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1.  A patient presenting with intact sensory modalities in acute spinal cord ischemia syndrome: a case report 
Introduction
Acute spinal cord ischemia syndrome is a rare condition comprising a small fraction of neurovascular accidents, the majority of which occur within the cerebral circulation. The circulation of the spinal cord has several unique features that determine the clinical presentation.
Case presentation
In this case of a 67-year-old Caucasian man who came to our emergency department with sudden-onset, severe right-sided pain and bilateral upper limb weakness, an atypical pattern of sensory deficit was observed. In this case report, we review acute spinal cord ischemia syndrome and consider the pathophysiology, diagnostic measures and prognostic factors associated with patient recovery.
Conclusion
Acute spinal cord ischemia syndrome with atypical patterns of sensory deficit is uncommon. Clinicians must consider acute spinal cord ischemia syndrome when assessing all patients with acute neck pain and focal neurological deficits; atypical presentations can present a diagnostic challenge. Current knowledge of the long-term outcome in patients with spinal cord ischemia is based on only a few small studies, some of which are discussed here.
doi:10.1186/1752-1947-5-31
PMCID: PMC3224536  PMID: 21269425
2.  Transplanted astrocytes derived from BMP- or CNTF-treated glial-restricted precursors have opposite effects on recovery and allodynia after spinal cord injury 
Journal of Biology  2008;7(7):24.
Background
Two critical challenges in developing cell-transplantation therapies for injured or diseased tissues are to identify optimal cells and harmful side effects. This is of particular concern in the case of spinal cord injury, where recent studies have shown that transplanted neuroepithelial stem cells can generate pain syndromes.
Results
We have previously shown that astrocytes derived from glial-restricted precursor cells (GRPs) treated with bone morphogenetic protein-4 (BMP-4) can promote robust axon regeneration and functional recovery when transplanted into rat spinal cord injuries. In contrast, we now show that transplantation of GRP-derived astrocytes (GDAs) generated by exposure to the gp130 agonist ciliary neurotrophic factor (GDAsCNTF), the other major signaling pathway involved in astrogenesis, results in failure of axon regeneration and functional recovery. Moreover, transplantation of GDACNTF cells promoted the onset of mechanical allodynia and thermal hyperalgesia at 2 weeks after injury, an effect that persisted through 5 weeks post-injury. Delayed onset of similar neuropathic pain was also caused by transplantation of undifferentiated GRPs. In contrast, rats transplanted with GDAsBMP did not exhibit pain syndromes.
Conclusion
Our results show that not all astrocytes derived from embryonic precursors are equally beneficial for spinal cord repair and they provide the first identification of a differentiated neural cell type that can cause pain syndromes on transplantation into the damaged spinal cord, emphasizing the importance of evaluating the capacity of candidate cells to cause allodynia before initiating clinical trials. They also confirm the particular promise of GDAs treated with bone morphogenetic protein for spinal cord injury repair.
doi:10.1186/jbiol85
PMCID: PMC2776404  PMID: 18803859
3.  How Well Do Clinical Pain Assessment Tools Reflect Pain in Infants? 
PLoS Medicine  2008;5(6):e129.
Background
Pain in infancy is poorly understood, and medical staff often have difficulty assessing whether an infant is in pain. Current pain assessment tools rely on behavioural and physiological measures, such as change in facial expression, which may not accurately reflect pain experience. Our ability to measure cortical pain responses in young infants gives us the first opportunity to evaluate pain assessment tools with respect to the sensory input and establish whether the resultant pain scores reflect cortical pain processing.
Methods and Findings
Cortical haemodynamic activity was measured in infants, aged 25–43 wk postmenstrual, using near-infrared spectroscopy following a clinically required heel lance and compared to the magnitude of the premature infant pain profile (PIPP) score in the same infant to the same stimulus (n = 12, 33 test occasions). Overall, there was good correlation between the PIPP score and the level of cortical activity (regression coefficient = 0.72, 95% confidence interval [CI] limits 0.32–1.11, p = 0.001; correlation coefficient = 0.57). Of the different PIPP components, facial expression correlated best with cortical activity (regression coefficient = 1.26, 95% CI limits 0.84–1.67, p < 0.0001; correlation coefficient = 0.74) (n = 12, 33 test occasions). Cortical pain responses were still recorded in some infants who did not display a change in facial expression.
Conclusions
While painful stimulation generally evokes parallel cortical and behavioural responses in infants, pain may be processed at the cortical level without producing detectable behavioural changes. As a result, an infant with a low pain score based on behavioural assessment tools alone may not be pain free.
Rebeccah Slater and colleagues show that although painful stimulation generally evokes parallel cortical and behavioral responses in infants, pain may produce cortical responses without detectable behavioral changes.
Editors' Summary
Background.
Pain is a sensory and emotional experience. It is normally triggered by messages transmitted from specialized receptors (nociceptors) in the body to integrative centers in the spinal cord and brainstem and on to the brain, where it undergoes higher sensory and cognitive analysis, allowing the body to respond appropriately to the stimuli. While the experience of pain may be considered to be unpleasant, it is a useful tool in communicating to us and to others that there is something wrong with our bodies. Ultimately, these responses help restrict further damage to the body and start the process of healing.
In a clinical setting, the ability to communicate about pain allows an individual to seek strategies to ease the pain, such as taking analgesics. Being unable to effectively communicate one's experience of pain leaves the individual vulnerable to prolonged suffering. One such vulnerable group is infants.
Ignored and untreated pain in infants has been shown to have immediate and long-term effects as a result of structural and physiological changes within the nervous system. For example, the body responds to untreated pain by increased release of stress hormones, which may be associated with increased morbidity and mortality in the short term. Long-term effects of pain may include altered pain perception, chronic pain syndromes, and somatic complaints such as sleep disturbances, feeding problems, and inability to self-regulate in response to internal and external stressors. It has been proposed that attention deficit disorders, learning disorders, and behavioral problems in later childhood may be linked to repetitive pain in the preterm infant.
Why Was This Study Done?
Until as recently as the 1990s, newborns in some clinical centres underwent surgery with minimal anesthesia. Also, newborns received little or no pain management postoperatively or for painful procedures such as lumbar punctures or circumcisions. Since then, there has been growing awareness amongst clinicians that pain may be experienced from the earliest stages of postnatal life and that inadequate analgesia may lead to the type of long-term consequences mentioned above. However, gauging how much pain infants and young children are experiencing remains a substantial challenge. The researchers in this study wanted to assess the association between cortical pain responses in young infants and currently used tools for the assessment of pain in these infants. These current tools are based on behavioral and physiological measures, such as change in facial expression, and it is possible that these tools do not give an adequate measure of pain especially in infants born preterm.
What Did the Researchers Do and Find?
Twelve clinically stable infants were studied on 33 occasions when they required a heel lance to obtain a blood sample for a clinical reason. The researchers examined the relationship between brain activity and a clinical pain score, calculated using the premature infant pain profile (PIPP) in response to a painful event. Activity in the somatosensory cortex was measured noninvasively by near-infrared spectroscopy, which measures brain regional changes in oxygenated and deoxygenated hemoglobin concentration. The PIPP is a well-established pain score that ascribes a value to infant behavior such as change in facial expression.
They found that changes in brain activity in response to a painful stimulus were related to the PIPP scores. These changes were more strongly linked to the behavioral components of the PIPP, e.g., facial expression, than physiological components, e.g., heart rate. They also found that a positive brain response could occur in the absence of any facial expression.
What Do These Findings Mean?
Behaviors to communicate pain require motor responses to sensory and emotional stimuli. The maturity of this complex system in infants is not clearly understood. The results of this study raise further awareness of the ability of infants to experience pain and highlight the possibility that pain assessment based on behavioral tools alone may underestimate the pain response in infants.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050129.
Important papers on pain in human neonates are discussed in the open access Paediatric Pain Letter with links to original articles
The Institute of Child Health in London has a Web site describing a three-year international project on improving the assessment of pain in hospitalized children, with many useful links
The International Association for the Study of Pain (IASP) provides accurate and up-to-date information and links about pain mechanisms and treatment
doi:10.1371/journal.pmed.0050129
PMCID: PMC2504041  PMID: 18578562
4.  Pain in the three spinal regions: the same disorder? Data from a population-based sample of 34,902 Danish adults 
Background
Studies of back pain are typically based on the assumption that symptoms from different parts of the spine are distinctive entities. Recently, however, the assumption that back pain is a site-specific disorder has been challenged, suggesting that localized back pain should be seen as part of a general musculoskeletal syndrome.
Objectives
To describe and compare the patterns of reporting of pain and consequences of pain in the three spinal regions.
Methods
In all, 34,902 (74%) twin individuals representative of the general Danish population, aged 20 to 71, participated in a cross-sectional nation-wide survey. Identical questions from the Standardised Nordic Questionnaire for each of the three spinal regions were used for lumbar, mid-back and neck pain respectively: Pain past year, pain ever, radiating pain, and consequences of back pain (care-seeking, reduced physical activities, sick-leave, change of work/work duties and disability pension). The relative prevalence estimates of these variables were compared for the three spinal regions.
Results
The relative proportions of individuals with pain ever, who also reported to have had pain in the past year varied between 75% and 80%, for the three spinal regions. The proportions of individuals with pain in the past year and for various pain durations were also very similar. Regardless if pain was reported in the lumbar, thoracic or cervical regions, the proportions of individuals reporting radiating pain were equally large. The relative number of consequences was the same across the spinal regions, as were the relative proportions of each these consequences. However, low back pain resulted more often in some kind of consequence compared to the consequences of pain in the neck and mid back.
Conclusions
Back pain and its consequences share many characteristics and may, at least in a general population, be regarded as the same condition regardless of where the pain happens to manifest itself. However, because some exceptions were noted for the lumbar spine, separate entities for a smaller group of individuals with back pain cannot be ruled out.
doi:10.1186/2045-709X-20-11
PMCID: PMC3368748  PMID: 22480304
5.  Brown-Séquard syndrome in a 11-year-old girl due to penetrating glass injury to the thoracic spine 
Injuries in children are one of the most frequent causes of high morbidity and mortality, and they present a challenge to the treating physician. Fortunately, spinal trauma in pediatric patient is relatively rare. Brown-Séquard syndrome is a rare form of incomplete spinal cord injury consisting of ipsilateral upper motor neuron paralysis (hemiplegia) and loss of proprioception with contralateral pain and temperature sensation deficits resulting from hemisection or lateral injury to the spinal cord. A 11-year-old girl was admitted to our Pediatric Trauma Emergency Department after she had suffered a penetrating back injury. Neurological examination demonstrated left lower extremity paresis and moderate spastic paralysis of the right lower extremity. The examination showed loss of temperature sensation contralateral to and below the lesion. The examination of the pain sensation was difficult because the patient was in pain shock, but it was diminished on the side opposite to the damage. Multislice spiral computed tomography (MSCT) demonstrated a triangular foreign body in spinal canal at the level of the Th11–Th12. After a Th11–L2 laminectomy and retrieval of foreign bodies, dura repair was performed. Patient was discharged from the hospital with partial recovery. Operative decompression of the neural elements in case of spinal canal compromise is the treatment of choice. Indication for surgical intervention in existing cerebrospinal fluid fistula includes closure of the dura and reducing neural elements compression and lowering the risk of infectious complications by removing bone or foreign body fragments. Patients with Brown-Séquard syndrome have good prognosis for functional recovery.
doi:10.1007/s00590-012-1050-8
PMCID: PMC3825641  PMID: 23412183
Brown-Séquard syndrome; Spinal cord injury; Stab wound
6.  Extensive Neuronal Differentiation of Human Neural Stem Cell Grafts in Adult Rat Spinal Cord 
PLoS Medicine  2007;4(2):e39.
Background
Effective treatments for degenerative and traumatic diseases of the nervous system are not currently available. The support or replacement of injured neurons with neural grafts, already an established approach in experimental therapeutics, has been recently invigorated with the addition of neural and embryonic stem-derived precursors as inexhaustible, self-propagating alternatives to fetal tissues. The adult spinal cord, i.e., the site of common devastating injuries and motor neuron disease, has been an especially challenging target for stem cell therapies. In most cases, neural stem cell (NSC) transplants have shown either poor differentiation or a preferential choice of glial lineages.
Methods and Findings
In the present investigation, we grafted NSCs from human fetal spinal cord grown in monolayer into the lumbar cord of normal or injured adult nude rats and observed large-scale differentiation of these cells into neurons that formed axons and synapses and established extensive contacts with host motor neurons. Spinal cord microenvironment appeared to influence fate choice, with centrally located cells taking on a predominant neuronal path, and cells located under the pia membrane persisting as NSCs or presenting with astrocytic phenotypes. Slightly fewer than one-tenth of grafted neurons differentiated into oligodendrocytes. The presence of lesions increased the frequency of astrocytic phenotypes in the white matter.
Conclusions
NSC grafts can show substantial neuronal differentiation in the normal and injured adult spinal cord with good potential of integration into host neural circuits. In view of recent similar findings from other laboratories, the extent of neuronal differentiation observed here disputes the notion of a spinal cord that is constitutively unfavorable to neuronal repair. Restoration of spinal cord circuitry in traumatic and degenerative diseases may be more realistic than previously thought, although major challenges remain, especially with respect to the establishment of neuromuscular connections.
When neural stem cells from human fetal spinal cord were grafted into the lumbar cord of normal or injured adult nude rats, substantial neuronal differentiation was found.
Editors' Summary
Background.
Every year, spinal cord injuries, many caused by road traffic accidents, paralyze about 11,000 people in the US. This paralysis occurs because the spinal cord is the main communication highway between the body and the brain. Information from the skin and other sensory organs is transmitted to the brain along the spinal cord by bundles of neurons, nervous system cells that transmit and receive messages. The brain then sends information back down the spinal cord to control movement, breathing, and other bodily functions. The bones of the spine normally protect the spinal cord but, if these are broken or dislocated, the spinal cord can be cut or compressed, which interrupts the information flow. Damage near the top of the spinal cord can paralyze the arms and legs (tetraplegia); damage lower down paralyzes the legs only (paraplegia). Spinal cord injuries also cause many other medical problems, including the loss of bowel and bladder control. Although the deleterious effects of spinal cord injuries can be minimized by quickly immobilizing the patient and using drugs to reduce inflammation, the damaged nerve fibers never regrow. Consequently, spinal cord injury is permanent.
Why Was This Study Done?
Scientists are currently searching for ways to reverse spinal cord damage. One potential approach is to replace the damaged neurons using neural stem cells (NSCs). These cells, which can be isolated from embryos and from some areas of the adult nervous system, are able to develop into all the specialized cells types of the nervous system. However, because most attempts to repair spinal cord damage with NSC transplants have been unsuccessful, many scientists believe that the environment of the spinal cord is unsuitable for nerve regeneration. In this study, the researchers have investigated what happens to NSCs derived from the spinal cord of a human fetus after transplantation into the spinal cord of adult rats.
What Did the Researchers Do and Find?
The researchers injected human NSCs that they had grown in dishes into the spinal cord of intact nude rats (animals that lack a functioning immune system and so do not destroy human cells) and into nude rats whose spinal cord had been damaged at the transplantation site. The survival and fate of the transplanted cells was assessed by staining thin slices of spinal cord with an antibody that binds to a human-specific protein and with antibodies that recognize proteins specific to NSCs, neurons, or other nervous system cells. The researchers report that the human cells survived well in the adult spinal cord of the injured and normal rats and migrated into the gray matter of the spinal cord (which contains neuronal cell bodies) and into the white matter (which contains the long extensions of nerve cells that carry nerve impulses). 75% and 60% of the human cells in the gray and white matter, respectively, contained a neuron-specific protein six months after transplantation but only 10% of those in the membrane surrounding the spinal cord became neurons; the rest developed into astrocytes (another nervous system cell type) or remained as stem cells. Finally, many of the human-derived neurons made the neurotransmitter GABA (one of the chemicals that transfers messages between neurons) and made contacts with host spinal cord neurons.
What Do These Findings Mean?
These findings suggest that human NSC grafts can, after all, develop into neurons (predominantly GABA-producing neurons) in normal and injured adult spinal cord and integrate into the existing spinal cord if the conditions are right. Although these animal experiments suggest that NSC transplants might help people with spinal injuries, they have some important limitations. For example, the spinal cord lesions used here are mild and unlike those seen in human patients. This and the use of nude rats might have reduced the scarring in the damaged spinal cord that is often a major barrier to nerve regeneration. Furthermore, the researchers did not test whether NSC transplants provide functional improvements after spinal cord injury. However, since other researchers have also recently reported that NSCs can grow and develop into neurons in injured adult spinal cord, these new results further strengthen hopes it might eventually be possible to use human NSCs to repair damaged spinal cords.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/doi:10.1371/journal.pmed.0040039.
The US National Institute of Neurological Disorders and Stroke provides information on spinal cord injury and current spinal cord research
Spinal Research (a UK charity) offers information on spinal cord injury and repair
The US National Spinal Cord Injury Association Web site contains factsheets on spinal cord injuries
MedlinePlus encyclopedia has pages on spinal cord trauma and interactive tutorials on spinal cord injury
The International Society for Stem Cell Research offers information on all sorts of stem cells including NSCs
The US National Human Neural Stem Cell Resource provides information on human NSCs, including the current US government's stance on stem cell research
doi:10.1371/journal.pmed.0040039
PMCID: PMC1796906  PMID: 17298165
7.  Surgical treatment of scoliosis in Rubinstein-Taybi syndrome type 2: a case report 
Introduction
Rubinstein-Taybi syndrome is an autosomal dominant disorder resulting in congenital craniofacial deformities, and divided into types 1 and 2. Scoliosis has not been reported as one of the extra-cranial manifestations of Rubinstein-Taybi syndrome type 2.
Case presentation
We present a 14-year-old British Caucasian girl with Rubinstein-Taybi type 2 syndrome who developed a severe double thoracic scoliosis measuring 39° and 68° respectively. Her scoliosis was associated with thoracic hypokyphosis, causing a marked reduction in the anteroposterior diameter of her chest and consequent severe restrictive lung disease. The deformity was noted by her local pediatrician as part of a chest infection assessment when she was aged 13 years, and gradually progressed as the result of spinal growth. Our patient underwent a posterior spinal arthrodesis using a single concave pedicle hook and screw rod construct and locally harvested autologous graft supplemented by allograft bone. This spinal fixation technique was selected because of our patient’s low body weight to avoid prominence of the instrumentation causing skin healing problems and pain. Her scoliosis was corrected to 18° and 30° and we achieved a balanced spine in the coronal and sagittal planes. An underarm spinal jacket was provided for six months after surgery. During her latest follow-up at skeletal maturity, our patient had an excellent cosmetic outcome with no loss of deformity correction or detected pseudoarthrosis and a normal level of activities.
Conclusion
Scoliosis can develop in young children with Rubinstein-Taybi syndrome type 2, with the deformity deteriorating around the pubertal growth spurt. Surgical treatment can correct the deformity, balance the spine and prevent mechanical back pain. It can also stabilize the chest area and avoid respiratory complications developing as the scoliosis progresses, which can result in severe restrictive pulmonary disease. The use of single concave instrumentation is indicated in very slim patients with poor muscle bulk; in our patient, this produced satisfactory deformity correction and a favorable outcome at completion of growth. Peri-operative care in this group of patients can be very challenging because of associated co-morbidities as well as the presence of severe behavioral issues that result in poor patient compliance.
doi:10.1186/1752-1947-9-10
PMCID: PMC4334754  PMID: 25596810
Posterior spinal fusion; Rubinstein-Taybi syndrome; Scoliosis; Surgical treatment
8.  Long-term experience with implanted intrathecal drug administration systems for failed back syndrome and chronic mechanical low back pain 
Background
Continuous intrathecal drug delivery has been shown in open studies to improve pain and quality of life in those with intractable back pain who have had spinal surgery. There is limited data on long term effects and and even less for patients with mechanical back pain without prior spinal surgery.
Methods
We have investigated spinal drug administration systems for patients with failed back syndrome and chronic mechanical low back pain by patient questionnaire study of the efficacy of this therapy and a case notes review.
Results
36 patients (97% of 37 approached) completed questionnaires, 24 with failed back syndrome and 12 with chronic mechanical low back pain. Recalled pre-treatment levels with current post-treatment levels of pain and a range of quality of life measures (recorded on 11-point numerical rating scales) were compared. Pain improved significantly in both groups (Wilcoxan signed ranks test, p < 0.005). The majority of quality of life measures improved significantly in the failed back syndrome group (Wilcoxan signed ranks test, p < 0.005) although work interruption and the effect of pain on sex life did not change. There was a trend towards improvement in the majority of quality of life measures in the mechanical back pain group but this did not reach statistical significance due to the smaller numbers in this cohort (p > 0.005, Wilcoxan signed ranks test with Bonferroni correction).
Diamorphine was used in all 37 patients, bupivacaine in 32, clonidine in 27 and baclofen in 3. The mean dose of diamorphine increased for the first 2 years but did not change 2–6 years post implant, averaging 4.5 mg/day. Revision surgery was required in 24% of cases, but reduced to 12% in the later years of our experience.
Conclusions
We conclude that spinal drug administration systems appear to be of benefit in alleviating pain in the failed back syndrome and chronic mechanical low back pain but need to be examined prospectively.
doi:10.1186/1471-2474-3-17
PMCID: PMC116675  PMID: 12076357
9.  Pelvic Pain as an Unusual First Presentation of a Demyelinating Disease 
Journal of General Internal Medicine  2008;23(11):1917-1920.
Pelvic pain as the presenting symptom of demyelinating disease is rare. We report on a 49-year-old female patient that initially had symptoms of pain and anesthesia in the perineum. Symptoms later evolved to include both lower and upper extremity weakness and were associated with enhancing spinal cord lesions on MRI. Recognizing that the patient’s disease was localized only to the spinal cord led to an eventual serological diagnosis of neuromyelitis optica (Devic’s disease), a demyelinating syndrome that is now considered distinct from multiple sclerosis and that primarily affects the spinal cord and optic nerves. Pelvic pain is an unusual first presentation of this illness. Additionally, this case illustrates the challenges of establishing a diagnosis of neuromyelitis optica. Recognizing the distinct clinical features of this rare illness, referring specifically from a spinal cord or ophthalmogical etiology, is essential for its rapid diagnosis, and hence for initiation of appropriate therapy.
doi:10.1007/s11606-008-0767-x
PMCID: PMC2585687  PMID: 18769978
demyelinating disease; pelvic pain; neuromyelitis optica (Devic's disease)
10.  Limited access surgery for 360 degrees in-situ fusion in a dysraphic patient with high-grade spondylolisthesis 
European Spine Journal  2011;21(3):390-395.
Progressive high-grade spondylolisthesis can lead to spinal imbalance. High-grade spondylolisthesis is often reduced and fused in unbalanced pelvises, whereas in-situ fusion is used more often in balanced patients. The surgical goal is to recreate or maintain sagittal balance but if anatomical reduction is necessary, the risk of nerval damage with nerve root disruption in worst cases is increased. Spinal dysraphism like spina bifida or tethered cord syndrome make it very difficult to achieve reduction and posterior fusion due to altered anatomy putting the focus on anterior column support. Intensive neural structure manipulation should be avoided to reduce neurological complications and re-tethering in these cases. A 26-year-old patient with a history of diastematomyelia, occult spina bifida and tethered cord syndrome presented with new onset of severe low back pain, and bilateral L5/S1 sciatica after a fall. The X-ray demonstrated a grade III spondylolisthesis with spina bifida and the MRI scan revealed bilateral severely narrowed exit foramina L5 due to the listhesis. Because she was well balanced sagittally, the decision for in-situ fusion was made to minimise the risk of neurological disturbance through reduction. Anterior fusion was favoured to minimise manipulation of the dysraphic neural structures. Fusion was achieved via isolated access to the L4/L5 disc space. A L5 transvertebral hollow modular anchorage (HMA) screw was passed into the sacrum from the L4/L5 disc space and interbody fusion of L4/L5 was performed with a cage. The construct was augmented with pedicle screw fixation L4–S1 via a less invasive bilateral muscle split for better anterior biomechanical support. The postoperative course was uneventful and fusion was CT confirmed at the 6-month follow-up. At the last follow-up, she worked full time, was completely pain free and not limited in her free-time activities. The simultaneous presence of high-grade spondylolisthesis and spinal dysraphism make it very difficult to find a decisive treatment plan because both posterior and anterior treatment strategies have advantages and disadvantages in these challenging cases. The described technique combines several surgical options to achieve 360° fusion with limited access, reducing the risk of neurological sequelae.
doi:10.1007/s00586-011-1994-0
PMCID: PMC3296860  PMID: 22008862
High-grade spondylolisthesis; In-situ fusion; HMA screw; Tethered cord; Spina bifida
11.  McKenzie diagnosis and therapy in the evaluation and management of a lumbar disc derangement syndrome: A case study 
Abstract
Objective
To discuss the case of a patient whose lumbar disc derangement syndrome resolved after treatment that included McKenzie diagnosis and therapy, spinal mobilization, and spinal manipulation. Also, to give an overview of the McKenzie method in general, and more specifically for evaluation and management of derangement syndrome.
Clinical Features
The patient reported acute onset of left-sided low back pain and superior buttock pain while bending to tie her shoes. The most significant finding on initial McKenzie evaluation was that repetitive patient-generated left-side gliding movements greatly increased lumbar range of motion and decreased the buttock and low back pain, with the pain remaining better after completion of the movements.
Intervention and Outcome
The case was initially managed with instructions in patient-generated lateral side-gliding movements and spinal mobilization. After 5 treatment visits, the management was changed to patient-generated repetitive extension movements and spinal manipulation. The outcome was complete resolution as per Oswestry Low Back Pain and Disability Index and Visual Analog Scale, and complete resolution of symptoms except for mild pain with sitting over 2 hours.
Conclusion
This case demonstrated short-term resolution of acute low back pain and buttock pain with patient-generated forces, spinal mobilization and manipulation, and interferential electrical stimulation. McKenzie mechanical diagnosis and therapy may be a beneficial tool in the chiropractic practice.
doi:10.1016/S0899-3467(07)60044-5
PMCID: PMC2646960  PMID: 19674597
Intervertebral Disc; Chiropractic Manipulation; Physical Therapy/Exercise Therapy
12.  Marfan syndrome and symptomatic sacral cyst: Report of two cases 
Context
Meningeal abnormalities such as dural ectasia are seen in Marfan syndrome, but spinal meningeal cysts are rarely seen. These cysts usually asymptomatic and often found incidentally on magnetic resonance imaging, large cysts may cause neurological deficits and pain secondary to nerve root compression.
Design
Case reports.
Findings
Two patients with Marfan syndrome presented with urinary symptoms secondary to dural ectasia and sacral cysts. Patient 1 had a history of low back pain, erectile dysfunction, and occasional urinary incontinence and groin pain with recent symptom worsening. He underwent L5 partial laminectomy and S1-S2 laminectomy with sacral cyst decompression. Nine weeks later, he underwent drainage of a sacral pseudomeningocele. Pain and urinary symptoms resolved, and he remains neurologically normal 2 years after surgery. Patient 2 presented after a fall on his tailbone, complaining of low back pain and difficulty urinating. Physical therapy was implemented, but after 4 weeks, urinary retention had not improved. He then underwent resection of the sacral cyst and S1-S3 laminectomy. Pain and paresthesias resolved and bowel function returned to normal. Other than needing intermittent self-catheterization, all other neurologic findings were normal 30 months after surgery.
Conclusion/clinical relevance
Surgical goals for sacral cysts include resection as well as closure of the dura, which can be challenging due to thinning from ectasia. Neurosurgical intervention in Marfan syndrome is associated with a high risk of dural tears and osseous complications, and should be performed only when symptoms are severe.
doi:10.1179/2045772312Y.0000000079
PMCID: PMC3739900  PMID: 23941798
Cerebrospinal fluid leak; Ectasia; Dura mater; Marfan syndrome; Sacral perineural cyst; Urinary dysfunction; Spine surgery; Laminectomy
13.  Achondroplasia manifesting as enchondromatosis and ossification of the spinal ligaments: a case report 
Introduction
A girl presented with achondroplasia manifested as mild knee pain associated with stiffness of her back. A skeletal survey showed enchondroma-like metaphyseal dysplasia and ossification of the spinal ligaments. Magnetic resonance imaging of the spine further clarified the pathological composites.
Case presentation
A 7-year-old girl presented with the classical phenotypic features of achondroplasia. Radiographic documentation showed the co-existence of metaphyseal enchondromatosis and development of spinal bony ankylosis. Magnetic resonance imaging showed extensive ossification of the anterior and posterior spinal ligaments. Additional features revealed by magnetic resonance imaging included calcification of the peripheral vertebral bodies associated with anterior end-plate irregularities.
Conclusion
Enchondromas are metabolically active and may continue to grow and evolve throughout the patient's lifetime; thus, progressive calcification over a period of years is not unusual. Ossification of the spinal ligaments has a specific site of predilection and often occurs in combination with senile ankylosing vertebral hyperostosis. Nevertheless, ossification of the spinal ligaments has been encountered in children with syndromic malformation complex. It is a multifactorial disease in which complex genetic and environmental factors interact, potentially leading to chronic pressure on the spinal cord and nerve roots with subsequent development of myeloradiculopathy. Our patient presented with a combination of achondroplasia, enchondroma-like metaphyseal dysplasia and calcification of the spinal ligaments. We suggest that the development of heterotopic bone formation along the spinal ligaments had occurred through an abnormal ossified enchondral mechanism. We postulate that ossification of the spinal ligaments and metaphyseal enchondromatous changes are related to each other and represent impaired terminal differentiation of chondrocytes in this particular case. Standard radiographic examination showed spinal bony ankylosis only. The pathological composites of the vertebrae have been clarified using scanning technology. Extensive spinal ligament ossification associated with calcification of the peripheral vertebral bodies and anterior end-plate irregularities were notable. We report what may be a novel spinal and extraspinal malformation complex in a girl with achondroplasia.
doi:10.1186/1752-1947-2-263
PMCID: PMC2518559  PMID: 18694487
14.  Spinal cord stimulation for predominant low back pain in failed back surgery syndrome: study protocol for an international multicenter randomized controlled trial (PROMISE study) 
Trials  2013;14:376.
Background
Although results of case series support the use of spinal cord stimulation in failed back surgery syndrome patients with predominant low back pain, no confirmatory randomized controlled trial has been undertaken in this patient group to date. PROMISE is a multicenter, prospective, randomized, open-label, parallel-group study designed to compare the clinical effectiveness of spinal cord stimulation plus optimal medical management with optimal medical management alone in patients with failed back surgery syndrome and predominant low back pain.
Method/Design
Patients will be recruited in approximately 30 centers across Canada, Europe, and the United States. Eligible patients with low back pain exceeding leg pain and an average Numeric Pain Rating Scale score ≥5 for low back pain will be randomized 1:1 to spinal cord stimulation plus optimal medical management or to optimal medical management alone. The investigators will tailor individual optimal medical management treatment plans to their patients. Excluded from study treatments are intrathecal drug delivery, peripheral nerve stimulation, back surgery related to the original back pain complaint, and experimental therapies. Patients randomized to the spinal cord stimulation group will undergo trial stimulation, and if they achieve adequate low back pain relief a neurostimulation system using the Specify® 5-6-5 multi-column lead (Medtronic Inc., Minneapolis, MN, USA) will be implanted to capture low back pain preferentially in these patients. Outcome assessment will occur at baseline (pre-randomization) and at 1, 3, 6, 9, 12, 18, and 24 months post randomization. After the 6-month visit, patients can change treatment to that received by the other randomized group. The primary outcome is the proportion of patients with ≥50% reduction in low back pain at the 6-month visit. Additional outcomes include changes in low back and leg pain, functional disability, health-related quality of life, return to work, healthcare utilization including medication usage, and patient satisfaction. Data on adverse events will be collected. The primary analysis will follow the intention-to-treat principle. Healthcare use data will be used to assess costs and long-term cost-effectiveness.
Discussion
Recruitment began in January 2013 and will continue until 2016.
Trial registration
Clinicaltrials.gov: NCT01697358 (http://www.clinicaltrials.gov)
doi:10.1186/1745-6215-14-376
PMCID: PMC4226255  PMID: 24195916
Low back pain; Neuropathic pain; Failed back surgery syndrome; Spinal cord stimulation; Randomized controlled trial
15.  Spinal Cord Stimulation for Neuropathic Pain 
Executive Summary
Objective
The objective of this health technology policy assessment was to determine the effectiveness of spinal cord stimulation (SCS) to manage chronic intractable neuropathic pain and to evaluate the adverse events and Ontario-specific economic profile of this technology.
Clinical Need
SCS is a reversible pain therapy that uses low-voltage electrical pulses to manage chronic, intractable neuropathic pain of the trunk or limbs. Neuropathic pain begins or is caused by damage or dysfunction to the nervous system and can be difficult to manage.
The prevalence of neuropathic pain has been estimated at about 1.5% of the population in the United States and 1% of the population in the United Kingdom. These prevalence rates are generalizable to Canada.
Neuropathic pain is extremely difficult to manage. People with symptoms that persist for at least 6 months or who have symptoms that last longer than expected for tissue healing or resolution of an underlying disease are considered to have chronic pain. Chronic pain is an emotional, social, and economic burden for those living with it. Depression, reduced quality of life (QOL), absenteeism from work, and a lower household income are positively correlated with chronic pain.
Although the actual number is unknown, a proportion of people with chronic neuropathic pain fail to obtain pain relief from pharmacological therapies despite adequate and reasonable efforts to use them. These people are said to have intractable neuropathic pain, and they are the target population for SCS.
The most common indication for SCS in North America is chronic intractable neuropathic pain due to failed back surgery syndrome (FBSS), a term that describes persistent leg or back and leg pain in patients who have had back or spine surgery. Neuropathic pain due to complex regional pain syndrome (CRPS), which can develop in the distal aspect of a limb a minor injury, is another common indication. To a lesser extent, chronic intractable pain of postherpetic neuralgia, which is a persistent burning pain and hyperesthesia along the distribution of a cutaneous nerve after an attack of herpes zoster, is also managed with SCS.
For each condition, SCS is considered as a pain management therapy only after conventional pain therapies, including pharmacological, nonpharmacological, and surgical treatments, if applicable, have been attempted and have failed.
The Technology
The SCS technology consists of 3 implantable components: a pulse generator, an extension cable, and a lead (a small wire). The pulse generator is the power source for the spinal cord stimulator. It generates low-voltage electrical pulses. The extension cable connects the pulse generator to the lead. The lead is a small, insulated wire that has a set of electrodes at one end. The lead is placed into the epidural space on the posterior aspect of the spinal cord, and the electrodes are positioned at the level of the nerve roots innervating the painful area. An electrical current from the electrodes induces a paresthesia, or a tingling sensation that masks the pain.
Before SCS is initiated, candidates must have psychological testing to rule out major psychological illness, drug habituation, and issues of secondary gain that can negatively influence the success of the therapy. Successful candidates will have a SCS test stimulation period (trial period) to assess their responsiveness to SCS. The test stimulation takes about 1 week to complete, and candidates who obtain at least 50% pain relief during this period are deemed suitable to receive a permanent implantation of a spinal cord stimulator
Review Strategy
The Medical Advisory Secretariat (MAS) reviewed all published health technology assessments of spinal cord stimulation. Following this, a literature search was conducted from 2000 to January, 2005 and a systematic review of the literature was completed. The primary outcome for the systematic review was pain relief. Secondary outcomes included functional status and quality of life. After applying the predetermined inclusion and exclusion criteria, 2 randomized controlled trials (MAS level 2 evidence), and 2 prospective non-randomized controlled trials with a before-and-after-treatment study design (MAS level 3a evidence) were retrieved and reviewed.
Summary of Findings
The authors of 6 health technology assessments concluded that evidence exists to support the effectiveness of SCS to decrease pain in various neuropathic pain syndromes. However, the quality of this evidence varied among reports from weak to moderate.
The systematic review completed by MAS found high quality level 2 evidence that SCS decreases pain and level 3a evidence that it improves functional status and quality of life in some people with neuropathic pain conditions. The rate of technical failures was approximately 11%, which included electrode lead migration and/or malposition. Procedural complications included infection and dural puncture; each occurred at a rate of 1.2%.
Conclusions
SCS may be considered for patients with chronic, neuropathic pain for whom standard pain treatments have failed and when there is no indication for surgical intervention to treat the underlying condition.
PMCID: PMC3382299  PMID: 23074473
16.  Anterior Spinal Artery Syndrome in a Girl With Down Syndrome: Case Report and Literature Review 
Background/Objective:
Anterior spinal artery syndrome is an extremely rare cause of acute ischemic cord infarction in children. It is caused by hypoperfusion of the anterior spinal artery, leading to ischemia in the anterior two thirds of the spinal cord. The presentation is usually with an acute and painful myelopathy with impaired bladder and bowel control. Pain and temperature sensation below the lesion are lost, whereas vibration and position sense is intact because of the preservation of the posterior columns.
Methods:
Case report.
Results:
A 16-year-old girl with Down syndrome presented with urinary retention and acute complete flaccid paralysis of the legs with absent deep tendon and abdominal reflexes. Magnetic resonance imaging showed a signal abnormality in the anterior half of the thoracic cord from T5 to T12, consistent with anterior spinal artery infarction.
Conclusions:
Pediatricians should consider anterior spinal artery syndrome in the child who presents with acute, painful myelopathy. We summarize the etiology, neurological findings and outcomes of 19 children found in the literature with anterior spinal artery syndrome.
PMCID: PMC2718815  PMID: 19810637
Anterior spinal artery syndrome; Myelopathy, acute; Spinal cord infarction; Down syndrome; Rehabilitation; Paralysis; Spasticity
17.  Image-guided facet joint injection 
Chronic spine pain poses a peculiar diagnostic and therapeutic challenge due to multiple pain sources, overlapping clinical features and nonspecific radiological findings. Facet joint injection is an interventional pain management tool for facet-related spinal pain that can be effectively administered by a radiologist. This technique is the gold standard for identifying facet joints as the source of spinal pain. The major indications for facet injections include strong clinical suspicion of the facet syndrome, focal tenderness over the facet joints, low back pain with normal radiological findings, post-laminectomy syndrome with no evidence of arachnoiditis or recurrent disc disease, and persistent low back pain after spinal fusion. The contraindications are more ancillary, with none being absolute. Like any synovial joint degeneration, inflammation and injury can lead to pain on motion, initiating a vicious cycle of physical deconditioning, irritation of facet innervations and muscle spasm. Image-guided injection of local anesthetic and steroid into or around the facet joint aims to break this vicious cycle and thereby provide pain relief. This outpatient procedure has high diagnostic accuracy, safety and reproducibility but the therapeutic outcome is variable.
doi:10.2349/biij.7.1.e4
PMCID: PMC3107686  PMID: 21655113
Facet syndrome; intra-articular facet injection; imaging-guided injections; interventional spinal procedures; low back pain; spinal pain
18.  Principles of management of osteometabolic disorders affecting the aging spine 
European Spine Journal  2003;12(Suppl 2):S113-S131.
Osteoporosis is the most common contributing factor of spinal fractures, which characteristically are not generally known to produce spinal cord compression symptoms. Recently, an increasing number of medical reports have implicated osteoporotic fractures as a cause of serious neurological deficit and painful disabling spinal deformities. This has been corroborated by the present authors as well. These complications are only amenable to surgical management, requiring instrumentation. Instrumenting an osteoporotic spine, although a challenging task, can be accomplished if certain guidelines for surgical techniques are respected. Neurological deficits respond equally well to an anterior or posterior decompression, provided this is coupled with multisegmental fixation of the construct. With the steady increase in the elderly population, it is anticipated that the spine surgeon will face serious complications of osteoporotic spines more frequently. With regard to surgery, however, excellent correction of deformities can be achieved, by combining anterior and posterior approaches. Paget's disease of bone (PD) is a non-hormonal osteometabolic disorder and the spine is the second most commonly affected site. About one-third of patients with spinal involvement exhibit symptoms of clinical stenosis. In only 12–24% of patients with PD of the spine is back pain attributed solely to PD, while in the majority of patients, back pain is either arthritic in nature or a combination of a pagetic process and coexisting arthritis. In this context, one must be certain before attributing low back pain to PD exclusively, and antipagetic medical treatment alone may be ineffective. Neural element dysfunction may be attributed to compressive myelopathy by pagetic bone overgrowth, pagetic intraspinal soft tissue overgrowth, ossification of epidural fat, platybasia, spontaneous bleeding, sarcomatous degeneration and vertebral fracture or subluxation. Neural dysfunction can also result from spinal ischemia when blood is diverted by the so-called "arterial steal syndrome". Because the effectiveness of pharmacologic treatment for pagetic spinal stenosis has been clearly demonstrated, surgical decompression should only be instituted after failure of antipagetic medical treatment. Surgery is indicated as a primary treatment when neural compression is secondary to pathologic fractures, dislocations, spontaneous epidural hematoma, syringomyelia, platybasia, or sarcomatous transformation. Five classes of drugs are available for the treatment of PD. Bisphosphonates are the most popular antipagetic drug and several forms have been investigated.
doi:10.1007/s00586-003-0600-5
PMCID: PMC3591829  PMID: 14505119
Osteoporosis; Fractures; Neurological deficit; Deformity; Paget's disease; Back pain; Spinal stenosis; Myelopathy; Treatment
19.  Paget's Disease of the spine and its management 
European Spine Journal  2001;10(5):370-384.
Abstract.
A review of the literature was conducted to study the pathomechanics by which Paget's Disease of bone (PD) alters the spinal structures that result in distinct spinal pathologic entities such as pagetic spinal arthritis, spinal stenosis, and other pathologies, and to assess the best treatment options and available drugs. The spine is the second most commonly affected site with PD. About one-third of patients with spinal involvement exhibit symptoms of clinical stenosis. In only 12–24% of patients with PD of the spine is back pain attributed solely to PD, while in the majority of patients back pain is either arthritic in nature or a combination of a pagetic process and coexisting arthritis. Neural element dysfunction may be attributed to compressive myelopathy by pagetic bone overgrowth, pagetic intraspinal soft tissue overgrowth, ossification of epidural fat, platybasia, spontaneous bleeding, sarcomatous degeneration and vertebral fracture or subluxation. Neural dysfunction can also result from spinal ischemia, when blood is diverted by the so-called ''arterial steal syndrome''. Because the effectiveness of pharmacologic treatment for pagetic spinal stenosis has been clearly demonstrated, surgical decompression should only be instituted after failure of antipagetic medical treatment. Surgery is indicated as a primary treatment when neural compression is secondary to pathologic fractures, dislocations, spontaneous epidural hematoma, syringomyelia, platybasia, or sarcomatous transformation. Since, in the majority of cases with pagetic spinal involvement, there are also coexisting osteoarthritic changes, antipagetic medical treatment alone may be disappointing. Therefore, one must be careful before attributing low back pain to PD alone. Five classes of drugs are available for the treatment of PD: bisphosphonates, calcitonins, mithramycin (plicamycin), gallium nitrate, and ipriflavone. Bisphosphonates are the most popular, and several forms have been investigated, but only the following forms have been approved for clinical use: disodium etidronate, clodronate, aledronate, risedronate, neridronate, pamidronate, tiludronate, ibadronate, aminohydroxylbutylidene bisphosphonate, olpadronate, and zoledronate. Several of these forms are still under investigation.
doi:10.1007/s005860100329
PMCID: PMC3611523  PMID: 11718191
Paget's Disease Back pain Spinal stenosis Myelopathy Complications Medical treatment Surgery Review
20.  Scalene Myofascial Pain Syndrome Mimicking Cervical Disc Prolapse: A Report of Two Cases 
Scalene myofascial pain syndrome is a regional pain syndrome wherein pain originates over the neck area and radiates down to the arm. This condition may present as primary or secondary to underlying cervical pathology. Although scalene myofascial pain syndrome is a well known medical entity, it is often misdiagnosed as being some other neck pain associated with radiculopathy, such as cervical disc prolapse, cervical spinal stenosis and thoracic outlet syndrome. Because scalene myofascial pain syndrome mimics cervical radiculopathy, this condition often leads to mismanagement, which can, in turn, result in persistent pain and suffering. In the worst-case scenarios, patients may be subjected to unjustifiable surgical intervention. Because the clinical findings in scalene myofascial pain syndrome are “pathognomonic”, clinicians should be aware of ways to recognize this disorder and be able to differentiate it from other conditions that present with neck pain and rediculopathy. We present two cases of unilateral scalene myofascial pain syndrome that significantly impaired the patients’ functioning and quality of life. This case report serves to create awareness about the existence of the syndrome and to highlight the potential morbidity due to clinical misdiagnosis.
PMCID: PMC3216145  PMID: 22135529
cervical radiculopathy; myofascial pain syndrome; pain radiation; Scalene muscle; trigger point; neurosciences
21.  Artificial Discs for Lumbar and Cervical Degenerative Disc Disease –Update 
Executive Summary
Objective
To assess the safety and efficacy of artificial disc replacement (ADR) technology for degenerative disc disease (DDD).
Clinical Need
Degenerative disc disease is the term used to describe the deterioration of 1 or more intervertebral discs of the spine. The prevalence of DDD is roughly described in proportion to age such that 40% of people aged 40 years have DDD, increasing to 80% among those aged 80 years or older. Low back pain is a common symptom of lumbar DDD; neck and arm pain are common symptoms of cervical DDD. Nonsurgical treatments can be used to relieve pain and minimize disability associated with DDD. However, it is estimated that about 10% to 20% of people with lumbar DDD and up to 30% with cervical DDD will be unresponsive to nonsurgical treatments. In these cases, surgical treatment is considered. Spinal fusion (arthrodesis) is the process of fusing or joining 2 bones and is considered the surgical gold standard for DDD.
Artificial disc replacement is the replacement of the degenerated intervertebral disc with an artificial disc in people with DDD of the lumbar or cervical spine that has been unresponsive to nonsurgical treatments for at least 6 months. Unlike spinal fusion, ADR preserves movement of the spine, which is thought to reduce or prevent the development of adjacent segment degeneration. Additionally, a bone graft is not required for ADR, and this alleviates complications, including bone graft donor site pain and pseudoarthrosis. It is estimated that about 5% of patients who require surgery for DDD will be candidates for ADR.
Review Strategy
The Medical Advisory Secretariat conducted a computerized search of the literature published between 2003 and September 2005 to answer the following questions:
What is the effectiveness of ADR in people with DDD of the lumbar or cervical regions of the spine compared with spinal fusion surgery?
Does an artificial disc reduce the incidence of adjacent segment degeneration (ASD) compared with spinal fusion?
What is the rate of major complications (device failure, reoperation) with artificial discs compared with surgical spinal fusion?
One reviewer evaluated the internal validity of the primary studies using the criteria outlined in the Cochrane Musculoskeletal Injuries Group Quality Assessment Tool. The quality of concealment allocation was rated as: A, clearly yes; B, unclear; or C, clearly no. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to evaluate the overall quality of the body of evidence (defined as 1 or more studies) supporting the research questions explored in this systematic review. A random effects model meta-analysis was conducted when data were available from 2 or more randomized controlled trials (RCTs) and when there was no statistical and or clinical heterogeneity among studies. Bayesian analyses were undertaken to do the following:
Examine the influence of missing data on clinical success rates;
Compute the probability that artificial discs were superior to spinal fusion (on the basis of clinical success rates);
Examine whether the results were sensitive to the choice of noninferiority margin.
Summary of Findings
The literature search yielded 140 citations. Of these, 1 Cochrane systematic review, 1 RCT, and 10 case series were included in this review. Unpublished data from an RCT reported in the grey literature were obtained from the manufacturer of the device. The search also yielded 8 health technology assessments evaluating ADR that are also included in this review.
Six of the 8 health technology assessments concluded that there is insufficient evidence to support the use of either lumbar or cervical ADR. The results of the remaining 2 assessments (one each for lumbar and cervical ADR) led to a National Institute for Clinical Excellence guidance document supporting the safety and effectiveness of lumbar and cervical ADR with the proviso that an ongoing audit of all clinical outcomes be undertaken owing to a lack of long-term outcome data from clinical trials.
Regarding lumbar ADR, data were available from 2 noninferiority RCTs to complete a meta-analysis. The following clinical, health systems, and adverse event outcome measures were synthesized: primary outcome of clinical success, Oswestry Disability Index (ODI) scores, pain VAS scores, patient satisfaction, duration of surgery, amount of blood loss, length of hospital stay, rate of device failure, and rate of reoperation.
The meta-analysis of overall clinical success supported the noninferiority of lumbar ADR compared with spinal fusion at 24-month follow-up. Of the remaining clinical outcome measures (ODI, pain VAS scores, SF-36 scores [mental and physical components], patient satisfaction, and return to work status), only patient satisfaction and scores on the physical component scale of the SF-36 questionnaire were significantly improved in favour of lumbar ADR compared with spinal fusion at 24 months follow-up. Blood loss and surgical time showed statistical heterogeneity; therefore, meta-analysis results are not interpretable. Length of hospital stay was significantly shorter in patients receiving the ADR compared with controls. Neither the number of device failures nor the number of neurological complications at 24 months was statistically significantly different between the ADR and fusion treatment groups. However, there was a trend towards fewer neurological complications at 24 months in the ADR treatment group compared with the spinal fusion treatment group.
Results of the Bayesian analyses indicated that the influence of missing data on the outcome measure of clinical success was minimal. The Bayesian model indicated that the probability for ADR being better than spinal fusion was 79%. The probability of ADR being noninferior to spinal fusion using a -10% noninferiority bound was 92%, and using a -15% noninferiority bound was 94%. The probability of artificial discs being superior to spinal fusion in a future trial was 73%.
Six case series were reviewed, mainly to characterize the rate of major complications for lumbar ADR. The Medical Advisory Secretariat defined a major complication as any reoperation; device failure necessitating a revision, removal or reoperation; or life-threatening event. The rates of major complications ranged from 0% to 13% per device implanted. Only 1 study reported the rate of ASD, which was detected in 2 (2%) of the 100 people 11 years after surgery.
There were no RCT data available for cervical ADR; therefore, data from 4 case series were reviewed for evidence of effectiveness and safety. Because data were sparse, the effectiveness of cervical ADR compared with spinal fusion cannot be determined at this time.
The rate of major complications was assessed up to 2 years after surgery. It was found to range from 0% to 8.1% per device implanted. The rate of ASD is not reported in the clinical trial literature.
The total cost of a lumbar ADR procedure is $15,371 (Cdn; including costs related to the device, physician, and procedure). The total cost of a lumbar fusion surgery procedure is $11,311 (Cdn; including physicians’ and procedural costs).
Conclusions
Lumbar Artificial Disc Replacement
Since the 2004 Medical Advisory Secretariat health technology policy assessment, data from 2 RCTs and 6 case series assessing the effectiveness and adverse events profile of lumbar ADR to treat DDD has become available. The GRADE quality of this evidence is moderate for effectiveness and for short-term (2-year follow-up) complications; it is very low for ASD.
The effectiveness of lumbar ADR is not inferior to that of spinal fusion for the treatment of lumbar DDD. The rates for device failure and neurological complications 2 years after surgery did not differ between ADR and fusion patients. Based on a Bayesian meta-analysis, lumbar ADR is 79% superior to lumbar spinal fusion.
The rate of major complications after lumbar ADR is between 0% and 13% per device implanted. The rate of ASD in 1 case series was 2% over an 11-year follow-up period.
Outcome data for lumbar ADR beyond a 2-year follow-up are not yet available.
Cervical Artificial Disc Replacement
Since the 2004 Medical Advisory Secretariat health technology policy assessment, 4 case series have been added to the body of evidence assessing the effectiveness and adverse events profile of cervical ADR to treat DDD. The GRADE quality of this evidence is very low for effectiveness as well as for the adverse events profile. Sparse outcome data are available.
Because data are sparse, the effectiveness of cervical ADR compared with spinal fusion cannot be determined at this time.
The rate of major complications was assessed up to 2 years after surgery; it ranged from 0% to 8.1% per device implanted. The rate of ASD is not reported in the clinical trial literature.
PMCID: PMC3379529  PMID: 23074480
22.  Fibromyalgia and arachnoiditis presented as an acute spinal disorder 
Background:
Adhesive arachnoiditis is a chronic, insidious condition that causes debilitating intractable pain and a range of other neurological problems. Its pathophysiology is not well understood. This manuscript discusses its presentations, which can mimic an acute spinal disorder, its hypothetical pathophysiology, treatment, and its relationship with fibromyalgia.
Case Description:
The authors present a case of a 47-year-old female who presented with clinical features mimicking an acute spinal disorder but later found to have an adhesive arachnoiditis. She was admitted following a trauma with complaints of back pain and paraplegia. On examination, there was marked tenderness over thoracolumbar spine with lower limbs upper motor neuron weakness. An urgent magnetic resonance imaging (MRI) of the spine revealed multiple lesions at her thoracic and lumbar spinal canals, which did not compress the spinal cord. Therefore, conservative management was initiated. Despite on regular therapies, her back and body pain worsened and little improvement in her limbs power was noted. Laminectomy was pursued and found to have spinal cord arachnoiditis. Subsequently, she was operated by other team members for multiple pelvic masses, which later proved to be benign. After gathering all the clinical information obtained at surgery and after taking detailed history inclusive of cognitive functions, diagnosis of an adhesive arachnoiditis syndrome was made. Currently, she is managed by neuropsychologist and pain specialist.
Conclusion:
This case report highlights the importance of knowing an adhesive arachnoiditis syndrome – a rarely discussed pathology by the neurosurgeon, which discloses a significant relationship between immune and nervous systems.
doi:10.4103/2152-7806.143364
PMCID: PMC4228496  PMID: 25396073
Arachnoiditis; autoimmune disease; fibromyalgia; greater limbic system; spinal disorder; spinal trauma
23.  The diagnosis and management of synovial cysts: Efficacy of surgery versus cyst aspiration 
Surgical Neurology International  2012;3(Suppl 3):S157-S166.
Background:
The surgical management of lumbar synovial cysts that have extruded into the spinal canal remains controversial (e.g. decompression with/without fusion).
Methods:
The neurological presentation, anatomy, pathophysiology, and surgical challenges posed by synovial cysts in the lumbar spine are well known. Neurological complaints typically include unilateral or, more rarely, bilateral radicular complaints, and/or cauda equina syndromes. Anatomically, synovial cysts constitute cystic dilatations of synovial sheaths that directly extrude from facet joints into the spinal canal. Pathophysiologically, these cysts reflect disruption of the facet joints often with accompanying instability, and potentially compromise both the cephalad and caudad nerve roots.
Results:
Aspiration of lumbar synovial cysts, which are typically gelatinous and non-aspirable, and typically performed by “pain specialists” (e.g. pain management, rehabilitation, radiologists, others) utilizing fluoroscopy or CT-guided aspiration, is associated with 50–100% failure rates. Surgical decompression with/without fusion (as the issue regarding fusion remains unsettled) results in the resolution of back and radicular pain in 91.6–92.5% and 91.1–91.9% of cases, respectively.
Conclusions:
After a thorough review of the literature, it appears that the treatment with the best outcome for patients with synovial cysts is cyst removal utilizing surgical decompression; the need for attendant fusion remains unsettled. The use of an alternative treatment, percutaneous aspiration of cysts, appears to have a much higher recurrence and failure rate, but may be followed by surgery if warranted.
doi:10.4103/2152-7806.98576
PMCID: PMC3422091  PMID: 22905322
Decompression; extruded lumbar synovial cysts; failed aspiration; failed techniques; fusion
24.  Multi-target neurostimulation for adequate long-term relief of neuropathic and nociceptive chronic pain components 
Surgical Neurology International  2013;4(Suppl 3):S170-S175.
Successful treatment of chronic pain for patients with failed back surgery syndrome can be extremely complicated. These patients require careful and individualized clinical assessment, as they often present with mixed pain syndromes that involve both neuropathic and nociceptive components. The distinct types of pain involved in such cases may require combined treatments from individual interventions that are analgesically independent and specific for each type of pain involved. Neuromodulation by electric stimulation at appropriately chosen targets and combinations may be an important option to consider for such patients. We present a case of combined debilitating axial nociceptive spinal pain and bilateral neuropathic leg pain in a patient after 14 failed back operations. A combination of spinal cord stimulation (SCS) and deep brain stimulation in the periventricular gray (PVG) have successfully provided the patient with complete relief of both components of his chronic pain condition, after all other pain management options had been exhausted. By alternating activation of each implanted stimulator separately and in conjunction, we were able to demonstrate a clinically independent analgesic character for each stimulation system, each specific to a particular type of pain. The SCS provided complete relief of the neuropathic pain component, without affecting the nociceptive component at all. The PVG stimulation provided complete relief of the nociceptive component, without affecting the neuropathic component at all. In combination, there was complete relief of the total chronic pain condition. There appeared to be no overlapping or synergistic effect between the two neuromodulation systems in the patient. The patient has had prolonged complete relief from his chronic pain condition with the combined neuromodulation intervention over 22 years of follow-up.
doi:10.4103/2152-7806.110676
PMCID: PMC3654775  PMID: 23682344
Chronic pain; deep brain stimulation; failed back surgery syndrome; periventricular gray; spinal cord stimulation
25.  Self-injurious behaviour in intellectual disability syndromes: evidence for aberrant pain signalling as a contributing factor 
Background
In most individuals, injury results in activation of peripheral nociceptors (pain-sensing neurons of the peripheral nervous system) and amplification of central nervous system (CNS) pain pathways that serve as a disincentive to continue harmful behaviour; however, this may not be the case in some developmental disorders that cause intellectual disability (ID). Moreover, individuals affected by ID disorders may initiate self-injurious behaviour to address irritating or painful sensations. In normal individuals, a negative feedback loop decreases sensation of pain, which involves descending inhibitory neurons in the CNS that attenuate spinal nociceptive processing. If spinal nociceptive signalling is impaired in these developmental disorders, an exaggerated painful stimulus may be required in order to engage descending anti-nociceptive signals.
Methods
Using electronic databases, we conducted a review of publications regarding the incidence of chronic pain or altered pain sensation in ID patients or corresponding preclinical models.
Results
There is a body of evidence indicating that individuals with fragile X mental retardation and/or Rett syndrome have altered pain sensation. These findings in humans are supported by mechanistic studies using genetically modified mice harbouring mutations consistent with the human disease. Thus, once self-injurious behaviour is initiated, the signal to stop may be missing. Several developmental disorders that cause ID are associated with increased incidence of gastroesophageal reflux disease (GERD), which can cause severe visceral pain. Individuals affected by these disorders who also have GERD may self-injure as a mechanism to engage descending inhibitory circuits to quell visceral pain. In keeping with this hypothesis, pharmacological treatment of GERD has been shown to be effective for reducing self-injurious behaviour in some patients. Hence, multiple lines of evidence suggest aberrant nociceptive processing in developmental disorders that cause ID.
Conclusions
There is evidence that pain pathways and pain amplification mechanisms are altered in several preclinical models of developmental disorders that cause ID. We present hypotheses regarding how impaired pain pathways or chronic pain might contribute to self-injurious behaviour. Studies evaluating the relationship between pain and self-injurious behaviour will provide better understanding of the mechanisms underlying self-injurious behaviour in the ID population and may lead to more effective treatments.
doi:10.1111/j.1365-2788.2011.01484.x
PMCID: PMC3272540  PMID: 21917053
central sensitization; diffuse noxious inhibitory control; fragile X; pain; Rett syndrome; self-injury

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