal-motor neuronal stimulation (PCMS) or sham-PCMS. In an additional experiment, we tested the effect of PCMS without exercise in 13 individuals with spinal cord injury with similar characteristics. During PCMS, 180 pairs of stimuli were timed to have corticospinal volleys evoked by transcranial magnetic stimulation over the primary motor cortex arrive at corticospinal-motor neuronal synapses of upper- or lower-limb muscles (depending on the injury level), 1-2 ms before antidromic potentials were elicited in motor neurons by electrical stimulation of a peripheral nerve. Participants exercised for 45 min after all protocols. We found that the time to complete subcomponents of the Graded and Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) and the 10-m walk test decreased on average by 20% after all protocols. However, the amplitude of corticospinal responses elicited by transcranial magnetic stimulation and the magnitude of maximal voluntary contractions in targeted muscles increased on overage by 40-50% after PCMS combined or not with exercise but not after sham-PCMS combined with exercise. Notably, behavioural and physiological effects were preserved 6 months after the intervention in the group receiving exercise with PCMS but not in the group receiving exercise combined with sham-PCMS, suggesting that the stimulation contributed to preserve exercise gains. Our findings indicate that targeted non-invasive stimulation of spinal synapses might represent an effective strategy to facilitate exercise-mediated recovery in humans with different degrees of paralysis and levels of spinal cord injury.

Activating Resident Neural Precursor Cells in the Spinal Cord to Promote Neural Repair

Within the mammalian spinal cord there are two distinct populations of neural precursor cells: neural stem and progenitor cells (NSPCs) and oligodendrocyte progenitor cells (OPCs). NSPCs are located within the periventricular zone of the spinal cord and are relatively quiescent and non‐neurogenic under homeostatic conditions. OPCs are located throughout the grey and white matter of the spinal cord and give rise to new oligodendrocytes throughout life. Both of these populations are activated following injury, however, their response is not sufficient for functional recovery. We propose that enhancing resident precursor activation is a promising approach to improve structural and functional outcomes following SCI. The FDA‐approved drug metformin (MET) has demonstrated efficacy in promoting improved outcomes in the injured brain through pleiotropic effects including: decreased inflammation, enhanced precursor cell activation and increased neurogenesis and oligogenesis. Here, we seek to establish the influence of MET treatment on NSPC and OPC populations and explore whether MET can improve functional recovery following injury in the spinal cord. Our cellular data reveal that in uninjured animals, MET treatment significantly expands the NSPC pool in females, but not males; increases neurogenesis in males only and enhances oligogenesis across both sexes. Conversely, we observed no effect of MET treatment on the number of OPCs in uninjured mice, irrespective of sex. To test the efficacy of MET treatment following injury, we used two distinct models: (1) a dorsal column injury in the thoracic spinal cord (SCI), and (2), a model of multiple sclerosis (experimental autoimmune encephalomyelitis, EAE). In both models, MET was delivered to mice immediately following injury and for 14 days. Following SCI, mice were tested on a skilled walking test on post‐injury days (PID) 7 and 14. While all mice showed a significant deficit on PID7, by PID14, MET treated animals were not significantly impaired relative to pre‐injury performance and naive controls. In the EAE model, we evaluated the efficacy of MET treatment through both clinical scoring (based on degree of paralysis) and gait analysis. EAE resulted in significant clinical deficits 14 days following induction, which were mitigated in mice that received MET. Additionally, our gait analysis revealed improved metrics in MET treated mice. Across both injury models we observed significantly reduced inflammation. Taken together, our results support MET as a viable therapeutic strategy to expand and enhance NSPCs, improve the response of OPCs and support functional recovery following spinal cord injury.Support or Funding InformationCanadian Institute of Health ResearchMedicine by Design

Novel Antidotal Treatment of Botulism Using an FDA‐Approved Small Molecule

Botulinum neurotoxins (BoNTs) are exceedingly potent neuroparalytic toxins which block release of neurotransmitter from motor nerve terminals, causing respiratory failure at lethal doses. The only treatment for botulism is post‐exposure prophylaxis with antitoxin. However, antitoxin is most effective when given prior to symptomatic emergence, and consequently 70% of symptomatic patients require artificial ventilation for a median of two weeks. The voltage‐gated potassium channel antagonist 3,4‐diaminopyridine (DAP) has been proposed as a symptomatic treatment to mitigate muscle weakness in botulism patients. However, experimental support for this hypothesis is lacking.To test the efficacy of DAP in treating toxic signs of botulism, we first evaluated concentration‐dependent effects of DAP on synaptic transmission and muscle function in mouse hemidiaphragm preparations following intoxication by BoNT serotypes A, B or E. For all serotypes, DAP increased quantal content and restored muscle contraction, with effect sizes that were inversely proportional to the degree of paralysis. Based on these findings, we evaluated the effects of human‐equivalent doses of DAP in mice intoxicated with the same BoNT serotypes. In a sublethal intoxication model, DAP transiently increased respiratory function at multiple time points for all serotypes. In lethal challenges with BoNT/A, repeated administration of DAP sustained respiratory function and prolonged survival throughout the treatment period. These findings suggested that DAP could have antidotal efficacy if continuously delivered. To test for antidotal capability, DAP was continuously infused at nontoxic levels in rats intoxicated with 2 LD50 of BoNT/A, starting after signs of botulism emerged. DAP enabled 100% survival, whereas saline‐treated rats died in 2.8 days. Infusion was stopped at two weeks once respiratory signs of botulism resolved, and rats remained healthy and active through study end at three weeks, without symptomatic rebound. Following euthanasia, electrophysiological characterization revealed a large fraction of phrenic endplates that continued to exhibit impaired neuromuscular transmission, despite the apparent absence of physiological signs of botulism. These data suggest that treatment with DAP allowed for the emergence of compensatory changes in neuromuscular function that promoted physiological recovery. Not only do the underlying mechanisms represent fertile ground for therapeutic exploitation, but they are also important for understanding regenerative responses following transient chemical denervation of the respiratory system.These studies indicate that DAP has unique potential to improve respiratory function during botulism. Furthermore, they demonstrate the first antidotal treatment of type A botulism in vivo. We are currently preparing to evaluate the effects of DAP on respiratory function and intensity and duration of supportive care in patients suffering natural and iatrogenic botulism.Support or Funding InformationThis project was funded by the Defense Threat Reduction Agency and NIH (R01A193504); and supported by appointments to the Postgraduate Research Participation Program at USAMRICD administered by the Oak Ridge Institute for Science and Education.

Attempt to Silence Genes of the RNAi Pathways of the Root-Knot Nematode, Meloidogyne incognita Results in Diverse Responses Including Increase and No Change in Expression of Some Genes.

Control of plant-parasitic nematodes (PPNs) via host-induced gene silencing (HIGS) involves rational selection of genes and detailed assessment of effects of a possible knockdown on the nematode. Some genes by nature may be very important for the survival of the nematode that knockdown may be resisted. Possible silencing and effects of 20 such genes involved in the RNA interference (RNAi) pathways of Meloidogyne incognita were investigated in this study using long double-stranded RNAs (dsRNAs) as triggers. Two of the genes, ego-1 and mes-2, could not be knocked down. Expression of six genes (xpo-1, pash-1, xpo-2, rha-1, ekl-4, and csr-1) were significantly upregulated after RNAi treatment whereas for 12 of the genes, significant knockdown was achieved and with the exception of mes-2 and mes-6, RNAi was accompanied by defective phenotypes in treated nematodes including various degrees of paralysis and abnormal behaviors and movement such as curling, extreme wavy movements, and twitching. These abnormalities resulted in up to 75% reduction in infectivity of a tomato host, the most affected being the J2s previously treated with dsRNA of the gfl-1 gene. For 10 of the genes, effects of silencing in the J2s persisted as the adult females isolated from galls were under-developed, elongated, and transparent compared to the normal saccate, white adult females. Following RNAi of ego-1, smg-2, smg-6, and eri-1, reduced expression and/or the immediate visible effects on the J2s were not permanent as the nematodes infected and developed normally in tomato hosts. Equally intriguing was the results of RNAi of the mes-2 gene where the insignificant change in gene expression and behavior of treated J2s did not mean the nematodes were not affected as they were less effective in infecting host plants. Attempt to silence drsh-1, mut-7, drh-3, rha-1, pash-1, and vig-1 through HIGS led to reduction in nematode infestation by up to 89%. Our results show that genes may respond to RNAi knockdown differently so an exhaustive assessment of target genes as targets for nematode control via RNAi is imperative.