Walking naturally after spinal cord injury using a brain-spine interface.

A spinal cord injury interrupts the communication between the brain and the region of the spinal cord that produces walking, leading to paralysis1,2. Here, we restored this communication with a digital bridge between the brain and spinal cord that enabled an individual with chronic tetraplegia to stand and walk naturally in community settings. This brain-spine interface (BSI) consists of fully implanted recording and stimulation systems that establish a direct link between cortical signals3 and the analogue modulation of epidural electrical stimulation targeting the spinal cord regions involved in the production of walking4-6. A highly reliable BSI is calibrated within a few minutes. This reliability has remained stable over one year, including during independent use at home. The participant reports that the BSI enables natural control over the movements of his legs to stand, walk, climb stairs and even traverse complex terrains. Moreover, neurorehabilitation supported by the BSI improved neurological recovery. The participant regained the ability to walk with crutches overground even when the BSI was switched off. This digital bridge establishes a framework to restore natural control of movement after paralysis.

Hypokalaemic quadriparesis in a patient with urinary diversion through Indiana pouch.

A man in his 20s, a patient with chronic kidney disease with a baseline estimated glomerular filtration rate of 33 mL/min/1.73 m2, who had an Indiana pouch continent urinary diversion procedure done at 6 years of age for bladder exstrophy, presented to the emergency room with sudden-onset progressive quadriparesis over 6 hours with power 1/5 in all the limbs with preserved reflexes. He was fully conscious and oriented, with stable vital signs. On evaluation, he had severe hypokalaemia and severe metabolic acidosis (both high anion gap and non-anion gap acidosis). Imaging studies showed bilateral gross hydroureteronephrosis, and renal and pouch calculi. Hypokalaemia was promptly treated with intravenous potassium chloride and acidosis with emergency haemodialysis. The patient had a complete motor recovery following intravenous potassium correction and was discharged with oral potassium and bicarbonate supplements. Here, the Indiana pouch, its metabolic and electrolyte complications, and its treatment are discussed.

Thoracoscopic intercostal to phrenic nerve transfer for diaphragmatic reanimation in a child with tetraplegia.

Context: To describe for the first time a novel technique of thoracoscopic intercostal nerve mobilization and intercostal to phrenic nerve transfer in the setting of tetraplegia with the goal of reanimating the diaphragm and decreasing ventilator dependence.Findings: A 5-year-old female on 24 h ventilator support secondary to traumatic tetraplegia was evaluated for possible phrenic nerve pacing. Left-sided phrenic nerve stimulation did not result in diaphragmatic contraction indicating a lower motor neuron injury. The patient underwent thoracoscopic mobilization of the left phrenic nerve and 10th intercostal nerve while positioned in the left lateral decubitus position using four 5 mm trocars. The mobilized intercostal nerve was transected close to its distal anterior termination and coapted without tension to the cut end of the terminal phrenic nerve using fibrin sealant. Lastly, phrenic nerve pacer leads and battery were implanted in the chest wall and connected to the electrode placed on the intercostal nerve. One year following the procedure, the patient was tolerating phrenic pacing during the day while requiring ventilation overnight. Currently, the patient is 2 years post-operative from this procedure and does not require ventilator support.Conclusion/clinical relevance: We have shown for the first time a novel approach of thoracoscopic nerve mobilization and phrenic to intercostal nerve transposition to be both safe and effective for restoring innervation of the diaphragm in a child. This minimally invasive procedure is recommended as the preferred approach to reanimate the diaphragm.

Selective neural electrical stimulation restores hand and forearm movements in individuals with complete tetraplegia.

BACKGROUND: We hypothesized that a selective neural electrical stimulation of radial and median nerves enables the activation of functional movements in the paralyzed hand of individuals with tetraplegia. Compared to previous approaches for which up to 12 muscles were targeted through individual muscular stimulations, we focused on minimizing the number of implanted electrodes however providing almost all the needed and useful hand movements for subjects with complete tetraplegia. METHODS: We performed acute experiments during scheduled surgeries of the upper limb with eligible subjects. We scanned a set of multicontact neural stimulation cuff electrode configurations, pre-computed through modeling simulations. We reported the obtained isolated and functional movements that were considered useful for the subject (different grasping movements). RESULTS: In eight subjects, we demonstrated that selective stimulation based on multicontact cuff electrodes and optimized current spreading over the active contacts provided isolated, compound, functional and strong movements; most importantly 3 out of 4 had isolated fingers or thumb flexion, one patient performed a Key Grip, another one the Power and Hook Grips, and the 2 last all the 3 Grips. Several configurations were needed to target different areas within the nerve to obtain all the envisioned movements. We further confirmed that the upper limb nerves have muscle specific fascicles, which makes it possible to activate isolated movements. CONCLUSIONS: The future goal is to provide patients with functional restoration of object grasping and releasing with a minimally invasive solution: only two cuff electrodes above the elbow. Ethics Committee / ANSM clearance prior to the beginning of the study (inclusion period 2016-2018): CPP Sud Méditerranée, #ID-RCB:2014-A01752-45, first acceptance 10th of February 2015, amended 12th of January 2016. TRIAL REGISTRATION: (www.clinicaltrials.gov): #NCT03721861, Retrospectively registered on 26th of October 2018.

Effects of MEG-based neurofeedback for hand rehabilitation after tetraplegia: preliminary findings in cortical modulations and grip strength.

OBJECTIVE: Neurofeedback (NF) trains people to volitionally modulate their cortical activity to affect a behavioral outcome. We evaluated the feasibility of using NF to improve hand function after chronic cervical-level spinal cord injury (SCI) using biologically-relevant visual feedback of motor-related brain activity and an intuitive control scheme. APPROACH: The NF system acquired magnetoencephalography (MEG) data in real-time to provide feedback of event-related desynchronization (ERD) measured over the sensorimotor cortex during attempted hand grasping. During brain control, stronger ERD resulting from attempted grasping drove the virtual hand towards a more closed grasp, while less ERD drove the hand more open. MAIN RESULTS: Eight individuals with partial or complete hand impairment due to chronic SCI controlled the NF to perform a grasping task that increased in difficulty as the participants achieved success. During their first NF session, participants achieved an average success rate of 63.7 ± 6.4% (chance level of 13.9%). After as few as one intervention session, four of the seven individuals evaluated for ERD changes had significantly strengthened ERD and three of the four participants with measurable grip strength prior to NF had increased grip strength. Interestingly, both individuals who participated in a longer-term study (i.e. >8 NF sessions) had improved grip strength and significantly strengthened ERD. SIGNIFICANCE: This study demonstrates that MEG-based NF training can change brain activity in individuals with hand impairment due to SCI and has the potential to induce acute changes in grip strength. Future studies will evaluate whether neuroplasticity induced with long term NF can improve hand function for those with moderate impairment.

Risk-benefit value of upper extremity function by an implanted electrical stimulation device targeting chronic cervical spinal cord injury.

Study design: A cross-sectional stated-preference survey using direct-assessment questions. Objective: To determine the relative value placed on different outcomes to be used in a pivotal trial for the upper extremity configuration of the Networked Neuroprosthesis (NNP) as well as the tolerance of the expected adverse event profile. Setting: Academic medical center in the United States. Methods: Distribution of an online survey to adults living with tetraplegia; extent of agreement with each question/statement was obtaining using a 1-7 Likert scale. Results: There were 8 statements about potential benefits in arm/hand function; for all statements, more than 70% of participants rated the functions as "1-very important" to regain. There were variable degrees of concern related to risks that could occur during the 30-day post-surgical period and increasing degrees of concern related to risks that could occur in the first 5 years, potentially due to the device, based on the increasing degree of invasiveness of the intervention required to address the event. When analysing the results based on all degrees of interest, more than 64% of responders were interested in getting the NNP with a success rate threshold as low as 50% regardless of time post-injury. Chi-squared analyses revealed some associations between responses and sex, injury level, and injury duration; however, none of these were statistically significant upon post-hoc analysis. Conclusion: Data here indicate that people with tetraplegia are highly interested in a range of arm/hand functions and are tolerant of expected risks that may be associated with implanted neuroprosthetics. Sponsorship: The Institute for Functional Restoration funded this project through a sub-contract to K.D. Anderson from a larger Special Projects Award (grant number FP0020773) from the Craig H. Neilsen Foundation.

Restoration of hand function with long-term paired associative stimulation after chronic incomplete tetraplegia: a case study.

Introduction: This case study explores the gains in hand function in an individual with a chronic spinal cord injury (SCI). The intervention was long-term paired associative simulation (PAS). We aimed to provide PAS until full recovery of hand muscle strength occurred, or until improvements ceased. Case presentation: A 46-year-old man with traumatic C7 AIS B tetraplegia was administered PAS three times per week. After 24 weeks, PAS was combined with concomitant motor training of the remaining weak hand muscles. Outcome measures included the manual muscle test (MMT), motor-evoked potentials (MEPs), F-responses, hand functional tests, and the spinal cord independence measure (SCIM). Discussion: After 47 weeks of PAS the subject had improved self-care and indoor mobility and was able to perform complex motor tasks (SCIM score improved from 40 to 56). His left hand regained maximum MMT score (total 75; increase of score from baseline condition 19); the effect remained stable in the 32-week follow up. In the right-hand muscles, MMT scores of 4-5 were observed in follow up (total 71; increase from baseline 48). Improved values were also observed in other outcomes. This is the first demonstration of long-term PAS restoring muscle strength corresponding to MMT scores of 4-5 in an individual with chronic SCI. The effect persisted for several months, indicating that PAS induces stable plastic changes in the corticospinal pathway.

Case Study: Cognitive Restructuring Hypnosis for Chronic Pain in a Quadriplegic Patient.

This case study reports on a 28-year-old male with spinal cord injury (SCI), quadriplegia, and chronic pain with neuropathic characteristics. The treatment had to be adapted to address the patient's needs, as he was on a respirator and paralyzed from the chin down. The intervention consisted of eight 90-minute sessions. The first four sessions were based on a standardized hypnotic cognitive therapy protocol developed for a randomized controlled trial (RCT). The sessions included training in cognitive restructuring skills and a hypnosis session with suggestions that was audiorecorded. Instructions to practice at home, both with the recording and by using self-hypnosis, were provided as well. Most of the outcome domains assessed (i.e., pain intensity, pain interference, sleep quality) showed clinically meaningful improvements that were maintained (or increased) at one-year follow-up. The patient reported that he was still using self-hypnosis at one-year follow-up. His subjective impression of change was positive and he did not report any negative side effects. Results show that the hypnotic cognitive therapy protocol used is a promising intervention that can benefit individuals with SCI presenting with complex symptomatology. Such therapy helps patients by teaching them effective coping strategies that they can use on their own to manage pain and its effects. In addition, it is important to note that this therapy provided benefits to someone who had not experienced any benefits from numerous medications he had tried before treatment. Therefore, the findings support continued efforts to make this treatment more accessible to patients who could benefit from this approach.

Is neck massage safe? A rare case of tetraplegia and spinal shock after neck manipulation.

Neck manipulation is associated with spinal cord injury. However, occurrence of such cases is infrequent. This article presents a 33-year-old gentleman who sustained acute tetraplegia after neck manipulation. The aim of this case report is to create awareness that vigorous neck manipulation could cause injury to the spinal cord.

Quadriparesis Caused by Lead Poisoning Nine Years After a Gunshot Wound With Retained Bullet Fragments: A Case Report.

Lead toxicity in adults is characterized by nonspecific symptoms of abdominal pain, vomiting, constipation, fatigue, and weight loss. We present a case of severe lead toxicity that developed subacutely, causing quadriparesis 9 years after a gunshot wound with retained bullet fragments. The onset of symptoms may have been related to the development of a pseudocyst. The long interval between the gunshot wound and the onset of symptoms contributed to a delay in suspecting that the retained bullet was a source of lead toxicity. The patient's symptoms gradually improved after chelation therapy, removal of the bullet fragment, and an extended program of acute inpatient rehabilitation. LEVEL OF EVIDENCE: V.

An Acute Cervical Subdural Hematoma as the Complication of Acupuncture: Case Report and Literature Review.

BACKGROUND: Several injuries in the cervical region as complications of acupuncture have been previously reported in the literature, including cord and medulla oblongata injuries, subdural empyema, and cervical hematoma. Spinal cord subdural hematoma is a rare condition mainly associated with coagulopathy, trauma, and iatrogenic procedures. We herein report an acute cervical subdural hematoma after cervical acupuncture for neck and shoulder pain. CASE DESCRIPTION: A 74-year-old woman presented with progressive quadriparesis and sensory deficit after receiving acupuncture in the neck and shoulder. Magnetic resonance imaging of the cervical spine showed a subdural lesion that was a hyperintense mass in the T1-weighted and hypointense in T2-weighted images at the C4-C6 level, which proved to be an early subacute subdural hematoma. After surgical evacuation of the hematoma, the patient had significant neurologic improvement. CONCLUSIONS: Although rare, cervical spinal cord hematomas are disastrous complications of cervical acupuncture. These procedures should be performed under direct observation of trained physicians with appropriate knowledge of cervical anatomy to avoid these complications.

Role of Functional Electrical Stimulation in Tetraplegia Hand Surgery.

The use of functional electrical stimulation (FES) to improve upper limb function is an established method in the rehabilitation of persons with tetraplegia after spinal cord injury. Surgical reconstruction is another well-established yet underused technique to improve the performance of the upper extremities. Hand surgery plays an essential role in restoring hand function, mobility, and quality of life in the tetraplegic population. The knowledge about the effects of FES on a structural and functional level is fundamental for understanding how and when FES can be used best to support the effect of hand surgery, both pre- and postoperatively. In this article we discuss principles of FES and how FES improves functional outcome after surgical reconstruction. The reported results are based on preliminary clinical observations.

Engaging Cervical Spinal Cord Networks to Reenable Volitional Control of Hand Function in Tetraplegic Patients.

BACKGROUND: Paralysis of the upper limbs from spinal cord injury results in an enormous loss of independence in an individual's daily life. Meaningful improvement in hand function is rare after 1 year of tetraparesis. Therapeutic developments that result in even modest gains in hand volitional function will significantly affect the quality of life for patients afflicted with high cervical injury. The ability to neuromodulate the lumbosacral spinal circuitry via epidural stimulation in regaining postural function and volitional control of the legs has been recently shown. A key question is whether a similar neuromodulatory strategy can be used to improve volitional motor control of the upper limbs, that is, performance of motor tasks considered to be less "automatic" than posture and locomotion. In this study, the effects of cervical epidural stimulation on hand function are characterized in subjects with chronic cervical cord injury. OBJECTIVE: Herein we show that epidural stimulation can be applied to the chronic injured human cervical spinal cord to promote volitional hand function. METHODS AND RESULTS: Two subjects implanted with a cervical epidural electrode array demonstrated improved hand strength (approximately 3-fold) and volitional hand control in the presence of epidural stimulation. CONCLUSIONS: The present data are sufficient to suggest that hand motor function in individuals with chronic tetraplegia can be improved with cervical cord neuromodulation and thus should be comprehensively explored as a possible clinical intervention.

A Case Report of Locked-in Syndrome Due to Bilateral Vertebral Artery Dissection After Cervical Spine Manipulation Treated by Arterial Embolectomy.

Cervical spine manipulation (CSM) is a commonly spinal manipulative therapies for the relief of cervical spine-related conditions worldwide, but its use remains controversial. CSM may carry the potential for serious neurovascular complications, primarily due to vertebral artery dissection (VAD) and subsequent vertebrobasilar stroke. Here, we reported a rare case of locked-in syndrome (LIS) due to bilaterial VAD after CSM treated by arterial embolectomy.A 36-year-old right-handed man was admitted to our hospital with numbness and weakness of limbs after treating with CSM for neck for half an hour. Gradually, although the patient remained conscious, he could not speak but could communicate with the surrounding by blinking or moving his eyes, and turned to complete quadriplegia, complete facial and bulbar palsy, dyspnea at 4 hours after admission. He was diagnosed with LIS. Then, the patient was received cervical and brain computed tomography angiography that showed bilateral VAD. Aortocranial digital subtraction angiography showed vertebrobasilar thrombosis, blocking left vertebral artery, and stenosis of right vertebral artery. The patient was treated by using emergency arterial embolectomy and followed by antiplatelet therapy and supportive therapy in the intensive care unit and a general ward. Twenty-seven days later, the patient's physical function gradually improved and discharged but still left neurological deficit with muscle strength grade 3/5 and hyperreflexia of limbs.Our findings suggested that CSM might have potential severe side-effect like LIS due to bilaterial VAD, and arterial embolectomy is an important treatment choice. The practitioner must be aware of this complication and should give the patients informed consent to CSM, although not all stroke cases temporally related to SCM have pre-existing craniocervical artery dissection.

Sacral neuromodulation: No more skiing?

Patients with spinal cord injury (SCI) commonly suffer from neurogenic lower urinary tract dysfunction (NLUTD). Sacral neuromodulation (SNM) offers an alternative in the treatment of detrusor overactivity in patients with NLUTD. We report the cases of three patients with NLUTD due to SCI who received SNM. Due to treatment success, all patients could resume skiing. All suffered from skiing accidents, leading to a decreased effectiveness of SNM. Subsequent evaluation revealed a defect of the impulse generator (IPG) and/or dislocation of the electrodes. Reprogramming or replacement of the IPG or the electrodes resulted in restoration of SNM function. Trauma due to skiing is a potential risk factor for the integrity of SNM. Patients with SNM should be informed about the potential risk of SNM damage by falls and accidents.

Acute-onset paralysis in a patient of rheumatoid arthritis.

Renal tubular acidosis (RTA) is a disorder of renal acidification characterized by inability to acidify urine to pH < 5.5 despite the presence of severe systemic metabolic acidosis and hypokalemia. Hypokalemia leads to acute-onset paralysis and may be a presenting manifestation of RTA. Its association with various autoimmune disease has been reported previously in published reports, but has not been much emphasized. We, hereby, report a case of RTA that presented during the flare of rheumatoid arthritis (RA). A 42-year-old female, a known case of RA for 5 years, presented with persistent joint pain for 1 week and acute-onset quadriparesis for 3 days. Primary investigations revealed hypokalemia with metabolic acidosis. She was managed conservatively with potassium supplements and bicarbonate supplements along with steroids and disease-modifying anti-rheumatic drugs. Such a presentation of renal tubular acidosis in a patient during the flare of rheumatoid arthritis is distinctly rare and previously unreported in published studies.

Complicated fecal microbiota transplantation in a tetraplegic patient with severe Clostridium difficile infection.

A 65-year-old male suffering from acute spinal cord injury leading to incomplete tetraplegia presented with severe recurrent Clostridium difficile (C. difficile) infection subsequent to antibiotic treatment for pneumonia. After a history of ineffective antimicrobial therapies, including metronidazole, vancomycin, fidaxomicin, rifaximin and tigecycline, leading to several relapses, the patient underwent colonoscopic fecal microbiota transplantation from his healthy son. Four days subsequent to the procedure, the patient showed a systemic inflammation response syndrome. Without detecting an infectious cause, the patient received antimicrobial treatment, including tigecycline, metronidazole, vancomycin via polyethylene glycol and an additional enema for a period of seven days, leading to a prompt recovery and no reported C. difficile infection relapse during a 12 wk follow up.

Circadian rhythms of hemostatic factors in tetraplegia: a double-blind, randomized, placebo-controlled cross-over study of melatonin.

STUDY DESIGN: This is a double-blind, randomized, placebo-controlled cross-over study of melatonin in complete tetraplegia. OBJECTIVES: Tetraplegic patients have an increased risk of venous thrombosis despite prophylaxis, blunted variations in melatonin and altered circadian variation of several hemostatic markers. To examine whether melatonin could modify the regulation of hemostasis, we measured plasma melatonin and several markers of hemostasis in tetraplegic subjects with or without melatonin supplement. SETTING: The study was conducted in the Section for Spinal Cord Injury, Sunnaas Hospital, Nesoddtangen, Norway. METHODS: Six subjects with long-standing complete tetraplegia were included in this cross-over study with 2 mg of melatonin or placebo given 4 days before sampling. We also included six able-bodied men without any intervention. Plasma samples were then collected frequently during a 24-h awake/sleep cycle. The plasma concentrations of melatonin and the various markers were analyzed using linear mixed models. RESULTS: The 24-h profiles of prothrombin fragment 1+2 and von Willebrand factor, but not D-dimer, activated FVII, tissue factor pathway inhibitor and plasminogen activator inhibitor type 1, differed (P<0.05) between tetraplegic patients and able-bodied subjects. The absolute plasma concentration of activated FVII was higher (P<0.05) among the able-bodied compared with the tetraplegic groups. Supplementation of melatonin had no impact on these findings. CONCLUSIONS: We found differences in circadian variation of several hemostatic markers between able-bodied and tetraplegics. These differences were apparently unrelated to fluctuations in the melatonin concentrations, suggesting little or no role of melatonin in the regulation of hemostasis in tetraplegia. SPONSORSHIP: Financial support was provided from the Throne Holst Foundation.

Effect of active pulmonary rehabilitation on pulmonary function in patients with brain lesion.

BACKGROUND: The patients with brain lesion have a high risk of pulmonary complication due to restrictive pulmonary impairment. OBJECTIVE: To investigate the effectiveness of active pulmonary rehabilitation on pulmonary functional improvement in these patients. METHODS: Twnety-two patients of hemiplegia or quadriplegia with brain lesion were recruited who had restrictive pulmonary impairment. The patients were randomly assigned to an experimental group that receive active pulmonary rehabilitation training and a control group without it. The active pulmonary rehabilitation training is composed of air-stacking exercise by ambu-bagging and functional electrical stimulation (FES) on phrenic nerve and abdominal muscle. We examined respiration function test of all patients composed of peak cough flow (PCF), pulmonary function test (PFT), diaphragmatic motion evaluation and oxygen saturation (SaO2) at the beginning and 4 weeks after treatment. RESULTS: There was no significant difference in pulmonary function between experimental group and control group at the beginning. After 4 weeks treatment, FVC and FEV1 of PFT, PCF, diaphragmatic motion, SaO2 have significantly improved (p < 0.05) in experimental group, but no significant changes were detected in control group. CONCLUSIONS: It is suggested that active pulmonary rehabilitation with air-stacking exercise and FES would be useful to improve pulmonary function in patients with brain lesion.

Bone mass in individuals with chronic spinal cord injury: associations with activity-based therapy, neurologic and functional status, a retrospective study.

OBJECTIVE: To describe the prevalence of osteoporosis and its association with functional electrical stimulation (FES) use in individuals with spinal cord injury (SCI)-related paralysis. DESIGN: Retrospective cross-sectional evaluation. SETTING: Clinic. PARTICIPANTS: Consecutive persons with SCI (N=364; 115 women, 249 men) aged between 18 and 80 years who underwent dual-energy x-ray absorptiometry (DXA) examinations. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Prevalence of osteoporosis defined as DXA T score ≤-2.5. RESULTS: The prevalence of osteoporosis was 34.9% (n=127). Use of FES was associated with 31.2% prevalence of osteoporosis compared with 39.5% among persons not using FES. In multivariate adjusted logistic regression analysis, FES use was associated with 42% decreased odds of osteoporosis after adjusting for sex, age, body mass index, type and duration of injury, Lower Extremity Motor Scores, ambulation, previous bone fractures, and use of calcium, vitamin D, and anticonvulsant; (adjusted odds ratio [OR]=.58; 95% confidence interval [CI], .35-.99; P=.039). Duration of injury >1 year was associated with a 3-fold increase in odds of osteoporosis compared with individuals with injury <1 year; (adjusted OR=3.02; 95% CI, 1.60-5.68; P=.001). CONCLUSIONS: FES cycling ergometry may be associated with a decreased loss of bone mass after paralysis. Further prospective examination of the role of FES in preserving bone mass will improve our understanding of this association.