Acute Spinal Cord Injury: Correlations and Causal Relations Between Intraspinal Pressure, Spinal Cord Perfusion Pressure, Lactate-to-Pyruvate Ratio, and Limb Power.

BACKGROUND/OBJECTIVE: We have recently developed monitoring from the injury site in patients with acute, severe traumatic spinal cord injuries to facilitate their management in the intensive care unit. This is analogous to monitoring from the brain in patients with traumatic brain injuries. This study aims to determine whether, after traumatic spinal cord injury, fluctuations in the monitored physiological, and metabolic parameters at the injury site are causally linked to changes in limb power. METHODS: This is an observational study of a cohort of adult patients with motor-incomplete spinal cord injuries, i.e., grade C American spinal injuries association Impairment Scale. A pressure probe and a microdialysis catheter were placed intradurally at the injury site. For up to a week after surgery, we monitored limb power, intraspinal pressure, spinal cord perfusion pressure, and tissue lactate-to-pyruvate ratio. We established correlations between these variables and performed Granger causality analysis. RESULTS: Nineteen patients, aged 22-70 years, were recruited. Motor score versus intraspinal pressure had exponential decay relation (intraspinal pressure rise to 20 mmHg was associated with drop of 11 motor points, but little drop in motor points as intraspinal pressure rose further, R2 = 0.98). Motor score versus spinal cord perfusion pressure (up to 110 mmHg) had linear relation (1.4 motor point rise/10 mmHg rise in spinal cord perfusion pressure, R2 = 0.96). Motor score versus lactate-to-pyruvate ratio (greater than 20) also had linear relation (0.8 motor score drop/10-point rise in lactate-to-pyruvate ratio, R2 = 0.92). Increased intraspinal pressure Granger-caused increase in lactate-to-pyruvate ratio, decrease in spinal cord perfusion, and decrease in motor score. Increased spinal cord perfusion Granger-caused decrease in lactate-to-pyruvate ratio and increase in motor score. Increased lactate-to-pyruvate ratio Granger-caused increase in intraspinal pressure, decrease in spinal cord perfusion, and decrease in motor score. Causality analysis also revealed multiple vicious cycles that amplify insults to the cord thus exacerbating cord damage. CONCLUSION: Monitoring intraspinal pressure, spinal cord perfusion pressure, lactate-to-pyruvate ratio, and intervening to normalize these parameters are likely to improve limb power

Targeted Perfusion Therapy in Spinal Cord Trauma.

We review state-of-the-art monitoring techniques for acute, severe traumatic spinal cord injury (TSCI) to facilitate targeted perfusion of the injured cord rather than applying universal mean arterial pressure targets. Key concepts are discussed such as intraspinal pressure and spinal cord perfusion pressure (SCPP) at the injury site, respectively, analogous to intracranial pressure and cerebral perfusion pressure for traumatic brain injury. The concept of spinal cord autoregulation is introduced and quantified using spinal pressure reactivity index (sPRx), which is analogous to pressure reactivity index for traumatic brain injury. The U-shaped relationship between sPRx and SCPP defines the optimum SCPP as the SCPP that minimizes sPRx (i.e., maximizes autoregulation), and suggests that not only ischemia but also hyperemia at the injury site may be detrimental. The observation that optimum SCPP varies between patients and temporally in each patient supports individualized management. We discuss multimodality monitoring, which revealed strong correlations between SCPP and injury site metabolism (tissue glucose, lactate, pyruvate, glutamate, glycerol), monitored by surface microdialysis. Evidence is presented that the dura is a major, but unappreciated, cause of spinal cord compression after TSCI; we thus propose expansion duroplasty as a novel treatment. Monitoring spinal cord blood flow at the injury site has revealed novel phenomena, e.g., 3 distinct blood flow patterns, local steal, and diastolic ischemia. We conclude that monitoring from the injured spinal cord in the intensive care unit is a safe technique that appears to enable optimized and individualized spinal cord perfusion

Fully automated grey and white matter segmentation of the cervical cord in vivo

We propose and validate a new fully automated spinal cord (SC) segmentation technique that incorporates two different multi-atlas segmentation propagation and fusion techniques: Optimized PatchMatch Label fusion (OPAL) and Similarity and Truth Estimation for Propagated Segmentations (STEPS). We collaboratively join the advantages of each method to obtain the most accurate SC segmentation. The new method reaches the inter-rater variability, providing automatic segmentations equivalents to inter-rater segmentations in terms of DSC 0.97 for whole cord for any subject

Ultrasonic distance detection for a closed-loop spinal cord stimulation system

When stimulating the spinal cord at a constant strength, the current density in the spinal cord and thus the effects on chronic, intractable pain and vascular insufficiency will change with body position, due to the varying separation of the spinal cord and the stimulating electrode. The current density in the spinal cord has to remain between the perception and discomfort threshold (stimulation window) for a good therapeutic effect, i.e. that the patient does not suffer from pain. The stimulation window is very small. In current SCS systems the stimulus applied to the electrode is set at a constant value. A major improvement could be achieved when the distance between stimulation electrode and spinal cord could be measured and used to control the stimulus amplitude in a closed-loop system. An ultrasonic piezoelectric transducer was chosen to measure the distance between the electrode and the spinal cor

Spinal Cord Trauma: An Overview of Normal Structure and Function, Primary and Secondary Mechanisms of Injury, and Emerging Treatment Modalities

The structures of the spinal cord and vertebral column are designed to provide flexibility, while still providing ample protection for the spinal cord deep within. While it does offer remarkable protection against most routine trauma, the spinal cord is still vulnerable to high-force etiologies of trauma and may become damaged as a result. These events are referred to as primary injury. Following the initial injury, the body’s own physiological responses cause a cascade of deleterious effects, known as secondary injury. Secondary injury is a major therapeutic target in mitigating the effects of spinal cord injury (SCI), and much research is currently being done to develop more effective treatment options

Axonal regeneration in hippocampal and spinal cord organotypic slice cultures

Under normal conditions, axonal regeneration after lesions is not possible in mature CNS but can occur in embryonic and early postnatal nervous systems. In recent years, a number of possible strategies to enhance axonal regeneration and eventually treat spinal cord and brain injuries have been identified, some of which have been used successfully in animal experiments, but till now there is still no successful treatment available for patients. This problem is partly due to the complexity of the animal experiments which makes it difficult to compare different treatment strategies. In this project, we have used organotypic slice culture models to test the effectiveness of pharmacological compounds that interfere with various signal transduction mechanisms, to promote axonal regeneration. We used the entorhino hippocampal slice cultures to assess regeneration of entorhinal fibers projecting to the dentate gyrus after mechanical lesions and treatment. It was previously shown (Prang et. al., 2001) that there is a marked decrease in regenerating fibers when a lesion is made at 6 7 days in vitro or later in slices derived from postnatal day 5 6 mice. We took this as a control model where there is little spontaneous axonal regeneration, added treatments on the day of lesion and later traced for entorhinal axons with biotinylated dextran amine (BDA). In this study it was shown that compounds acting on the cAMP, PKC and G proteins can promote regeneration. Furthermore, we have identified the inhibition of the PI3 kinase pathway and the IP 3 receptor as potential drug targets that promote axonal regeneration. In order to study axonal growth in a spinal cord environment we have developed a spinal cord longitudinal organotypic slice culture model which allowed us to follow axons along the rostro caudal extension of the spinal cord. Slices of cervical spinal cord were cut in the sagittal plane from early postnatal mice and were maintained in culture for various time periods up to 4 weeks. Histological and immunohistochemical stainings of the cultures have shown that these slice cultures maintain the ventro dorsal polarity of the spinal cord and that an intrinsic fibre projection develops which runs along the rostro caudal extension of the spinal cord slice culture. After mechanical lesion, these fibres have the ability to regenerate spontaneously demonstrating the intrinsic ability of the spinal cord for repair, but this ability is decreased with increasing time in culture. During the culture period the axons became myelinated and expressed synaptic markers. These cultures could thus serve also as a model for myelin formation and synaptogenesis. We have analyzed the potential of axons from longitudinal spinal cord cultures to grow into an adjacent slice of cerebellar tissue. We could show that spinal cord axons do enter the cerebellar slice in particular when early postnatal spinal cord is combined with postnatal cerebellum. Pharmacological treatments were used to enhance axonal growth. Similarly to our findings in the entorhino hippocampal model, cAMP activators and PKC inhibitors promoted axonal growth from the spinal cord to the cerebellum. In cocultures of longitudinal spinal cord slices with cortical slices we have shown that fibers from the cortical slices grew extensively into the spinal cord slice and extended caudally for substantial distances. Our results demonstrate that organotypic slice cultures can be a useful tool to study axonal growth and regeneration. Intrinsic spinal cord axons have a considerable potential for spontaneous regeneration in the early postnatal period and are able to grow both through a mechanical lesion and into another tissue. Moreover, compounds interfering with signal transduction mechanisms, particularly cAMP, PKC, PI3 Kinase, G proteins and IP3 receptors, were able to promote axonal growth and regeneration in diverse slice culture models making them interesting drug candidates for the promotion of axonal regeneration

Swimming Rhythm Generation in The Caudal Hindbrain of The Lamprey

The spinal cord has been well established as the site of generation of the locomotor rhythm in vertebrates, but studies have suggested that the caudal hindbrain in larval fish and amphibians can also generate locomotor rhythms. Here, we investigated whether the caudal hindbrain of the adult lamprey (Petromyzon marinus and Ichthyomyzon unicuspis) has the ability to generate the swimming rhythm. The hindbrain-spinal cord transition zone of the lamprey contains a bilateral column of somatic motoneurons that project via the spino-occipital (S-O) nerves to several muscles of the head. In the brainstem-spinal cord-muscle preparation, these muscles were found to burst and contract rhythmically with a left-right alternation when swimming activity was evoked with a brief electrical stimulation of the spinal cord. In the absence of muscles, the isolated brainstem-spinal cord preparation also produced alternating left-right bursts in S-O nerves (i.e., fictive swimming), and the S-O nerve bursts preceded the bursts occurring in the first ipsilateral spinal ventral root. After physical isolation of the S-O region using transverse cuts of the nervous system, the S-O nerves still exhibited rhythmic bursting with left-right alternation when glutamate was added to the bathing solution. We conclude that the S-O region of the lamprey contains a swimming rhythm generator that produces the leading motor nerve bursts of each swimming cycle, which then propagate down the spinal cord to produce forward swimming. The S-O region of the hindbrain-spinal cord transition zone may play a role in regulating speed, turning, and head orientation during swimming in lamprey