Supraspinal nociceptive networks in neuropathic pain after spinal cord injury.

Neuropathic pain following spinal cord injury involves plastic changes along the whole neuroaxis. Current neuroimaging studies have identified grey matter volume (GMV) and resting-state functional connectivity changes of pain processing regions related to neuropathic pain intensity in spinal cord injury subjects. However, the relationship between the underlying neural processes and pain extent, a complementary characteristic of neuropathic pain, is unknown. We therefore aimed to reveal the neural markers of widespread neuropathic pain in spinal cord injury subjects and hypothesized that those with greater pain extent will show higher GMV and stronger connectivity within pain related regions. Thus, 29 chronic paraplegic subjects and 25 healthy controls underwent clinical and electrophysiological examinations combined with neuroimaging. Paraplegics were demarcated based on neuropathic pain and were thoroughly matched demographically. Our findings indicate that (a) spinal cord injury subjects with neuropathic pain display stronger connectivity between prefrontal cortices and regions involved with sensory integration and multimodal processing, (b) greater neuropathic pain extent, is associated with stronger connectivity between the posterior insular cortex and thalamic sub-regions which partake in the lateral pain system and (c) greater intensity of neuropathic pain is related to stronger connectivity of regions involved with multimodal integration and the affective-motivational component of pain. Overall, this study provides neuroimaging evidence that the pain phenotype of spinal cord injury subjects is related to the underlying function of their resting brain.

Update from TASCI, a Nationwide, Randomized, Sham-controlled, Double-blind Clinical Trial on Transcutaneous Tibial Nerve Stimulation in Patients with Acute Spinal Cord Injury to Prevent Neurogenic Detrusor Overactivity.

Transcutaneous tibial nerve stimulation has the potential to revolutionize the management of lower urinary tract dysfunction in patients with acute spinal cord injury. TASCI is a nationwide randomized, sham-controlled, double-blind clinical trial for which the preparatory phase has been successfully completed.

MR Spectroscopy of the Cervical Spinal Cord in Chronic Spinal Cord Injury.

Purpose To investigate metabolic changes in chronic spinal cord injury (SCI) by applying MR spectroscopy in the cervical spinal cord. Materials and Methods Single-voxel short-echo spectroscopic data in study participants with chronic SCI and healthy control subjects were prospectively acquired in the cervical spinal cord at C2 above the level of injury between March 2016 and January 2017 and were compared between groups. Concentrations of total N-acetylaspartate (tNAA), myo-inositol (mI), total choline-containing compounds (tCho), creatine, and glutamine and glutamate complex were estimated from the acquired spectra. Participants were assessed with a comprehensive clinical evaluation investigating sensory and motor deficits. Correlation analysis was applied to investigate relationships between observed metabolic differences, lesion severity, and clinical outcome. Results There were 18 male study participants with chronic SCI (median age, 51 years; range, 30-68 years) and 11 male healthy control subjects (median age, 45 years; range, 30-67 years). At cervical level C2, tNAA/mI and tCho/mI ratios were lower in participants with SCI (tNAA/mI: -26%, P = .003; tCho/mI: -18%; P = .04) than in healthy control subjects. The magnitude of difference was greater with the severity of cord atrophy (tNAA/mI: R2 = 0.44, P = .003; tCho/mI: R2 = 0.166, P = .09). Smaller tissue bridges at the lesion site correlated with lower ratios of tNAA/mI (R2 = 0.69, P = .006) and tCho/mI (R2 = 0.51, P = .03) at the C2 level. Lower tNAA/mI and tCho/mI ratios were associated with worse sensory and motor outcomes (P < .05). Conclusion Supralesional metabolic alterations are observed in chronic spinal cord injury, likely reflecting neurodegeneration, demyelination, and astrocytic gliosis in the injured cervical cord. Lesion severity and greater clinical impairment are both linked to the biochemical changes in the atrophied cervical cord after spinal cord injury. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Lin in this issue.

Quantitative MRI of rostral spinal cord and brain regions is predictive of functional recovery in acute spinal cord injury.

Objective: To reveal the immediate extent of trauma-induced neurodegenerative changes rostral to the level of lesion and determine the predictive clinical value of quantitative MRI (qMRI) following acute spinal cord injury (SCI). Methods: Twenty-four acute SCI patients and 23 healthy controls underwent a high-resolution T1-weighted protocol. Eighteen of those patients and 20 of controls additionally underwent a multi-parameter mapping (MPM) MRI protocol sensitive to the content of tissue structure, including myelin and iron. Patients were examined clinically at baseline, 2, 6, 12, and 24 months post-SCI. We assessed volume and microstructural changes in the spinal cord and brain using T1-weighted MRI, magnetization transfer (MT), longitudinal relaxation rate (R1), and effective transverse relaxation rate (R2*) maps. Regression analysis determined associations between acute qMRI parameters and recovery. Results: At baseline, cord area and its anterior-posterior width were decreased in patients, whereas MT, R1, and R2* parameters remained unchanged in the cord. Within the cerebellum, volume decrease was paralleled by increases of MT and R2* parameters. Early grey matter changes were observed within the primary motor cortex and limbic system. Importantly, early volume and microstructural changes of the cord and cerebellum predicted functional recovery following injury. Conclusions: Neurodegenerative changes rostral to the level of lesion occur early in SCI, with varying temporal and spatial dynamics. Early qMRI markers of spinal cord and cerebellum are predictive of functional recovery. These neuroimaging biomarkers may supplement clinical assessments and provide insights into the potential of therapeutic interventions to enhance neural plasticity.

Early urological care of patients with spinal cord injury.

PURPOSE: After spinal cord injury (SCI), the initial goals of urological management include maintaining safe storage of urine with efficient bladder emptying, maximising urinary continence, and minimising the risk of urological complications. METHODS: This review was performed according to the methodology recommended by the Joint SIU-ICUD International Consultation. Embase and Medline databases were used to identify literature relevant to the early urological care of SCI patients. Recommendations were developed by consensus and graded using a modified Oxford system which identifies level of evidence (LOE) and grade of recommendation (GOR). RESULTS: Clinicians must ensure appropriate bladder emptying immediately after SCI (LOE 3, GOR A) and perform the initial neuro-urological assessment within 3 months after injury (LOE 3, GOR A), including history, validated questionnaires, bladder diary, physical examination, measurement of renal function, and urinary tract imaging (LOE 4, GOR B). Urodynamics, if available video-urodynamics, must be performed to detect and specify lower urinary tract dysfunction (LOE 1, GOR A). Spontaneous voiding and/or intermittent catheterization must be considered in appropriate patients once they are medically stable (LOE 3, GOR A). Antimuscarinics are the first-line and intradetrusor botulinum toxin A injections are the second-line treatment for neurogenic detrusor overactivity (LOE 1, GOR A). Irreversible surgical interventions should be delayed until the second year after injury due to the potential for neurological recovery (LOE 4, GOR B). CONCLUSIONS: Careful clinical assessment and pertinent urological testing including urodynamic investigation are necessary for appropriate counselling and treatment of new SCI patients.

Traumatic spinal cord injury.

Traumatic spinal cord injury (SCI) has devastating consequences for the physical, social and vocational well-being of patients. The demographic of SCIs is shifting such that an increasing proportion of older individuals are being affected. Pathophysiologically, the initial mechanical trauma (the primary injury) permeabilizes neurons and glia and initiates a secondary injury cascade that leads to progressive cell death and spinal cord damage over the subsequent weeks. Over time, the lesion remodels and is composed of cystic cavitations and a glial scar, both of which potently inhibit regeneration. Several animal models and complementary behavioural tests of SCI have been developed to mimic this pathological process and form the basis for the development of preclinical and translational neuroprotective and neuroregenerative strategies. Diagnosis requires a thorough patient history, standardized neurological physical examination and radiographic imaging of the spinal cord. Following diagnosis, several interventions need to be rapidly applied, including haemodynamic monitoring in the intensive care unit, early surgical decompression, blood pressure augmentation and, potentially, the administration of methylprednisolone. Managing the complications of SCI, such as bowel and bladder dysfunction, the formation of pressure sores and infections, is key to address all facets of the patient's injury experience.

Neuroprosthetic technologies to augment the impact of neurorehabilitation after spinal cord injury.

Spinal cord injury leads to a range of disabilities, including limitations in locomotor activity, that seriously diminish the patients' autonomy and quality of life. Electrochemical neuromodulation therapies, robot-assisted rehabilitation and willpower-based training paradigms restored supraspinal control of locomotion in rodent models of severe spinal cord injury. This treatment promoted extensive and ubiquitous remodeling of spared circuits and residual neural pathways. In four chronic paraplegic individuals, electrical neuromodulation of the spinal cord resulted in the immediate recovery of voluntary leg movements, suggesting that the therapeutic concepts developed in rodent models may also apply to humans. Here, we briefly review previous work, summarize current developments, and highlight impediments to translate these interventions into medical practice to improve functional recovery of spinal-cord-injured individuals.

Effectiveness of High-Frequency Electrical Stimulation Following Sensitization With Capsaicin.

UNLABELLED: Although nonnoxious, high-frequency electrical stimulation applied segmentally (ie, conventional transcutaneous electrical nerve stimulation [TENS]) has been proposed to modulate pain, the mechanisms underlying analgesia remain poorly understood. To further elucidate how TENS modulates pain, we examined evoked responses to noxious thermal stimuli after the induction of sensitization using capsaicin in healthy volunteers. We hypothesized that sensitization caused by capsaicin application would unmask TENS analgesia, which could not be detected in the absence of sensitization. Forty-nine healthy subjects took part in a series of experiments. The experiments comprised the application of topical capsaicin (.075%) on the left hand in the C6 dermatome, varying the location of TENS (segmental, left C6 dermatome, vs extrasegmental, right shoulder), and assessing rating of perception (numeric rating scale: 0-10) and evoked potentials to noxious contact heat stimuli. The extrasegmental site was included as a control condition because previous studies indicate no analgesic effect to remote conventional TENS. Conventional TENS had no significant effect on rating or sensory evoked potentials in subjects untreated with capsaicin. However, segmental TENS applied in conjunction with capsaicin significantly reduced sensation to noxious thermal stimuli following a 60-minute period of sensitization. PERSPECTIVE: The study indicates that sensitization with capsaicin unmasks the analgesic effect of conventional TENS on perception of noxious contact heat stimuli. Our findings indicate that TENS may be interacting segmentally to modulate distinct aspects of sensitization, which in turn results in analgesia to thermal stimulation.

A case of undiagnosed tethered cord syndrome aggravated by transurethral prostate resection.

BACKGROUND: A 68-year-old man presented with a history of significant urinary urge incontinence, pollakiuria, and weak bladder sensation. He also reported mild fecal incontinence and a hypotrophic and slightly weaker left leg. At 63 years of age he had presented to a urologist for treatment of irritative lower urinary tract symptoms and incontinence. A transurethral resection of the prostate had been performed. After the operation, the symptoms had persisted and the incontinence seriously worsened. INVESTIGATIONS: Clinical neurologic examination, videourodynamic examination, neurophysiologic examination, and MRI of the spinal cord. DIAGNOSIS: Neurogenic bladder dysfunction caused by adult tethered cord syndrome with myelon up to S2 level, spina bifida occulta, and lipoma infiltrating the conus medullaris. MANAGEMENT: Conservative anticholinergic treatment failed, and injection of botulinum-A toxin is planned.

What disconnection tells about motor imagery: evidence from paraplegic patients.

Brain activation during motor imagery has been the subject of a large number of studies in healthy subjects, leading to divergent interpretations with respect to the role of descending pathways and kinesthetic feedback on the mental rehearsal of movements. We investigated patients with complete spinal cord injury (SCI) to find out how the complete disruption of motor efferents and sensory afferents influences brain activation during motor imagery of the disconnected feet. Eight SCI patients underwent behavioral assessment and functional magnetic resonance imaging. When compared to a healthy population, stronger activity was detected in primary and all non-primary motor cortical areas and subcortical regions. In paraplegic patients the primary motor cortex was consistently activated, even to the same degree as during movement execution in the controls. Motor imagery in SCI patients activated in parallel both the motor execution and motor imagery networks of healthy subjects. In paraplegics the extent of activation in the primary motor cortex and in mesial non-primary motor areas was significantly correlated with the vividness of movement imagery, as assessed by an interview. The present findings provide new insights on the neuroanatomy of motor imagery and the possible role of kinesthetic feedback in the suppression of cortical motor output required during covert movements.

Urethral evoked sympathetic skin responses and viscerosensory evoked potentials as diagnostic tools to evaluate urogenital autonomic afferent innervation in spinal cord injured patients.

PURPOSE: In most spinal cord injured (SCI) patients the objective assessment of afferent neuronal pathways from the lower urinary tract and the recording of a disturbed urethral sensation and/or desire to void are still difficult. Viscerosensory evoked potentials (VSEPs) might be helpful, but they remain technically difficult to obtain and interpretation is delicate. As a new approach, sympathetic skin response (SSR) of the hand and foot were recorded after electrical stimulation of the posterior urethral mucosa. This technique should allow assessment of the integrity or deterioration of the autonomic afferent pathway. MATERIALS AND METHODS: A total of 20 males and 8 females with SCI somatosensory incomplete 15, somatosensory complete 13 and 6 healthy male volunteers were prospectively examined. During urodynamic examination electrical stimulation (single square pulses of 0.2 ms, 2 to 3-fold sensory threshold, 60 mA in complete SCI patients) of the posterior urethra/bladder neck was performed using a bipolar electrode inserted into a microtip pressure catheter. SSR recordings of the right palm and sole were simultaneously taken using surface electrodes and were analyzed by an electromyography unit. Patient reports on evoked urethral sensations at individual sensory thresholds were simultaneously noted. Additionally, well-known electrophysiological measurements such as pudendal sensory evoked potential and urethral VSEP were recorded to check clinical assessed somatosensory and viscerosensory status, and to compare SSR results with these conventional methods. RESULTS: Electrical stimulation of the posterior urethra evoked clear urethral sensation and SSRs in normal subjects. In 14 of 15 sensory incomplete SCI patients with disturbed urethral sensation SSRs could be recorded as well. Electrically evoked urethral sensations resembled the subjective desire to void at full bladder reported by controls and patients. In 13 sensory complete SCI patients with loss of any urethral sensation SSRs could not be recorded even at maximal electrical stimulation strength. All subjects with electrically induced urethral sensation had positive evoked (supralesional) SSRs of the hand. However, none of the patients with absent urethral sensation presented SSRs. Simultaneously recorded VSEPs could not be recorded clearly in 5 patients and 2 control subjects, whereas SSRs delivered clear results in all controls and patients, matching their reports. CONCLUSIONS: SSR recordings above a spinal lesion level after urethral electrostimulation might provide a useful and technically simple objective diagnostic tool to assess integrity of autonomic (visceral) afferent nerves from the lower urinary tract. Somatosensory deficits are not always paralleled by viscerosensory loss and vice versa. In this study SSRs were superior to VSEPs, the latter being more difficult to record. The subjective sensations reported by subjects during stimulation could be confirmed in an objective way in 100% of cases by positive/negative SSR findings.