Adjunctive hyperbaric oxygen therapy for spinal cord ischemia after complex aortic repair.

OBJECTIVE: Spinal cord ischemia (SCI) with paraplegia or paraparesis is a devastating complication of complex aortic repair (CAR). Treatment includes cerebrospinal fluid drainage, maintenance of hemoglobin concentration (>10 g/L), and elevating mean arterial blood pressure. Animal and human case series have reported improvements in SCI outcomes with hyperbaric oxygen therapy (HBOT). We reviewed our center's experience with HBOT as a rescue treatment for spinal cord ischemia post-CAR in addition to standard treatment. METHODS: A retrospective review of the University Health Network's Hyperbaric Medicine Unit treatment database identified HBOT sessions for patients with SCI post-CAR between January 2013 and June 2021. Mean estimates of overall motor function scores were determined for postoperative, pre-HBOT, post-HBOT (within 4 hours of the final HBOT session), and at the final assessment (last available in-hospital evaluation) using a linear mixed model. A subgroup analysis compared the mean estimates of overall motor function scores between improvement and non-improvement groups at given timepoints. Improvement of motor function was defined as either a ≥2 point increase in overall muscle function score in patients with paraparesis or an upward change in motor deficit categorization (para/monoplegia, paraparesis, and no deficit). Subgroup analysis was performed by stratifying by improvement or non-improvement of motor function from pre-HBOT to final evaluation. RESULTS: Thirty patients were treated for SCI. Pre-HBOT, the motor deficit categorization was 10 paraplegia, three monoplegia, 16 paraparesis, and one unable to assess. At the final assessment, 14 patients demonstrated variable degrees of motor function improvement; eight patients demonstrated full motor function recovery. Seven of the 10 patients with paraplegia remained paraplegic despite HBOT. The estimated mean of overall muscle function score for pre-HBOT was 16.6 ± 2.9 (95% confidence interval [CI], 10.9-22.3) and for final assessment was 23.4 ± 2.9 (95% CI, 17.7-29.1). The estimated mean difference between pre-HBOT and final assessment overall muscle function score was 6.7 ± 3.1 (95% CI, 0.6-16.1). The estimated mean difference of the overall muscle function score between pre-HBOT and final assessment for the improved group was 16.6 ± 3.5 (95% CI, 7.5-25.7) vs -4.9 ± 4.2 (95% CI, -16.0 to 6.2) for the non-improved group. CONCLUSIONS: HBOT, in addition to standard treatment, may potentially improve recovery in spinal cord function following SCI post-CAR. However, the potential benefits of HBOT are not equally distributed among subgroups.

Development and Validation of Wheelchair-Based Yoga Module for Individuals with Paraplegia.

Spinal cord injury causes temporary or permanent loss of motor, sensory, or autonomic functions, leading to long-term impairments that are not only confined to physical attributes but also restrict individuals' participation in major domains of life. Around 60%-80% of individuals with spinal cord injuries depend on a wheelchair for mobility. Numerous studies have reported yoga's beneficial role in alleviating spinal cord injury symptoms; however, a validated wheelchair-based yoga module was unavailable. Thus, the present study aimed to develop and validate a wheelchair-based yoga module that comprises a printed protocol for individuals with paraplegia. The study was conducted in four phases: The first three phases were the steps for the formulation of a wheelchair-based yoga module, and in the last phase the content validity of the designed module was determined by a panel of 10 experts, who were asked to rate the preliminary module for its necessity and relevance using a Likert scale. A total of 17 yoga practices with high content validity were included in the final wheelchair-based yoga module, and 10 practices with lower content validity were excluded from the designed module. Data analysis revealed the mean content validation index of the designed module to be 0.81. This study concludes that the formulated wheelchair-based yoga module is valid for individuals with paraplegia. However, future studies need to be conducted to determine the protocol's feasibility and effectiveness.

Paving a way to treat spastic paraplegia 50.

Spastic paraplegia 50 (SPG50) is a rare neurodegenerative disease caused by loss-of-function mutations in AP4M1. There are no effective treatments for SPG50 or any other type of SPG, and current treatments are limited to symptomatic management. In this issue of the JCI, Chen et al. provide promising data from preclinical studies that evaluated the efficacy and safety profiles of an AAV-mediated AP4M1 gene replacement therapy for SPG50. AAV/AP4M1 gene replacement partly rescued functional defects in SPG50 cellular and mouse models, with acceptable safety profiles in rodents and monkeys. This work represents a substantial advancement in therapeutic development of SPG50 treatments, establishing the criteria for taking AAV9/AP4M1 gene therapy to clinical trials.

Intrathecal AAV9/AP4M1 gene therapy for hereditary spastic paraplegia 50 shows safety and efficacy in preclinical studies.

Spastic paraplegia 50 (SPG50) is an ultrarare childhood-onset neurological disorder caused by biallelic loss-of-function variants in the AP4M1 gene. SPG50 is characterized by progressive spastic paraplegia, global developmental delay, and subsequent intellectual disability, secondary microcephaly, and epilepsy. We preformed preclinical studies evaluating an adeno-associated virus (AAV)/AP4M1 gene therapy for SPG50 and describe in vitro studies that demonstrate transduction of patient-derived fibroblasts with AAV2/AP4M1, resulting in phenotypic rescue. To evaluate efficacy in vivo, Ap4m1-KO mice were intrathecally (i.t.) injected with 5 × 1011, 2.5 × 1011, or 1.25 × 1011 vector genome (vg) doses of AAV9/AP4M1 at P7-P10 or P90. Age- and dose-dependent effects were observed, with early intervention and higher doses achieving the best therapeutic benefits. In parallel, three toxicology studies in WT mice, rats, and nonhuman primates (NHPs) demonstrated that AAV9/AP4M1 had an acceptable safety profile up to a target human dose of 1 × 1015 vg. Of note, similar degrees of minimal-to-mild dorsal root ganglia (DRG) toxicity were observed in both rats and NHPs, supporting the use of rats to monitor DRG toxicity in future i.t. AAV studies. These preclinical results identify an acceptably safe and efficacious dose of i.t.-administered AAV9/AP4M1, supporting an investigational gene transfer clinical trial to treat SPG50.

A Case of Paraplegia Treated with Cerebrospinal Fluid Drainage and Permissive Hypertension after Graft Replacement of the Ascending Aorta and the Total Aortic Arch for Acute Aortic Dissection Stanford Type A.

Paraplegia after an operation for acute aortic dissection Stanford type A (AADA) is fairly uncommon, and there is no consensus about optimal treatment. We present a case in which cerebrospinal fluid drainage (CSFD) and permissive hypertension were used for treatment of paraplegia. When the patient showed complete bilateral paraplegia after operation for AADA, we immediately began CSFD and maintained mean arterial blood pressure at over 90 mmHg. His neurological deficit gradually recovered, and he was eventually able to walk without support. The combination of CSFD and permissive hypertension could be a first-line emergent treatment for postoperative paraplegia after AADA surgery.

Mycoplasma pneumoniae and Schistosoma mansoni co-infection in a young patient with extensive longitudinal acute transverse myelitis.

INTRODUCTION: Acute transverse myelitis is an uncommon inflammatory, intramedullary, disorder of the spinal cord. Spastic paraplegia, impaired sphincter functions, and sensory loss, with sensory level, are the clinical manifestations of this devastating disorder. The utilization of magnetic resonant imaging (MRI) contributes to the surge in the diagnosis of more ATM cases. Although the causes of ATM are numerous, both Mycoplasma pneumoniae and Schistosoma mansoni are uncommon causes and their co-existence in the same patient has not been reported before in Saudi Arabia. CASE: We report a 25-year-old ATM male patient presented with a history of sudden onset severe low back pain. Within four hours from the onset of the back pain, he became completely paraplegic with impaired functions of the bowel and urinary bladder sphincter. Furthermore, he lost all modalities of sensory functions in the lower limbs. His examination revealed spastic complete paraplegia with sensory level at T6. Clinical neurological examination revealed normal upper limbs and brain functions. The MRI of the cervico-dorsal spine showed extensive longitudinal hyperintense lesion extending from the upper cervical segments to the lower dorsal segments (extensive longitudinal transverse myelitis). A post-infectious immune-mediated predisposition was highly suspected due to the very high titers of anti-Mycoplasma pneumoniae IgM and IgG that were detected. The immunosuppressant therapy did not improve his paraplegia. A spinal cord biopsy revealed the presence of several Schistosoma mansoni ova surrounded by chronic inflammatory reactions and reactive gliosis. CONCLUSIONS: Both Mycoplasma pneumoniae and Schistosoma mansoni should be investigated in cases with extensive longitudinal ATM.

Curing somatisation-induced paraplegia with experimental dice-based affective modulation.

Following a minor meniscal injury to his right knee, a previously fit and well 58-year-old man developed profound somatisation leading to paraplegia. The patient developed a deep-seated belief that any exercise or walking would cause irreparable damage to his knee. Over the course of 2 years his, mobility reduced from active mountaineering to walking a short distance, and finally to paraplegia. Medical investigations were normal and organic causes were ruled out. Conventional therapy was exhausted, a number of medications were trialled over 5 years, including selective serotonin reuptake inhibitors (SSRIs) and antipsychotics without success. Eventually, with a combination of cognitive behavioural therapy, physiotherapy and a novel experimental therapy where the patient rolled dice and acted according to the roll results, the patient was able to literally and metaphorically get back on his feet.

Formation of a novel supraspinal-spinal connectome that relearns the same motor task after complete paralysis.

Having observed that electrical spinal cord stimulation and training enabled four patients with paraplegia with motor complete paralysis to regain voluntary leg movement, the underlying mechanisms involved in forming the newly established supraspinal-spinal functional connectivity have become of great interest. van den Brand et al. (Science 336: 1182-1185, 2012) subsequently, demonstrated the recovery, in response to spinal electro-neuromodulation and locomotor training, of voluntary stepping of the lower limbs in rats that received a lesion that is assumed to eliminate all long-descending cortical axons that project to lumbosacral segments. Here, we used a similar spinal lesion in rats to eliminate long-descending axons to determine whether a novel, trained motor behavior triggered by a unique auditory cue learned before a spinal lesion, could recover after the lesion. Hindlimb stepping recovered 1 mo after the spinal injury, but only after 2 mo, the novel and unique audio-triggered behavior was recovered, meaning that not only was a novel connectivity formed but also further evidence suggested that this highly unique behavioral response was independent of the recovery of the circuitry that generated stepping. The unique features of the newly formed supraspinal-spinal connections that mediated the recovery of the trained behavior is consistent with a guidance mechanism(s) that are highly use dependent.NEW & NOTEWORTHY Electrical spinal cord stimulation has enabled patients with paraplegia to regain voluntary leg movement, and so the underlying mechanisms involved in this recovery are of great interest. Here, we demonstrate in rodents the recovery of trained motor behavior after a spinal lesion. Rodents were trained to kick their right hindlimb in response to an auditory cue. This behavior recovered 2 mo after the paralyzing spinal cord injury but only with the assistance of electrical spinal cord stimulation.

Caffeine-induced hypokalemia: a case report.

BACKGROUND: With an increase in the global popularity of coffee, caffeine is one of the most consumed ingredients of modern times. However, the consumption of massive amounts of caffeine can lead to severe hypokalemia. CASE PRESENTATION: A 29-year-old man without a specific past medical history was admitted to our hospital with recurrent episodes of sudden and severe lower-extremity weakness. Laboratory tests revealed low serum potassium concentration (2.6-2.9 mmol/L) and low urine osmolality (100-130 mOsm/kgH2O) in three such prior episodes. Urinary potassium/urinary creatinine ratio was 12 and 16 mmol/gCr, respectively. The patient was not under medication with laxatives, diuretics, or herbal remedies. Through an in-depth interview, we found that the patient consumed large amounts of caffeine-containing beverages daily, which included > 15 cups of coffee, soda, and various kinds of tea. After the cessation of coffee intake and concomitant intravenous potassium replacement, the symptoms rapidly resolved, and the serum potassium level normalized. CONCLUSIONS: An increased intracellular shift of potassium and increased loss of potassium in urine due to the diuretic action have been suggested to be the causes of caffeine-induced hypokalemia. In cases of recurring hypokalemia of unknown cause, high caffeine intake should be considered.

Physiological responses to moderate intensity continuous and high-intensity interval exercise in persons with paraplegia.

STUDY DESIGN: Randomized crossover. OBJECTIVES: To test differences in the duration and magnitude of physiological response to isocaloric moderate intensity continuous (MICE) and high-intensity interval exercise (HIIE) sessions in persons with spinal cord injury (SCI). SETTING: Academic medical center in Miami, FL, USA. METHODS: Ten adult men (mean ± s.d.; 39 ± 10 year old) with chronic (13.2 ± 8.8 year) paraplegia (T2-T10) completed a graded exercise test. Then, in a randomized order, participants completed MICE and HIIE for a cost of 120 kcal. MICE was performed at 24.6% POpeak. During HIIE, exercise was completed in 2 min work and recovery phases at 70%:10% POpeak. RESULTS: MICE and HIIE were isocaloric (115.9 ± 21.8 and 116.6 ± 35.0 kcal, respectively; p = 0.903), but differed in duration (39.8 ± 4.6 vs 32.2 ± 6.2 min; p < 0.001) and average respiratory exchange ratio (RER; 0.90 ± 0.08 vs 1.01 ± 0.07; p = 0.002). During MICE, a workrate of 24.6 ± 6.7% POpeak elicited a V̇O2 of 53.1 ± 6.5% V̇O2peak (10.1 ± 2.2 ml kg-1 min-1). During HIIE, a workrate at 70% POpeak elicited 88.3 ± 6.7% V̇O2peak (16.9 ± 4.2 ml kg-1 min-1), and 29.4 ± 7.7% of the session was spent at or above 80% V̇O2peak. During HIIE working phase, RER declined from the first to last interval (1.08 ± 0.07 vs 0.98 ± 0.09; p < 0.001), reflecting an initially high but declining glycolytic rate. CONCLUSIONS: Compared with MICE, HIIE imposed a greater physiological stimulus while requiring less time to achieve a target caloric expenditure. Thus, exercise intensity might be an important consideration in the tailoring of exercise prescription to address the cardiometabolic comorbidities of SCI.

Development and deployment of an at-home strength and conditioning program to support a phase I trial in persons with chronic spinal cord injury.

STUDY DESIGN: Nonrandomized clinical trial (NCT02354625). OBJECTIVES: As a part of a Phase I clinical trial to assess the safety of autologous human Schwann cells (ahSC) in persons with chronic spinal cord injury (SCI), participants engaged in a multimodal conditioning program pre- and post-ahSC transplantation. The program included a home-based strength and endurance training program to prevent lack of fitness and posttransplantation detraining from confounding potential ahSC therapeutic effects. This paper describes development, deployment, outcomes, and challenges of the home-based training program. SETTING: University-based laboratory. METHODS: Development phase: two men with paraplegia completed an 8-week laboratory-based 'test' of the home-based program. Deployment phase: the first four (two males, two females) participant cohort of the ahSC trial completed the program at home for 12 weeks pre and 20 weeks post ahSC transplant. RESULTS: Development phase: both participants improved their peak aerobic capacity (VO2peak) (≥17%), peak power output (POpeak) (≥8%), and time to exhaustion (TTE) (≥7%). Deployment phase: pretransplant training minimally increased fitness in the two male participants (≥6% POpeak and ≥9% TTE). The two women had no POpeak changes and slight TTE changes (+2.6 and -1.2%, respectively.) All four participants detrained during the posttransplant recovery period. After posttransplant retraining, all four participants increased TTE (4-24%), three increased VO2peak (≥11%), and two increased POpeak (≥7%). CONCLUSIONS: Home-based strength and condition programs can be effective and successfully included in therapeutic SCI trials. However, development of these programs requires substantial content knowledge and experience.

Oxygen Uptake During Exoskeletal-Assisted Walking in Persons With Paraplegia.

OBJECTIVE: To determine the cardiometabolic demands associated with exoskeletal-assisted walking (EAW) in persons with paraplegia. This study will further examine if training in the device for 60 sessions modifies cost of transport (CT). DESIGN: Prospective cohort study. Measurements over the course of a 60-session training program, approximately 20 sessions apart. SETTING: James J. Peters Bronx Veterans Affairs Medical Center, Center for the Medical Consequences of Spinal Cord Injury Research Center. PARTICIPANTS: The participants' demographics (N=5) were 37-61 years old, body mass index (calculated as weight in kilograms divided by height in meters squared) of 22.7-28.6, level of injury from T1-T11, and 2-14 years since injury. INTERVENTIONS: Powered EAW. MAIN OUTCOME MEASURES: Oxygen consumption per unit time (V˙O2, mL/min/kg), velocity (m/min), cost of transport (V˙O2/velocity), and rating of perceived exertion (RPE). RESULTS: With training: EAW velocity significantly improved (Pre: 51±51m; 0.14±0.14m/s vs Post: 99±42m; 0.28±0.12m/s, P=.023), RPE significantly decreased (Pre: 13±6 vs Post: 7±4, P=.001), V˙O2 significantly improved (Pre: 9.76±1.23 mL/kg/m vs Post: 12.73±2.30 mL/kg/m, P=.04), and CT was reduced from the early to the later stages of training (3.66±5.2 vs 0.87±0.85 mL/kg/m). CONCLUSIONS: The current study suggests that EAW training improves oxygen uptake efficiency and walking velocities, with a lower perception of exertion.

Spinal cord stimulation and rehabilitation in an individual with chronic complete L1 paraplegia due to a conus medullaris injury: motor and functional outcomes at 18 months.

INTRODUCTION: Epidural electrical stimulation of the conus medullaris has helped facilitate native motor recovery in individuals with complete cervicothoracic spinal cord injuries (SCI). A theorized mechanism of clinical improvement includes supporting central pattern generators intrinsic to the conus medullaris. Because spinal cord stimulators (SCS) are approved for the treatment of neuropathic pain, we were able to test this experimental therapy in a subject with complete L1 paraplegia and neuropathic genital pain due to a traumatic conus injury. CASE PRESENTATION: An otherwise healthy 48-year-old male with chronic complete L1 paraplegia with no zones of partial preservation (ZPP) and intractable neuropathic genital pain presented to our group seeking nonmedical pain relief and any possible help with functional restoration. After extensive evaluation, discussion, and consent, we proceeded with SCS implantation at the conus and an intensive outpatient physical therapy regimen consistent with the recent SCI rehabilitation literature. DISCUSSION: Intraoperatively, no electromyography (EMG) could be elicited with epidural conus stimulation. At 18 months after implantation, his motor ZPPs had advanced from L1 to L5 on the left and from L1 to L3 on the right. Qualitative increases in lower extremity resting state EMG amplitudes were noted, although there was no consistent evidence of voluntary EMG or rhythmic locomotive leg movements. Three validated functional and quality of life (QoL) surveys demonstrated substantial improvements. The modest motor response compared to the literature suggests likely critical differences in the anatomy of such a low injury. However, the change in ZPPs and QoL suggest potential for neuroplasticity even in this patient population.

Unusual Manifestation of Spinal Epidural Arteriovenous Fistula as Sudden Paraplegia.

BACKGROUND: Spinal epidural arteriovenous fistulas (SEDAVFs) are a rare entity that cause gradual progression of neurological dysfunction. We present a case of SEDAVF with acute exacerbation of paraplegia that was successfully treated with emergency transarterial embolization. CASE DESCRIPTION: A 73-year-old man presented with low back pain, numbness in the lower extremities, and gait disturbance. T2-weighted magnetic resonance imaging revealed edema of the thoracolumbar spinal cord. Computed tomography angiography showed that the SEDAVF was fed by an expanded left L1 artery, epidural venous plexus at the left L1-2 intervertebral foramen, and intradural venous drainage. The patient suddenly developed severe paraplegia 2 days later. We performed emergency spinal angiography followed by transarterial embolization. The postoperative course was uneventful, and his preoperative symptoms improved. CONCLUSIONS: SEDAVFs may result in acute exacerbation that can be treated with an endovascular intervention-a rapid and effective means of obliterating shunts.

[Neurological Complications with Paraplegia as Main Manifestation after Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To investigate the cause, diagnosis and therapeutic method of the neurological complication with the main manifestation of paraplegia after the hematopoietic stem cell transplantation (HSCT). METHODS: The clinical features, the process of diagnosis and treatment and the prognosis follow-up of 9 cases, who received HSCT in our department during January 2014 and January 2017 and had the neurological complication with the main symptom of paraplegia after the transplantation, were summarized. RESULTS: The incidence rate of paraplegia was 2.96% (9/304). The median onset time was 245 days (50 days-772 days) after transplantation. The cause of paraplegia determined by examination was extramedullary recurrence of leukemia in 3 cases, cyclosporin neurotoxicity in 1 case, GBS in 1 case, CIDP in 2 cases and autoimmune myeleterosis in 2 cases. One patient abandoned the treatment. The rest 8 patients received empirical or targeted treatment. The median follow-up period was 11 months. There were 5 dead cases and 4 survival cases. CONCLUSION: Paraplegia is a serious post-HSCT complication. The cause of paraplegia should be determined as early as possible to perform targeted treatment. Empirical preemptive treatment should be given if necessary, so as to improve the survival rate and the quality of life of HSCT patients.

Timing and Modulation of Activity in the Lower Limb Muscles During Indoor Rowing: What Are the Key Muscles to Target in FES-Rowing Protocols?

The transcutaneous stimulation of lower limb muscles during indoor rowing (FES Rowing) has led to a new sport and recreation and significantly increased health benefits in paraplegia. Stimulation is often delivered to quadriceps and hamstrings; this muscle selection seems based on intuition and not biomechanics and is likely suboptimal. Here, we sample surface EMGs from 20 elite rowers to assess which, when, and how muscles are activated during indoor rowing. From EMG amplitude we specifically quantified the onset of activation and silencing, the duration of activity and how similarly soleus, gastrocnemius medialis, tibialis anterior, rectus femoris, vastus lateralis and medialis, semitendinosus, and biceps femoris muscles were activated between limbs. Current results revealed that the eight muscles tested were recruited during rowing, at different instants and for different durations. Rectus and biceps femoris were respectively active for the longest and briefest periods. Tibialis anterior was the only muscle recruited within the recovery phase. No side differences in the timing of muscle activity were observed. Regression analysis further revealed similar, bilateral modulation of activity. The relevance of these results in determining which muscles to target during FES Rowing is discussed. Here, we suggest a new strategy based on the stimulation of vasti and soleus during drive and of tibialis anterior during recovery.

Recommendations for standards of physiotherapy care following complete traumatic paraplegia in India.

STUDY DESIGN: Qualitative study. OBJECTIVES: To formulate recommendations for standards of physiotherapy care for people with complete traumatic paraplegia in India using a Delphi methodology. SETTING: India. METHODS: Twenty-three physiotherapy experts were invited to participate in an online consensus process. Fourteen (n = 14) of 23 physiotherapy experts from India accepted an invitation to participate in an online consensus development exercise (Response rate-60.86%). Four rounds of consensus meetings were conducted which involved posting the quotations from a previous study on expectations of people with paraplegia to obtain perceptions of physiotherapy experts in round 1, retrieving codes/code groups from round 1, posting these code groups in rounds 2 and 3 for experts' agreement/disagreement, the preparation of the draft of recommendations, and posting it in round 4 for experts' opinion. Data were analyzed using descriptive statistics and ATLASti software for qualitative data analysis. RESULT: Recommendations for physiotherapy care for persons with complete traumatic paraplegia in India are presented. CONCLUSIONS: Education to patients and/or caregivers regarding care post injury is one of the important recommendations by physiotherapy experts. It is emphasized that the subjective assessment of the patients, including their needs and preferences, is equally important as that of their objective assessment. Physiotherapy students and practicing physiotherapists must also enhance their knowledge to provide optimal physiotherapy care to people with paraplegia.

Spinal Cord Ischemia Rescue after Hybrid Total Arch Repair with Frozen Elephant Trunk: A Case Report.

Frozen elephant trunk repair is a technique described to simplify total arch repair for Stanford type A aortic dissection. Spinal cord ischemia is a devastating complication after frozen elephant trunk repair. In this report, we describe a case of spinal cord ischemia resulting in paralysis after frozen elephant trunk repair. Our spinal cord ischemia protocol was implemented and rescued patients from paraplegia. We report a dedicated spinal cord ischemia protocol that can rescue patients from paraplegia after hybrid arch repair with frozen elephant trunk.