Neurogenic heterotopic ossification (NHO) is a disorder of aberrant bone formation affecting one in five patients sustaining a spinal cord injury or traumatic brain injury. Ectopic bone forms around joints in characteristic patterns, causing pain and limiting movement especially around the hip and elbow. Clinical sequelae of neurogenic heterotopic ossification include urinary tract infection, pressure injuries, pneumonia and poor hygiene, making early diagnosis and treatment clinically compelling. However, diagnosis remains difficult with more investigation needed. Our pathophysiological understanding stems from mechanisms of basic bone formation enhanced by evidence of systemic influences from circulating humor factors and perhaps neurological ones. This increasing understanding guides our implementation of current prophylaxis and treatment including the use of non-steroidal anti-inflammatory drugs, bisphosphonates, radiation therapy and surgery and, importantly, should direct future, more effective ones.

Purpose: Spinal cord injury is definitive because the advancement of axon regeneration from cortical cells is blocked.

Material and methods: Research in the field began in 1980 with peripheral nerve grafts positioned between the stumps of the sectioned cord. Regenerated axons entered the grafts but were blocked when they reached the cord. We therefore developed the concept of connecting the fibres of the descending corticospinal cord directly to the nerves of selected muscles. Research was conducted over 22 years, first with rats then with monkeys. Mortality was high due to insufficient intensive care. For the surviving animals, muscles connected to the cord were trophic, moved, and responded to electrical stimulation of the nerve or the cord and presented histological features comparable to those of sutured peripheral nerves.

Results: After obtaining the approval of the national ethics commission, we performed the procedure in a young woman who was fully informed of the risks and volunteered for the operation. Before operating other patients, we decided to wait for the first clinical results. The operation consisted in connecting the corticospinal cord with the glutemus maximus and medius muscles and the quadriceps muscles (bilaterally). We expected to wait two years or more due to the distance between T10 and the innervated muscles. The patient moved and walked earlier than expected. At the present time, she is able to walk 10 to 15 minutes with a walking aid. In the pool, she is even able to climb a few steps. Her improvement continues.

Discussion: Since the innervation arises from the glutamatergic central motoneuron and the normal motor plaque is a cholinergic junction, research is continuing in rats to search for the genes which code for the receptors of the innervated muscle to learn whether the central motoneuron changes its transmittor or the muscle changes its receptors. Curarisation in these rats paralyses the normal muscles while the denervated muscles re-innervated with central motoneurons are not.

Conclusion: Apparently, the receptors of the motor plaque change. Further confirmation is needed.

Aims. The aim of this study was to determine whether total hip arthroplasty (THA) for chronic hip pain due to unilateral primary osteoarthritis (OA) has a beneficial effect on cognitive performance. Methods. A prospective cohort study was conducted with 101 patients with end-stage hip OA scheduled for THA (mean age 67.4 years (SD 9.5), 51.5% female (n = 52)). Patients were assessed at baseline as well as after three and months. Primary outcome was cognitive performance measured by d2 Test of Attention at six months, Trail Making Test (TMT), FAS-test, Rivermead Behavioural Memory Test (RBMT; story recall subtest), and Rey-Osterrieth Complex Figure Test (ROCF). The improvement of cognitive performance was analyzed using repeated measures analysis of variance. Results. At six months, there was significant improvement in attention, working speed and concentration (d2-test; p < 0.001), visual construction and visual memory (ROCF; p < 0.001), semantic memory (FAS-test; p = 0.009), verbal episodic memory (RBMT; immediate recall p = 0.023, delayed recall p = 0.026), as well as pain (p < 0.001) with small to large effect sizes. Attention, concentration, and visual as well as verbal episodic memory improved significantly with medium effect sizes over η. 2. partial. = 0.06. In these cognitive domains the within-group difference exceeded the minimum clinically important difference. Conclusion. THA is associated with clinically relevant postoperative improvement in the cognitive functions of attention, concentration, and memory. These data support the concept of a broad interaction of arthroplasty with central nervous system function. Cite this article: Bone Joint J 2022;104-B(3):331–340

Aims. The modern prevalence of primary tumours causing metastatic bone disease is ill-defined in the oncological literature. Therefore, the purpose of this study is to identify the prevalence of primary tumours in the setting of metastatic bone disease, as well as reported rates of pathological fracture, postoperative complications, 90-day mortality, and 360-day mortality for each primary tumour subtype. Methods. The Premier Healthcare Database was queried to identify all patients who were diagnosed with metastatic bone disease from January 2015 to December 2020. The prevalence of all primary tumour subtypes was tabulated. Rates of long bone pathological fracture, 90-day mortality, and 360-day mortality following surgical treatment of pathological fracture were assessed for each primary tumour subtype. Patient characteristics and postoperative outcomes were analyzed based upon whether patients had impending fractures treated prophylactically versus treated completed fractures. Results. In total, 407,893 unique patients with metastatic bone disease were identified. Of the 14 primary tumours assessed, metastatic bone disease most frequently originated from lung (24.8%), prostatic (19.4%), breast (19.3%), gastrointestinal (9.4%), and urological (6.5%) malignancies. The top five malignant tumours resulting in long bone pathological fracture were renal (5.8%), myeloma (3.4%), female reproductive (3.2%), lung (2.8%), and breast (2.7%). Following treatment of pathological fractures of long bones, 90-day mortality rates were greatest for lung (12.1%), central nervous system (10.5%), lymphoma (10.4%), gastrointestinal (10.1%), and non-renal urinary (10.0%) malignancies. Finally, our study demonstrates improved 90-day and 360-day survival in patients treated for impending pathological fracture compared to completed fracture, as well as significantly lower rates of deep vein thrombosis, pulmonary embolism, urinary tract infection, and blood transfusion. Conclusion. This study defines the contemporary characteristics of primary malignancies resulting in metastatic bone disease. These data should be considered by surgeons when prognosticating patient outcomes during treatment of their metastatic bone disease. Cite this article: Bone Jt Open 2023;4(6):424–431

Physiological studies have revealed that the central nervous system controls groups of muscle fibers in a very efficient manner. Within a single skeletal muscle, the central nervous system independently controls individual muscle segments to produce a particular motor outcome. Mechanomyographic studies on the deltoid muscle have revealed that the deltoid muscle, commonly described as having three anatomical segments, is composed of at least seven functional muscle segments, which all have the potential to be at an important level independently coordinated by the central nervous system.[. 1. ] In this study we tried to anatomically describe and quantify these different functional segments within the deltoid muscle, based on the branching out pattern of the axillary nerve. Forty-four deltoids of 22 embalmed adult cadavers, were analyzed. The axillary nerve was carefully dissected together with his anterior and posterior branch upon invasion into the muscle. According to the pattern of fiber distribution and their fascial embalmment, we then carefully splitted the deltoid muscle into different portions each being innervated by a major branch of the axillary nerve. The position and volume of each segment in relation to the whole muscle was derived. In 3 cases the axillary nerve branched out in 8 major divisions. In 22 out of 44 cases (50%), the axillary nerve branched out in 7 principal parts. A branching out pattern of 6 major divisions occurred in 14 out of 44 cases. Finally we found a division in 5 major branches in 5 of the specimens. In general, both posterior and anterior peripheral segments seemed to have the largest volume. In nearly all (93%) cases, the central segments were smaller in weight and volume compared to the more peripheral segments. Based on the innervation pattern of the deltoid muscle a segmentation in 5 up to 8 major segments seem to be found. This confirms from anatomical point of view earlier reports of functional differentiation within the deltoid muscle

Background. Low back pain can lead to neuroplastic changes in the central nervous system, known as nociplastic pain. As nociplastic pain may be provoked by premorbid sensory profiles, such profiles may be prognostic in the development of nociplastic pain over time. Objectives. To investigate whether four sensory profiles are prognostic in the development of symptoms of nociplastic pain in people with acute low back pain. Methods. A longitudinal type 2 prognostic factor research study was performed in accordance with the PROGRESS framework, using a baseline and a follow-up after 12 weeks, between the Adolescent/Adult Sensory Profile and the Central Sensitisation Inventory. Study participants were consecutively included from primary care physiotherapy practices randomly spread throughout the Netherlands. A multivariable regression analysis was performed to adjust sensory profiles by the level of pain, disability, age, and duration of low back pain. Results. After adjustment Low Registration B=0.41, 95%CI (0.37, 0.99), Sensory Seeking B=0.37, 95%CI (0.24, 0.73), Sensory Sensitive B=0.51, 95%CI (0.50, 1.06), Sensation Avoiding B=0.46, 95%CI (0.43, 0.99) were significantly associated with the development of nociplastic pain symptoms. Conclusion. Sensory profiles in people with acute low back pain predict symptoms of nociplastic pain after 12 weeks. Conflict of interest: No conflict of interest. Sources of funding: No funding obtained

Introduction. Day stay surgery for anterior cruciate ligament (ACL) reconstructions is an increasingly common practice and has driven clinicians to come up with postoperative pain regimes that allow same day mobilisation and a safe and timely discharge. There is a paucity of literature surrounding the use of intraosseous (IO) ropivacaine used as a Bier's block to provide both intraoperative and postoperative analgesia in lower limb surgery. Methods. This patient blinded, pilot study randomised 15 patients undergoing ACL reconstruction to receive either IO ropivacaine 1.5 or 2.0 mg/kg; or 300 mg of ropivacaine as local infiltration (standard of care). Toxic plasma levels of ropivacaine have been defined in the literature and therefore the primary outcome for this study was arterial plasma concentration of ropivacaine as a means to determine its safety profile. Samples were taken via an arterial line at prespecified times after tourniquet deflation. Secondary outcomes that we were interested in included immediate postoperative pain scores using the visual analogue scale (VAS) and perioperative opioid equivalent consumption. Results. Participants had a mean age of 27.8 (SD 9.2) years and 87% (13/15) were male. All patients in the intervention group receiving IO ropivacaine had plasma concentrations well below the threshold for central nervous system (CNS) toxicity (0.60 µg/ml). The highest plasma concentration was achieved in the intervention group receiving 1.5 mg/kg dose of ropivacaine reaching 3.59 mg/ml. This would equate to 0.22 µg/ml of free plasma ropivacaine. There were no differences across the three groups regarding pain scores or perioperative opioid consumption. Conclusions. This study demonstrates that IO administration of 0.2% ropivacaine is both safe and effective in reducing perioperative pain in patients undergoing ACL reconstruction. There may be scope to increase the IO dose further or utilise other analgesics via the IO regional route to improve perioperative pain relief

This Blinded Randomized Clinical Trial outlines: how peri-articular intra-operative multimodal analgesia significantly reduces post-operative analgesia requirement. Sixty-four patients undergoing total knee replacement were randomised to receive a peri-articular intra-operative injection containing ropivacaine, ketorolac, epimorphine and epinephrine or nothing. Patients who received the injection demonstrated greater satisfaction and pain relief. Finally, patients in the injected group did not show any signs of cardio and central nervous system toxicity. Post-operative analgesia can be associated with troublesome side effects. Good peri-operative analgesia facilitates rehabilitation, improves patient satisfaction and may reduce hospital stay. The purpose of this study was to assess a novel cocktail for peri-articular analgesia after total knee replacement. Sixty-four patients undergoing total knee replacement were randomised to receive a peri-articular intra-operative injection containing ropivacaine, ketorolac, epimorphine and epinephrine or nothing. The anaesthetic analgesic regime was standardised. All patients received patient controlled analgesia (PCA) for twenty-four hours post surgery, followed by standard analgesia. VAS pain scores during activity and at rest and patient satisfaction scores were recorded pre and post operatively and at six week follow up. PCA consumption and overall analgesic requirement were measured. PCA use at six, twelve and over twenty-four hours post surgery was significantly less in patients receiving the injection (p< 0.01, p=0.016, p< 0.01). Patient satisfaction in PACU and four hours post operation was greater (p=0.016, p=0.013). VAS for pain during activity in PACU and at four hours were significantly less (p=0.04, p=0.007) in the injected group. The average ROM at six weeks was no different. Overall hospital stay and the incidence of wound complications were not different between the two groups. Peri-articular intra-operative multimodal analgesia significantly reduces post-operative analgesia requirement. Patient satisfaction and pain relief is greater in the injection group. No cardio and central nervous system toxicity was observed. Our novel cocktail of ketorolac, epimorphine, epinephrine and ropivacaine provides superior pain relief with no adverse side effects

Background: Unclear aetiology in scoliotic and kyphotic deformities of the spine are responsible for uncertainty in treatment options. To clarify aetiology a constant reference to what normal growth and optimal construction of the entire spine should be at the end of growth is lacking. Examination of sitting children and consequent testing of muscular tightness can be useful in understanding the different disturbances of growth that keep the spine apparently away from an optimal configuration and thereby optimal function. Prolonged sitting of children exists only 200 years or less. Goal:. - Better understanding of the role of the central nervous system, especially the cord and roots in proper and improper growth of the human spine. - Clarifying that lordosis and good function at the tho-racolumbar junction at the end of growth can be a condition sine qua non for normal configuration and function of the spine in adult life. Methods:. - Present obvious important and consistent clinical observations in children in sitting and supine position with early and advanced adolescent deformities, both kyphotic and scoliotic by photographic studies and video fragments. - Present results of own study in which a lordotic force give significant correction of all curves in Adolescent Idiopathic Scoliosis. - Revisit the, for the greater part unknown, experimental work on growth and deformation of the spine by Milan Roth in German and Czech literature to disclose a tension-based balancing system between central cord and the osseous and discoligamentary spine (uncoupled neuro-osseous growth). - Relate these clinical and experimental findings with common knowledge about adolescent spinal deformities and mechanical laws on tensile and compressive forces in structures. Results: We discovered by alteration of our brace-configuration that applying lordotic forces exclusively on the thoracolumbar spine gives excellent correction of kyphotic and scoliotic deformities progressing in adolescence. In a study of 32 patients with double curves > 25° all scoliotic curves significantly (p< 0,001) reduced by correcting with a forced lordotic fulcrum. Extended clinical examination of children with proven or suspected spinal deformities revealed a complex of consistent findings in different sitting positions and functional tests in supine and standing positions. Discussion: By looking for scientific support for these phenomena in (bio-)mechanical literature the work of Milan Roth was disclosed in his complete width. His embryologic studies, (neuro) anatomical and radiological findings with their explanations, alongside interesting cadaver-, mechanical- and neuro-anatomical experiments and models can bring his concept of neuro-spinal relationship in growth and misgrowth back to orthopaedic daylight. Even Nicoladoni saw a century ago that a cascade of structural alterations take place around the “core”-unit of the spine: the boundaries of the central canal to let it stay on its place and in the shortest configuration possible in scoliosis, by suspected tensile and compressive forces. Anatomical and biomechanical consequences of keeping the spine upright in standing, but more important in the sitting positions seems to fit. Children do sit for prolonged periods only in the last one or two centuries!. It can be shown that the presence of these tension related clinical signs are easily leading to high compressive forces with deformation of the ventral parts in the TL-junction while sitting In literature evidence of torsion facilitating anatomical features can be found to clarify why some spines deform in scoliosis an not in pure kyphosis. Conclusions: By recognising positive effects of creating lordosis at the thoracolumbar junction of the spine and consistent clinical findings in early deformations scientific support was found by early experimental work of Roth. With a leading role of the central nervous system in growth of the spine of standing and sitting vertebrates by steering a tension based system, deformation can be understood as adaptations. Consequences for preventive measures and therapeutic strategies in deformities seems inevitable

Introduction. Spinal deformations are a deviation of the natural arrangement of forces during growth. Environmental factors play a part in these deviations. The presence of lordosis in the thoracic spine is a causative factor in spinal deformations that needs to be addressed. Most biomechanical models of bracing have a scientific background. Has older knowledge lost its value? In living structures, all processes such as regulation of equilibrium in posture and movement use Newton's law and extended laws of Hooke for conservation of energy, momentum, and angular momentum under control of the central nervous system. Form follows function (phylogenetic and ontogenetic) in the spine as primary engine in movement in animals. The change in function in bipedals is that the coupling mechanism at the thoracolumbar joint now couples a reversed pendulum. Methods. A literature search shows a clear gap in the evolution in science on deformities during 1914–45. In 1792, Van Gesscher postulated two concepts in Observations on Deformations of the Spine (Dutch). First, the optimalisation of the balancing forces in men needs a specific optimum curvature to keep the weight of the head and shoulders above the hips. The second concept was the role of sitting in relation to changes around the discs at the thoracolumbar spine. Girls who read or knitted while sitting developed scoliosis more easily than did others. His extending (by lordosis) corrective corset was used for more than 150 years before plaster became popular. Andry described guidance and correction of growing spines with use of the moulding capability of muscular forces, with exercises and extending corsets (for so-called weak girls). Extension and avoidance of incorrect posture during sitting became a mainstay in orthopaedics (and schools). In 1907, Wullstein described experiments in young dogs to show how forced fiexion produces all characteristics of kyphotic deformities. In 1912, Murk Jansen did a critical review of all available knowledge and his own research in The Physiologic Scoliosis and its causes. Post mortem studies showed anatomical asymmetry in the left and right crura of the diaphragm, which indicated that asymmetric rotational forces in ventilation could induce predominant lateral curves. In-vivo tests show increased thoracolumbar kyphosis if siblings are put in seated positions too frequently and too soon. The stiffening in kyphosis creates a fulcrum to cantilever the opposing rotational forces to lateral curvatures. In experiments in rabbits, lower intrathoracic pressure was shown in the right pleural cavity. Common alertness of parents and teachers was underwritten. Some of this still survives. In progressed scoliosis, Sayre's method of corrective plastering in suspension and Calot's corrections in prone position under anaesthesia and plaster shelves with lordosis in bed became popular. In the Volkmann Hueter principle, the resilience of the deformable structures in the spine were identified–eg, the discs, the apophyses, and the cartilage in joints have a role in spinal deformity. Cobb drew attention to the clinical aspects of scoliosis. Roth provided a comprehensive explanation of how growth is organised and regulated by the oldest organ of animal life: the central nervous system in vertebrates. Between 1960 and 1985, Roth developed his concepts on neurovertebral and neuro-osseous growth relations and the tension-driven incongruence of growth. Roth provided new biological knowledge about how growth seems to support older clinical observations. In animal experiments, mechanical modelling, and radiological studies in scoliosis he stressed the role that growth has in the formation of the spine. A so-called short cord can indeed cause scoliosis. Recent studies with MRI in idiopathic scoliosis confirm this hypothesis. Personal observations In 2008, a study showed that forceful restoration of thoracolumbar lordosis can correct double major scoliotic curves. A consequent thoracolumbar kyphotic curve was found, and recently reproduced. The thoracolumbar lordotic intervention brace technique showed promising results. It relied on the older techniques, leaving only the fear for lordosis brought by Dickson. In personal observations, the presence of neuromuscular tightness or tension also present in progressive scoliosis as representatives of deforming and protective forces. Conclusions. Previous knowledge depicts spinal growth as result of a combination of neuro-osseous growth regulation in a very complex but understandable loco-motor system, in which external factors cause muscular reaction that obey all mechanical laws. Lifestyle factors seem to greatly affect deformations

Purpose of the Study. To assess the test-retest reliability, construct validity and determine the cut-off scoret of BACKonLINE™ for people with LBP. Background. Appropriate treatment for Low back pain (LBP) is vital, however patients can wait for 14–24 weeks on NHS Physiotherapy lists. Many factors contribute to LBP and initially can be due to peripheral tissue damage. However, persistent LBP is associated with amplification in pain processing in the central nervous system (central sensitisation-CS). CS often results in poorer outcomes and often requires longer management making timely assessment and appropriate management crucial. An online self-assessment and self-management tool (BACKonLINE™) for discerning between characteristics of predominantly centrally (CD) or peripherally (PD) driven LBP was developed using a Delphi study. Method. Same subject, test-retest reliability and construct validity study (two sessions). Sample of 35 volunteers with LBP. In session 1, participants completed BACKonLINE™ and validated questionnaires (Oswestry Disability Index, StartBack, Tampa scale for Kinesiophobia, Pain Anxiety Symptom Scale Short Form 20). Participants repeated the process one week later. BACKonLINE's Cut-off score was determined by plotting results against StartBack using ROC curve analysis. Results. BACKonLINE™ showed excellent test-retest reliability (ICC= 0.913; 95%CI=0.832–0.956). When assessing construct validity, the aforementioned questionnaires demonstrated moderate correlation with BACKonLINE™ (Pearson's r range= 0.42–0.67, p-value<0.005). ROC analysis determined that scores higher than 42 in BACKonLINE™ indicate CD LBP while scores ≤42 indicate PD LBP. Conclusion. The study shows that BACKonLINE™ has excellent test-retest reliability, and good construct validity within a LBP population. However, further studies with larger sample sizes should be conducted before the implementation of BACKonLINE™. Conflicts of interest: No conflicts of interest. Sources of funding: Civil Service Commission, Kuwait

Purpose of the Study. To develop an online self-assessment and self-management tool (BACKonLINE™) for discerning between people with characteristics of predominantly centrally (CD) or peripherally (PD) driven LBP. Background. Low back pain (LBP) may worsen with time, making appropriate treatment important. In the NHS Physiotherapy services LBP patients may wait for 14–24 weeks for treatments. Many factors contribute to LBP, but it is predominantly initially viewed as a result of peripheral tissue damage. However, evidence show that persistent LBP is associated with amplification in pain processing in the central nervous system (central sensitisation). Sometimes, this may drive symptoms, resulting in poorer outcomes and requiring longer management. Timely assessment and appropriate management is therefore paramount. Method. Design: 2-round Delphi study. Sample: Purposive sample of international LBP physiotherapy experts. For Round1, series of questions were developed using literature search on characterising clinical features of LBP with predominantly CD or PD pain. Participants were asked to score questions on a 7-point Likert scale on their importance in differentiating between CD and PD pain. Round2, sent to Round1 participants, aimed to reach final consensus on BACKonLINE™. Consensus for both rounds was pre-set at ≥70%. Results. In Round1, 38 experts participated. Out of 55 questions, 33 (60%) reached consensus. Participants added 11 new questions. Round2 included 44 questions and sent to Round1 participants. In Round2, 40 (90.9%) questions reached final consensus. Conclusion. This study displays an agreement among LBP physiotherapy experts on the importance of characterising CD and PD pain. Forty (90.9%) questions reached final consensus and formulated BACKonLINE™. Conflicts of interest. No conflicts of interest. Sources of funding. Civil Service Commission, Kuwait

Background:. We have recently shown, using transcranial magnetic stimulation (TMS) to assess voluntary activation (VA), that neural drive to back muscles is reduced in subjects with chronic low back pain. There is also evidence that central nervous system drive to abdominal muscles is altered in these subjects, however VA has not yet been assessed for these muscles in healthy subjects; this is the purpose of the present study. Methods:. Twenty one healthy subjects (10M:11F) participated. Electromyographic activity was recorded from back and abdominal muscles and flexor torque was measured using a dynamometer. Subjects performed a series of isometric voluntary contractions (10%–100% MVC) of rectus abdominis during which TMS was applied to the motor cortex. The resulting superimposed twitches (SIT) were measured and VA was derived. Results:. There was a linear relationship between voluntary torque (50–100% MVC) and SIT amplitude and between voluntary torque (50–100% MVC) and VA. VA at a target torque of 100% MVC was less than maximal (∼86%). Time-to-peak amplitude of SITs displayed a linear relationship with voluntary torque between 10%–100% MVC. Discussion:. This study has shown that it is possible to assess VA of abdominal muscles using TMS. Further, it appears that VA is submaximal during maximum voluntary contractions, similar to that observed in back muscles. This may reflect the function of trunk muscles in general, which are routinely used for maintenance of posture. Whether imbalances of abdominal and back muscle strength observed in low back pain are reflected in imbalances of neural drive to these muscles remains to be investigated

C-type natriuretic peptide is the most abundant natriuretic peptide in the central nervous system. It has been implicated in neurogenesis and may have a significant role in spinal regeneration. We postulated that the spinal concentration of CNP would be reflected in the plasma concentrations of both CNP and the pro-hormone (NTproCNP) and this may be an indicator of repair potential in spinal injuries. Concurrent plasma and CSF concentrations of CNP forms were measured in 51 subjects undergoing spinal anaesthesia for elective total hip and knee replacement. Associations with CNP activity and metabolism in CSF were sought by measuring CSF levels of cGMP and neprilysin respectively. Elevated concentrations of NTproCNP (1045±359 pmol/L) were found in CSF and greatly exceeded those of CNP (7.9±3.2 pmol/L). The ratio of NTproCNP to CNP in CSF (145±55) was much higher than in plasma (31±27). A significant inverse relation was found between plasma and CSF CNP concentrations (r=−0.29, p<0.05). cGMP and neprilysin were unrelated to CNP levels in CSF. Despite markedly elevated levels of NTproCNP in CSF, it is unlikely that these contribute to systemic levels in healthy adults. Identifying NTproCNP as the dominant CNP form in CSF opens up the possibility of its use in future studies exploring CNP regulation within the CNS and possible applications in diagnosis and monitoring of healing in patients with spinal cord injury

Introduction. Changes in the central nervous system (CNS) pathways controlling trunk and leg muscles in patients with low back pain and radiculopathy have been observed and this study investigated whether surgery impacts upon these changes. Methods. Parameters of corticospinal control were examined on 3 occasions in 22 patients prior to, at 6 and 26 weeks following lumbar decompression surgery and in 14 control subjects at the same intervals. Electromyographic activity was recorded from tibialis anterior (TA), soleus (SOL), rectus abdominis (RA), external oblique (EO) and erector spinae (ES) muscles at the T12 & L4 levels in response to transcranial magnetic stimulation of the motor cortex. Results. In the surgical group, asymmetries in the size of motor evoked potentials (MEPs) in TA (P=0.001) and in the cortical silent periods (cSP) were found between the left and right sides in SOL (P=0.005) and ES at L4 (P=0.014) prior to surgery. This was not observed at 6 or 26 weeks. Abdominal responses could be evoked in 12 patients and there was a significant reduction in the cSP contralateral to the pain in EO (P=0.034) and RA (P=0.041) at 6 weeks. These parameters remained stable in controls over time. Discussion. The fact that changes appear to stabilise at 6 weeks is of interest as this parallels clinical outcome studies. Current work is ongoing to examine these excitability changes in both inhibitory and excitatory cortical pathways in these patients, and to what extent they may be related to clinical outcome

Introduction: Changes in the central nervous system (CNS) pathways controlling trunk and leg muscles in patients with low back pain and sciatica have been demonstrated. The aim of this study is to investigate whether these changes are altered by surgery. Methods: Corticospinal excitability was examined on 2 occasions in 15 patients prior to and 6 weeks following lumbar decompression surgery and 7 control subjects – at the same time intervals. This was achieved by recording electromyographic (EMG) activity from tibialis anterior (TA), soleus (SOL), rectus abdominis (RA), external oblique (EO) and erector spinae (ES) muscles at the T12 & L4 levels in response to transcranial magnetic stimulation (TMS) of the motor cortex. Results: A significant asymmetry in the cortical silent period (cSP) between the side ipsilateral to the pain and the contralateral side was found pre- but not post surgery in ES at L4 (P=0.012) and SOL (P=0.039). An asymmetry in the size of motor evoked potentials (MEPs) was also found in TA (P=0.009) which was no longer significant post surgery. Abdominal responses could be recorded in 10 subjects, where significant decreases in contralateral cSP in EO (P=0.021) and RA (P=0.033) were found. In controls no significant differences or changes were found. Discussion: These results show significant asymmetries in the CNS control of trunk and leg muscles in patients prior to surgery to relieve pain which are resolved by the surgery. The degree of change in asymmetry may reflect the variability in surgical outcome. This work is currently ongoing. Conflicts of Interest: None. Funded by: the DISCS foundation

Leptin is a major hormonal product of the adipocyte which regulates appetite and reproductive function through its hypothalamic receptors. It has now become clear that leptin receptors are much more widely distributed than just the hypothalamus, and the skeleton has emerged as an important site of action of leptin. The signalling form of the leptin receptor has been found in several cell types including human osteoblasts, rat osteoblasts and human chondrocytes. In vitro we have shown leptin to an anabolic factor, stimulating osteoblast proliferation and inhibiting osteoclastogenesis. Leptin increases bone mass and reduces bone fragility when administered peripherally but has an indirect inhibitory effect on bone mass via the hypothalamus when administered directly into the central nervous system. Data from animal models where there is an absence of either leptin production (ob/ob) or its receptor (db/db) have been contradictory. In this study we compared the bone phenotype of leptin receptor-deficient (db/db) and wild-type (WT) mice. Micro-CT analysis was done on proximal tibiae using a Skyscan 1172 scanner. Db/db mice had significantly reduced trabecular bone volume, trabecular thickness and trabecular number and a higher degree of trabecular separation. Cortical bone was also significantly lower in db/db animals in volume, cross-sectional thickness and perimeter. These results demonstrate that in the absence of leptin signalling there is reduced bone mass indicating that leptin indeed acts in vivo as a bone anabolic factor, mimicking the in vitro results

Introduction This study was conducted to quantify the incidence of gastrointestinal morbidity and identify risk factors for developing gastrointestinal morbidity following spinal surgery in children. Method A retrospective review was conducted on 253 surgical spinal procedures performed over a 5 year period at Starship Children’s Hospital. Multivariate logistic regression analysis was used to identify significant risk factors. Co-morbidity included co-existing cardiac, respiratory, genitorurinary or central nervous system problems, or delayed development. Results Seventy eight (77.9%) percent of the study population developed gastrointestinal morbidity and this significantly prolonged the median post-operative hospital stay (8 days vs.4 days; p< 0.0001). Emesis (50.6%), paralytic ileus (42.3%) and constipation (22.5%) were the most frequent gastrointestinal morbidities. Significant risk factors for developing gastrointestinal morbidity were fusion surgery (p< 0.01), co-morbidities (p-value) and duration of post-operative opioid use (p-value). Discussion There is a high incidence of gastrointestinal morbidity after paediatric spinal surgery. The consequent prolonged hospital stay has clinical implications to both the patient and the institution. We have further identified risk factors for developing gastrointestinal morbidity, of which the duration of post-operative opioid use is modifiable. Awareness of those with the other significant risk factors identified by this study could assist in the timely implementation of appropriate treatment

Several workers consider that the aetiology of adolescent idiopathic scoliosis (AIS) involves undetected neu-romuscular dysfunction. During normal development the central nervous system (CNS) has to adapt to the rapidly growing skeleton of adolescence, and in AIS also to developing spinal asymmetry from whatever cause. A new etiologic concept is proposed after examining the following evidence:. anomalous extra-spinal left-right skeletal length asymmetries of upper arms, ribs, ilia and lower limbs suggesting that asymmetries may also involve vertebral body and costal growth plates;. growth velocity and curve progression in relation to scoliosis curve expression;. the CNS body schema, parietal lobe and temporoparietal junction in relation to postural mechanisms; and. human upright posture and movements of spine and trunk. The central of four requirements is maturational delay of the CNS body schema relative to skeletal maturation during the adolescent growth spurt that disturbs the normal neuro-osseous timing of maturation. With the development of an early AIS deformity at a time of rapid spinal growth the association of CNS maturational delay results in postural mechanisms failing to balance a lateral spinal deformity in an upright moving trunk that is larger than the information on personal space (self) established in the brain by that time of development. It is postulated that CNS maturational delay allows scoliosis curve progression to occur – unless the delay is temporary when curve progression would cease. The concept brings together many findings relating AIS to the nervous and musculoskeletal systems and suggests brain morphometric studies in subjects with progressive AIS

Introduction. Changes in central nervous system (CNS) pathways controlling trunk and leg muscles in patients with low back pain(LBP) and lumbar radiculopathy have been observed and this study investigated whether surgery impacts upon these changes in the long term. Methods. 80 participants were recruited into the following groups: 25 surgery(S), 20 chronic LBP(CH), 14 spinal injection(SI), and 21 controls(C). Parameters of corticospinal control were examined before, at 6, 26 and 52 weeks following lumbar decompression surgery and equivalent intervals. Electromyographic(EMG) activity was recorded from tibialis anterior(TA), soleus(SOL), rectus abdominis(RA), external oblique(EO) and erector spinae(ES) muscles at the T12&L4 levels in response to transcranial magnetic stimulation of the motor cortex. Motor evoked potentials (MEP) and cortical silent periods(cSP) recruitment curves(RC) were analysed. Results. Trunk muscles in all patients had reduced raw EMG (P<0.001), increased motor thresholds (MTh;P<0.001) and MEP RC slopes. MTh in ESL4 correlated with back pain in all patients (r=0.201, P=0.016) and soleus MTh laterality with disability in surgery patients (r=0.49, P=0.018). S&SI patients displayed bilaterally increased soleus cSP (p<0.001), MEP latencies on the painful side (P<0.001), and cSP asymmetry (cSPA;P<0.001). cSPA resulted from abnormal soleus late responses on the painful side, indicating compromised agonist-antagonist control in patients with radiculopathy. In contrast to SI, surgery significantly reduced soleus cSPA and MEP latencies at 6 weeks (P≤0.034). Discussion. These results show long term changes in CNS control of trunk and leg muscles in radiculopathy and LBP, which are only partly reversed by surgery, and may provide future therapeutic targets to address the altered inhibitory processes within the brain. No conflicts of Interest. Sources of funding: The DISCS foundation. This abstract has not been previously published in whole or substantial part nor has it been presented previously at a national meeting