Background Years after a traumatic spinal cord injury (SCI), a subset of patients may develop progressive clinical deterioration due to intradural scar formation and spinal cord tethering, with or without an associated syringomyelia. Meningitis, intradural hemorrhages, or intradural tumor surgery may also trigger glial scar formation and spinal cord tethering, leading to neurological worsening. Surgery is the treatment of choice in these chronic SCI patients. Objective We hypothesized that cerebrospinal fluid (CSF) and plasma biomarkers could track ongoing neuronal loss and scar formation in patients with spinal cord tethering and are associated with clinical symptoms. Methods We prospectively enrolled 12 patients with spinal cord tethering and measured glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCH-L1), and phosphorylated Neurofilament-heavy (pNF-H) in CSF and blood. Seven patients with benign lumbar intradural tumors and 7 patients with cervical radiculopathy without spinal cord involvement served as controls. Results All evaluated biomarker levels were markedly higher in CSF than in plasma, without any correlation between the two compartments. When compared with radiculopathy controls, CSF GFAP and pNF-H levels were higher in patients with spinal cord tethering ( p ≤ 0.05). In contrast, CSF UCH-L1 levels were not altered in chronic SCI patients when compared with either control groups. Conclusions The present findings suggest that in patients with spinal cord tethering, CSF GFAP and pNF-H levels might reflect ongoing scar formation and neuronal injury potentially responsible for progressive neurological deterioration.

BACKGROUND:Intrathecal baclofen (ITB) treatment is considered a powerful tool in the management of severe spasticity in neurological conditions such as multiple sclerosis, cerebral palsy, and traumatic spinal cord and brain injury.OBJECTIVES:The objective of this study was to assess the effectiveness of the ITB in patients with inherited ataxia suffering from severe painful spasms and/or spasticity.METHOD:A total of 5 patients with spinocerebellar ataxia 3 or 7 or Friedreich's ataxia were included in this observational multicenter study. The patients were interviewed and completed outcome measures assessing pain (The Brief Pain Inventory), fatigue (Fatigue Severity Scale), and life satisfaction (LiSAT-9) before and 1 year after the treatment. Spasticity (Modified Ashworth Scale) and spasm frequency (SPFS) were measured objectively for each patient.RESULTS:The mean treatment time was 1.9 years. Evaluation of established standard forms revealed symptomatic relief from spasticity, spasms, pain, and fatigue in addition to improved body posture, sleep, and life satisfaction after ITB treatment.CONCLUSIONS:We report the potential beneficial effects of ITB treatment in patients with inherited ataxia who also suffer from spasticity/spasms. ITB treatment indication in neurological disorders allows for extension to the treatment of spasticity/ spasms in patients with hereditary ataxia.

Study design Retrospective data collection and patient-reported outcome measures. Objectives To investigate surgical outcome, complications, and patient satisfaction in patients with chronic SCI and symptomatic post-traumatic progressive myelopathy (PPM) who underwent neurosurgical untethering and/or spinal cord cyst drainage with the aim of preventing further neurological deterioration. Setting Single-center study at an academic neurosurgery department. Methods All SCI patients who underwent neurosurgery between 1996 and 2013 were retrospectively included. All medical charts and the treating surgeon’s operative reports were reviewed to identify surgical indications, surgical technique, and post-operative complications. A questionnaire and an EQ-5D-instrument were used to assess patient's self-described health status and satisfaction at long-term follow-up. Results Fifty-two patients (43 men, 9 women) were identified, of whom five were dead and one was lost to follow-up. Main indications for surgery were pain (54%), motor (37%), or sensory (8%) impairment, and spasticity (2.0%). Overall complications were rare (8%). At follow-up, the subjectively perceived outcome was improved in 24 and remained unchanged in 21 patients. Thus, the surgical aim was met in 87% of patients. Of the 46 eligible patients, 38 responded to the questionnaire of whom 65% were satisfied with the surgical results. Patients with cervical lesions were more satisfied with the surgical treatment than patients with thoracic/thoracolumbar lesions ( p = 0.05). Conclusions Neurosurgical untethering and/or cyst drainage in chronic SCI patients and PPM resulted in a high degree of patient satisfaction, particularly in cervical SCI patients with minimal complications.

BackgroundThe optimal treatment of symptomatic perineural (Tarlov) cysts is controversial. Numerous surgical techniques have been proposed with conflicting results. A series of Tarlov cysts treated with a novel surgical approach is presented.MethodsPatients with surgically treated symptomatic perineural cysts during 2013-2016 were included. The main indications for surgery were persistent radicular symptoms, pelvic pain, urinary and/ or bowel disturbances. At surgery, the cyst was opened and fenestrated. The cyst wall was then closed with packing, fibrin glue and a pedicled vascularized fasciocutaneous flap rotated into the area for obliteration of the dead space. Patients were followed-up with clinical visits and repeat magnetic resonance imaging (MRI) scans.ResultsSeven consecutive patients were included. The mean age was 50.3 years (range, 25-80 years) and the mean duration of symptoms was 49.3 months (range, 3-130 months). With one exception, all patients had urine and/or bowel problems (incontinence) preoperatively. A lumbar drain was inserted in five patients. The mean follow-up period was 15.4 months. Symptoms improved in 4/7 patients, in two cases no clinical difference was noted while one patient deteriorated. In two cases, a spinal cord stimulator was eventually implanted. In all seven cases, a significantly decreased cyst size was noted on MRI.ConclusionsCyst fenestration and the use of a vascularized fasciocutaneous flap successfully obliterated all cysts, with satisfactory clinical efficacy. Larger and comparative studies are warranted to clarify the long-term effects of this surgical technique in patients with symptomatic Tarlov cysts.

OBJECTIVE The aim of this study was to evaluate the 5- to 8-year outcome of anterior cervical decompression and fusion (ACDF) combined with a structured physiotherapy program as compared with that following the same physiotherapy program alone in patients with cervical radiculopathy. No previous prospective randomized studies with a follow-up of more than 2 years have compared outcomes of surgical versus nonsurgical intervention for cervical radiculopathy. METHODS Fifty-nine patients were randomized to ACDF surgery with postoperative physiotherapy (30 patients) or to structured physiotherapy alone (29 patients). The physiotherapy program included general and specific exercises as well as pain coping strategies. Outcome measures included neck disability (Neck Disability Index [NDI]), neck and arm pain intensity (visual analog scale [VAS]), health state (EQ-5D questionnaire), and a patient global assessment. Patients were followed up for 5-8 years. RESULTS After 5-8 years, the NDI was reduced by a mean score% of 21 (95% CI 14-28) in the surgical group and 11% (95% CI 4%-18%) in the nonsurgical group (p = 0.03). Neck pain was reduced by a mean score of 39 mm (95% CI 26-53 mm) compared with 19 mm (95% CI 7-30 mm; p = 0.01), and arm pain was reduced by a mean score of 33 mm (95% CI 18-49 mm) compared with 19 mm (95% CI 7-32 mm; p = 0.1), respectively. The EQ-5D had a mean respective increase of 0.29 (95% CI 0.13-0.45) compared with 0.14 (95% CI 0.01-0.27; p = 0.12). Ninety-three percent of patients in the surgical group rated their symptoms as "better" or "much better" compared with 62% in the nonsurgical group (p = 0.005). Both treatment groups experienced significant improvement over baseline for all outcome measures. CONCLUSIONS In this prospective randomized study of 5- to 8-year outcomes of surgical versus nonsurgical treatment in patients with cervical radiculopathy, ACDF combined with physiotherapy reduced neck disability and neck pain more effectively than physiotherapy alone. Self-rating by patients as regards treatment outcome was also superior in the surgery group. No significant differences were seen between the 2 patient groups as regards arm pain and health outcome.

Markus Engquist, Håkan Löfgren, Birgitta Öberg, Anders Holtz, Anneli Peolsson, Anne Söderlund, Ludek Vavruch and Bengt Lind, Surgery Versus Non-Surgical Treatment for Cervical Radiculopathy: A prospective, randomized study comparing surgery plus physiotherapy with physiotherapy alone with a two year follow-up, 2013, Spine, (38), 20, 17151722. http://dx.doi.org/10.1097/BRS.0b013e31829ff095 Copyright: Lippincott, Williams & Wilkins http://www.lww.com/

STUDY DESIGN:Prospective randomized controlled trial.OBJECTIVE:To analyze factors that may influence the outcome of anterior cervical decompression and fusion (ACDF) followed by physiotherapy versus physiotherapy alone for treatment of patients with cervical radiculopathy.SUMMARY OF BACKGROUND DATA:An understanding of patient-related factors affecting the outcome of ACDF is important for preoperative patient selection. No previous prospective, randomized study of treatment effect modifiers relating to outcome of ACDF compared with physiotherapy has been carried out.METHODS:60 patients with cervical radiculopathy were randomized to ACDF followed by physiotherapy or physiotherapy alone. Data for possible modifiers of treatment outcome at 1 year, such as sex, age, duration of pain, pain intensity, disability (Neck Disability Index, NDI), patient expectations of treatment, anxiety due to neck/arm pain, distress (Distress and Risk Assessment Method), self-efficacy (Self-Efficacy Scale) health status (EQ-5D), and magnetic resonance imaging findings were collected. A multivariate analysis was performed to find treatment effect modifiers affecting the outcome regarding arm/neck pain intensity and NDI.RESULTS:Factors that significantly altered the treatment effect between treatment groups in favor of surgery were: duration of neck pain less than 12 months (P = 0.007), duration of arm pain less than 12 months (P = 0.01) and female sex (P = 0.007) (outcome: arm pain), low EQ-5D index (outcome: neck pain, P = 0.02), high levels of anxiety due to neck/arm pain (outcome: neck pain, P = 0.02 and NDI, P = 0.02), low Self-Efficacy Scale score (P = 0.05), and high Distress and Risk Assessment Method score (P = 0.04) (outcome: NDI). No factors were found to be associated with better outcome with physiotherapy alone.CONCLUSION:In this prospective, randomized study of patients with cervical radiculopathy, short duration of pain, female sex, low health quality, high levels of anxiety due to neck/arm pain, low self-efficacy, and a high level of distress before treatment were associated with better outcome from surgery. No factors were found to be associated with better outcome from physiotherapy alone.

STUDY DESIGN:Prospective randomized study. OBJECTIVE:To investigate differences in physical functional outcome in patients with radiculopathy due to cervical disc disease, after structured physiotherapy alone (consisting of neck-specific exercises with a cognitive-behavioral approach) versus after anterior cervical decompression and fusion (ACDF) followed by the same structured physiotherapy program. SUMMARY OF BACKGROUND DATA:No earlier studies have evaluated the effectiveness of a structured physiotherapy program or postoperative physical rehabilitation after ACDF for patients with magnetic resonance imaging-verified nerve compression due to cervical disc disease. METHODS:Our prospective randomized study included 63 patients with radiculopathy and magnetic resonance imaging-verified nerve root compression, who were randomized to receive either ACDF in combination with physiotherapy or physiotherapy alone. For 49 of these patients, an independent examiner measured functional outcomes, including active range of neck motion, neck muscle endurance, and hand-related functioning before treatment and at 3-, 6-, 12-, and 24-month follow-ups. RESULTS:There were no significant differences between the 2 treatment alternatives in any of the measurements performed (P = 0.17-0.91). Both groups showed improvements over time in neck muscle endurance (P ≤ 0.01), manual dexterity (P ≤ 0.03), and right-handgrip strength (P = 0.01). CONCLUSION:Compared with a structured physiotherapy program alone, ACDF followed by physiotherapy did not result in additional improvements in neck active range of motion, neck muscle endurance, or hand-related function in patients with radiculopathy. We suggest that a structured physiotherapy program should precede a decision for ACDF intervention in patients with radiculopathy, to reduce the need for surgery. LEVEL OF EVIDENCE:2.

Study Design. Prospective randomized controlled trial. Objective. To study the outcome of anterior cervical decompression and fusion combined with a structured physiotherapy program compared with the same physiotherapy program alone for patients with cervical radiculopathy. Summary of Background Data. Knowledge concerning the effects of interventions for patients with cervical radiculopathy is scarce due to a lack of randomized studies. Methods. Sixty-three patients were randomized to surgery with postoperative physiotherapy (n = 31) or physiotherapy alone (n = 32). The surgical group was treated with anterior cervical decompression and fusion. The physiotherapy program included general/specific exercises and pain-coping strategies. The outcome measures were disability (Neck Disability Index), neck and arm pain intensity (visual analogue scale), and the patient's global assessment. Patients were followed for 24 months. Results. The result from the repeated-measures analysis of variance showed no significant between-group difference for Neck Disability Index (P = 0.23). For neck pain intensity, the repeated-measures analysis of variance showed a significant between-group difference during the study period in favor of the surgical group (P = 0.039). For arm pain intensity, no significant between-group differences were found according to the repeated-measures analysis of variance (P = 0.580). Eighty-seven percent of the patients in the surgical group rated their symptoms as “better/much better” at the 12-month follow-up compared with 62% in the nonsurgical group (P < 0.05). At 24 months, the corresponding figures were 81% and 69% (P = 0.28). The difference was significant only at the 12-month follow-up in favor of the surgical group. Significant reduction in Neck Disability Index, neck pain, and arm pain compared with baseline was seen in both groups (P < 0.001). Conclusion. In this prospective, randomized study of patients with cervical radiculopathy, it was shown that surgery with physiotherapy resulted in a more rapid improvement during the first postoperative year, with significantly greater improvement in neck pain and the patient's global assessment than physiotherapy alone, but the differences between the groups decreased after 2 years. Structured physiotherapy should be tried before surgery is chosen. Level of Evidence: 2

We present the case of a 50-year-old female patient with Friedreich ataxia (FA) who was treated successfully with an intrathecal baclofen (ITB)-delivering pump for painful spasms. To our knowledge, this is the second reported case of FA where ITB relieved painful and disabling spasms. We suggest that ITB should be considered in the treatment of disabling spasms in patients with FA.

This chapter reflects the yearning for discoveries within the field of spinal cord injury (SCI) and points out the difficulties, opportunities, as well as possibilities to relate and translate the results from basic science to clinical management. After a brief presentation of "spinal cord history," we provide a short overview of the cornerstones of modern management of patients with SCI. This overview will, besides introducing basic scientists in the field of clinical practice, also expose the inherent imprecision of everyday clinical care compared to the high methodological requirements of experimental SCI research. We will focus our presentation on medical management aimed at preventing the consequences of secondary injury in the acute period, i.e., neuroprotection. A brief overview of various techniques of neural regeneration in the subacute (late) and chronic phase will follow this. Finally, based on the progress in basic science within the fields of neuroprotection and regeneration, some thoughts about future clinical therapeutic avenues will be discussed.

Behandlingen av akut ryggmargsskadade patienter har tre huvudmal: minimera det neurologiska bortfallet, paborja mobiliseringen sa snart som mojligt och genomfora adekvat rehabilitering. Varje nys ...

The history of spinal cord injuries starts with the ancient Egyptian medical papyrus known as the Edwin Smith Surgical Papyrus. The papyrus, written about 2500 B. C. by the physician and architect of the Sakkara pyramids Imhotep, describes "crushed vertebra in his neck" as well as symptoms of neurological deterioration. An ailment not to be treated was the massage to the patients at that time. This fatalistic attitude remained until the end of World War II when the first rehabilitation centre focused on the rehabilitation of spinal cord injured patients was opened. Our knowledge of the pathophysiological processes, both the primary as well as the secondary, has increased tremendously. However, all this knowledge has only led to improved medical care but not to any therapeutic method to restore, even partially, the neurological function.Neuroprotection is defined as measures to counteract secondary injury mechanisms and/or limit the extent of damage caused by self-destructive cellular and tissue processes. The co-existence of several distinctly different injury mechanisms after trauma has provided opportunities to explore a large number of potentially neuroprotective agents in animal experiments such as methylprednisolone sodium succinate. The results of this research have been very discouraging and pharmacological neuroprotection for patients with spinal cord injury has fallen short of the expectations created by the extensive research and promising observations in animal experiments. The focus of research has now, instead, been transformed to the field of neural regeneration. This field includes the discovery of regenerating obstacles in the nerve cell and/or environmental factors but also various regeneration strategies such as bridging the gap at the site of injury as well as transplantation of foetal tissue and stem cells. The purpose of this review is to highlight selected experimental and clinical studies that form the basis for undertaking future challenges in the research field of spinal cord injury. We will focus our discussion on methods either preventing the consequences of secondary injury in the acute period ( neuroprotection) and/or various techniques of neural regeneration in the sub-acute and chronic phase and finally expose some thoughts about future avenues within this scientific field.

Systemic hypothermia has been shown to exert neuroprotective effects in experimental ischemic CNS models caused by vascular occlusions. The present study addresses the question as to whether systemic hypothermia has similar neuroprotective qualities following severe spinal cord compression trauma using microtubule-associated protein 2 (MAP2) immunohistochemistry combined with the avidin-biotin-peroxidase complex method as marker to identify neuronal and dendritic lesions. Fifteen rats were randomized into three equally sized groups. One group sustained thoracic laminectomy, the others severe spinal cord compression trauma of the T8-9 segment. The control group contained laminectomized animals submitted to a hypothermic procedure in which the esophageal temperature was reduced from 38 °C to 30 °C. The two trauma groups were either submitted to the same hypothermic procedure or kept normothermic during the corresponding time. All animals were sacrificed 24 h following the surgical procedure. The MAP2 immunostaining in the normothermic trauma group indicated marked reductions in MAP2 antigen in the cranial and caudal peri-injury zones (T7 and T10, respectively). This reduction was much less pronounced in the hypothermic trauma group. In fact, the MAP2 antigen was present in almost equally sized areas in both the hypothermic groups independent of previous laminectomy alone or the addition of trauma. Our study thus indicates that hypothermia has a neuroprotective effect on dendrites of rat spinal cords subjected to compression trauma.

We compared two staining methods for the demonstration of dendrites under normal and pathological conditions of the rat central nervous system. MAP2- and neurogranin immunohistochemistry was applied to samples from normal tissue, spinal cord subjected to graded compression trauma, cerebral cortex following contusion trauma, and brains with focal ischemic lesions induced by occlusion of the middle cerebral artery (MCAO). Normal rats showed MAP2 immunoreactivity in nerve cell bodies and dendrites of brain and spinal cord. However, neurogranin staining was present only in nerve cell bodies and dendrites of the normal brain, and not in the spinal cord. Reduction of MAP2 immunoreactivity was seen in lesions of spinal cords subjected to compression trauma. Neurogranin staining was of no value in this experimental condition since it was not present under normal conditions. The brain contusions showed loss of both MAP2- and neurogranin immunoreactivity at the site of the lesion. MCAO resulted in an extensive loss of MAP2- and neurogranin staining in the ipsilateral hemisphere. In conclusion, our study shows that MAP2 immunostaining is a sensitive method for identifying dendritic lesions of various CNS injuries in the rat. Neurogranin immunostaining is an alternative method for investigations of dendritic pathology in the brain but not in the spinal cord.

We compared two staining methods for the demonstration of dendrites under normal and pathological conditions of the rat central nervous system. MAP2- and neurogranin immunohistochemistry was applied to samples from normal tissue, spinal cord subjected to graded compression trauma, cerebral cortex following contusion trauma, and brains with focal ischemic lesions induced by occlusion of the middle cerebral artery (MCAO). Normal rats showed MAP2 immunoreactivity in nerve cell bodies and dendrites of brain and spinal cord. However, neurogranin staining was present only in nerve cell bodies and dendrites of the normal brain, and not in the spinal cord. Reduction of MAP2 immunoreactivity was seen in lesions of spinal cords subjected to compression trauma. Neurogranin staining was of no value in this experimental condition since it was not present under normal conditions. The brain contusions showed loss of both MAP2- and neurogranin immunoreactivity at the site of the lesion. MCAO resulted in an extensive loss of MAP2- and neurogranin staining in the ipsilateral hemisphere. In conclusion, our study shows that MAP2 immunostaining is a sensitive method for identifying dendritic lesions of various CNS injuries in the rat. Neurogranin immunostaining is an alternative method for investigations of dendritic pathology in the brain but not in the spinal cord.