Safety and Efficacy of Autologous Stem Cell Treatment for Facetogenic Chronic Back Pain.

BACKGROUND: Chronic back pain due to facet joint syndrome is a common and debilitating condition. Advances in regenerative medicine have shown that autologous unmodified adipose tissue-derived regenerative cells (ADRC) provide several beneficial effects. These regenerative cells can differentiate into various tissues and exhibit a strong anti-inflammatory potential. ADRCs can be obtained from a small amount of fatty tissue derived from the patient's abdominal fat. METHODS: We report long-term results of 37 patients (age 31-78 years, mean 62.5) suffering from "Facet Joint Syndrome" The pathology was confirmed by clinical, radiological examinations and fluoroscopically guided test injections. Then, liposuction was performed. An amount of 50-100 cc of fat was harvested. To recover stem cells from adipose tissue, we use the CE-certified Transpose RT™ system from InGeneron GmbH. The cells were then injected under fluoroscopic control in the periarticular fat. Follow-up examinations were performed at 1 week, 1 year, and 5 years. RESULTS: Every patient reported improved VAS pain at any follow-up (1 week, 1 year, and 5 years) with ADRCs compared to the baseline. CONCLUSIONS: Our observational data indicate that facet joint syndrome patients treated with unmodified adipose tissue-derived regenerative cells experience improved the quality of life in the long term.

Partial Spinous Process Decompression in Baastrup's Disease: A Case Report and Literature Review.

Baastrup's disease represents a frequent, primarily radiological phenomenon on imaging studies of the spine. Nevertheless, it can present as a rare, symptomatically relevant pathology that implies a therapeutic consequence. Yet, there is little evidence and agreement on a consistent treatment strategy in the current literature. Here, we present the case of a 46-year-old man who presented with chronic, persistent midline back pain that was relieved by flexion and aggravated by spinal extension. Extensive imaging studies, including computed tomography, magnetic resonance imaging, and single-photon emission computed tomography confirmed the close approximation of the spinous processes at the levels L4-L5 and L5-S1. Clinically symptomatic isolated Baastrup's disease was confirmed by a local anesthetic infiltration test. As conservative treatment options failed, partial resection of the spinous processes was performed. Conservative treatment, including analgesics and physical therapy, represents the initial treatment approach for Baastrup's disease. When clinical features of Baastrup's disease are present, differential diagnoses have been excluded, and conventional therapy has been exhausted surgical decompression with low surgical risk and good prognosis may be indicated after careful consideration of the indications.

First immunohistochemical evidence of human tendon repair following stem cell injection: A case report and review of literature.

BACKGROUND: Current clinical treatment options for symptomatic, partial-thickness rotator cuff tear (sPTRCT) offer only limited potential for true tissue healing and improvement of clinical results. In animal models, injections of adult stem cells isolated from adipose tissue into tendon injuries evidenced histological regeneration of tendon tissue. However, it is unclear whether such beneficial effects could also be observed in a human tendon treated with fresh, uncultured, autologous, adipose derived regenerative cells (UA-ADRCs). A specific challenge in this regard is that UA-ADRCs cannot be labeled and, thus, not unequivocally identified in the host tissue. Therefore, histological regeneration of injured human tendons after injection of UA-ADRCs must be assessed using comprehensive, immunohistochemical and microscopic analysis of biopsies taken from the treated tendon a few weeks after injection of UA-ADRCs. CASE SUMMARY: A 66-year-old patient suffered from sPTRCT affecting the right supraspinatus and infraspinatus tendon, caused by a bicycle accident. On day 18 post injury [day 16 post magnetic resonance imaging (MRI) examination] approximately 100 g of abdominal adipose tissue was harvested by liposuction, from which approximately 75 × 106 UA-ADRCs were isolated within 2 h. Then, UA-ADRCs were injected (controlled by biplanar X-ray imaging) adjacent to the injured supraspinatus tendon immediately after isolation. Despite fast clinical recovery, a follow-up MRI examination 2.5 mo post treatment indicated the need for open revision of the injured infraspinatus tendon, which had not been treated with UA-ADRCs. During this operation, a biopsy was taken from the supraspinatus tendon at the position of the injury. A comprehensive, immunohistochemical and microscopic analysis of the biopsy (comprising 13 antibodies) was indicative of newly formed tendon tissue. CONCLUSION: Injection of UA-ADRCs can result in regeneration of injured human tendons by formation of new tendon tissue.

Towards a Comprehensive Understanding of UA-ADRCs (Uncultured, Autologous, Fresh, Unmodified, Adipose Derived Regenerative Cells, Isolated at Point of Care) in Regenerative Medicine.

It has become practically impossible to survey the literature on cells derived from adipose tissue for regenerative medicine. The aim of this paper is to provide a comprehensive and translational understanding of the potential of UA-ADRCs (uncultured, unmodified, fresh, autologous adipose derived regenerative cells isolated at the point of care) and its application in regenerative medicine. We provide profound basic and clinical evidence demonstrating that tissue regeneration with UA-ADRCs is safe and effective. ADRCs are neither 'fat stem cells' nor could they exclusively be isolated from adipose tissue. ADRCs contain the same adult stem cells ubiquitously present in the walls of blood vessels that are able to differentiate into cells of all three germ layers. Of note, the specific isolation procedure used has a significant impact on the number and viability of cells and hence on safety and efficacy of UA-ADRCs. Furthermore, there is no need to specifically isolate and separate stem cells from the initial mixture of progenitor and stem cells found in ADRCs. Most importantly, UA-ADRCs have the physiological capacity to adequately regenerate tissue without need for more than minimally manipulating, stimulating and/or (genetically) reprogramming the cells for a broad range of clinical applications. Tissue regeneration with UA-ADRCs fulfills the criteria of homologous use as defined by the regulatory authorities.

Effect of lumbar spinal stenosis and surgical decompression on erectile function.

STUDY DESIGN: Retrospective clinical case series. OBJECTIVE: To evaluate whether and how often patients with lumbar spinal stenosis presenting for surgery have an erectile dysfunction before and after decompressive surgery. SUMMARY OF BACKGROUND DATA: So far, there are no reported data on pre- and postoperative erectile function status for patients with lumbar spinal stenosis. METHODS: A total of 197 male patients with lumbar spinal stenosis who underwent spinal decompression between May 2006 and June 2007 were screened. Patients over 75 years, patients who had previous radical prostatectomy, and patients with psychiatric or other severe concomitant diseases were excluded. Patients with further symptoms for cauda equina syndrome were excluded as well. The erectile function of the remaining 38 patients with a mean age of 63 years was retrospectively rated before and after lumbar spinal decompression using a standardized questionnaire (International Index of Erectile Function-5). Additionally, pre- and postoperative pain, quality of life, and walking distance were assessed. RESULTS: As expected severe preoperative back and leg pain significantly decreased after decompressive surgery. This was associated with a significant increase in the quality of life. The incidence of erectile dysfunction before and after surgery was higher compared to population-based standard data, and surgery was associated with a significant decrease of erectile function at latest follow-up (9.7 months). CONCLUSION: Lumbar spinal stenosis is associated with a neglected prevalence of erectile dysfunction. Surprisingly, it does not improve after decompressive spinal surgery; moreover, a decline was observable. Underlying mechanisms of the postoperative decline remain obscure.

Effects of temporary clipping during aneurysm surgery.

OBJECTIVE: Intraoperative aneurysm rupture is associated with a high morbidity and mortality. Temporary vessel occlusion is an integral part of aneurysm clipping to avoid intraoperative hemorrhage. The information concerning the role of temporary occlusion regarding the development of cerebral vasospasm is sparse. The aim of this study was to provide more information in this field. METHODS: We operated on 292 patients suffering from cerebral aneurysms. The data were reviewed from a prospectively collected databank, which includes information about the severity of subarachnoid hemorrhage, as well as transcranial Doppler data and surgical data such as temporary occlusion. RESULTS: In 50% of our patients, temporary occlusion was performed during surgery. Twenty-nine percent showed an ischemic lesion in the CCT post-operatively, and in 58% of these patients, temporary occlusion was performed (versus 47% without temporary occlusion, p = 0.09). The mean occlusion time was longer in patients with radiologic signs of infarction. Furthermore, patients having unfavorable outcome showed a longer temporary occlusion time. Thirty-four percent of patients who underwent temporary vessel occlusion developed vasospasm postoperatively (versus 20% without temporary occlusion, p < 0.006). Temporary occlusion time correlated to the development of vasospasm as defined by transcranial Doppler flow velocity. Forty-eight percent of the patients treated using temporary occlusion suffered from middle cerebral artery aneurysm (versus 22% without temporary occlusion, p < 0.0001). An increased blood flow velocity was mostly seen in this region (p < 0.003). CONCLUSION: According to our results, it seems to be the possible that temporary vessel occlusion is an additional factor in aggravating vasospasm after aneurysmatic subarachnoid hemorrhage.

Quality of Life following Surgery for Malignancies of the Anterior Skull Base.

Radical surgery combined with postoperative radiation is recommended to achieve the best outcomes in patients suffering from malignant anterior skull base tumors. However, information on the impact of such treatment on the quality of life of these patients is sparse. This retrospective study evaluated quality of life in patients with anterior skull base malignancies after transdural resection and radiotherapy. At follow-up, 36% of the patients were alive (mean survival time, 39 months). Only 45% of the patients were able to work in their previous occupation a mean of 15 months after surgery. At follow-up, 58% of the patients had a recurrent tumor. The mean quality of life index was 42 points (range, 0 to 100). The lowest values were on the job item, and the highest mean value was on the family item. All patients, dependents, or both would agree to surgery in the future. Based on these findings, quality of life after transdural surgery for the treatment of anterior skull base malignancies seems to be low.

Doppler ultrasound measurement of blood flow volume in the extracranial internal carotid artery for evaluation of brain perfusion after aneurysmal subarachnoid hemorrhage.

Monitoring of cerebral blood flow (CBF) is an essential part in the early diagnosis of cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH). Several methods have been established to monitor cerebral perfusion in these patients. During last few years, a new sonographic approach has been introduced, the so called 'angle independent ultrasound system' for monitoring volume flow in the internal carotid artery (ICA). The angle independent Doppler ultrasound system Quantix ND (Cardiosonix Ltd, Israel) determines the diameter of the ICA as well as the velocity of blood flow in the extracranial part of this vessel. Thus, a determination of the global CBF in the anterior circulation can be achieved. Aim of our study was to compare the Quantix ND system and the commonly used transcranial Doppler sonography (TCD) in patients suffering from aneurysmal SAH. We included 11 patients (eight female and three male; Hunt and Hess I-V) and performed post-operatively/post-interventionally daily measurement of blood flow volume in the ICA, and determined the blood flow velocity in middle and anterior cerebral artery (MCA and ACA) with TCD. Six patients post-operatively/post-interventionally developed cerebral vasospasm, resulting in ischemia and territorial infarction. Three patients were chosen as case studies. In contrast to the TCD, we found a strong significant correlation of blood flow volume with Quantix ND in the ICA and the occurrence of cerebral infarction (p<0.001). These preliminary data justify further investigation of this angle independent Doppler ultrasound device. We postulate that this new tool might be effective for monitoring the CBF in the critical post-operative/post-interventional interval following aneurysmal SAH.

Molecular mechanisms of cerebral vasospasm following aneurysmal SAH.

Cerebral vasospasm following aneurysmal vasospasm has been the subject of intensive research. However the underlying pathophysiological mechanisms remain obscure. This article should summarize the present state concerning smooth muscle contraction, endothelial dysfunction, inflammatory changes, gene expression, in the genesis of vasospasm following aneurysmal subarachnoid hemorrhage.

Comparison of craniotomy and craniectomy in patients with acute subdural haematoma.

Despite the increasing acceptance of craniectomy in patients with traumatic brain injury, the value of early decompressive craniectomy in patients with acute subdural haematoma is still under debate. In this retrospective study, we reviewed 180 patients with traumatic acute subdural haematoma, 111 of whom were treated with haematoma evacuation via craniotomy and 69 of whom were treated with early decompressive craniectomy. Due to the higher incidence of signs of herniation for patients in the craniectomy group, the mortality rate in this group was higher than that in the craniotomy group (53% vs. 32.3%). However, overall there was no significant difference in outcome between the two groups. Age and clinical signs of herniation were significantly associated with an unfavourable outcome, regardless of the type of surgery. Decompressive craniectomy did not seem to have a therapeutic advantage over craniotomy in traumatic acute subdural haematoma.

The history and present status of deep hypothermia and circulatory arrest in cerebrovascular surgery.

After the development of deep hypothermia and circulatory arrest for cardiothoracic procedures in the late 1950s, this technique was adopted by several neurosurgeons as an aid to complex cranial surgery. Woodhall and colleagues described its first use for a neurosurgical procedure in 1960. Although their case did not involve a cerebrovascular procedure, the technique was subsequently used for the surgical treatment of cerebrovascular lesions, especially complex and giant aneurysms as well as large and solid hemangioblastomas. At the beginning, incorporation of this technique into common neurosurgical practice was impeded by several factors. For example, postbypass coagulopathy had been a serious source of morbidity. Furthermore, the need for cooperation among multiple subspecialties and the requirements for expensive equipment had further limited the availability of this technique. Subsequent improvements in the technique and advances in the equipment designed for cardiopulmonary bypass have led to its more widespread use starting in the 1980s. Hypothermic circulatory arrest has been described in several reports as a safe and useful tool in the treatment of large and giant aneurysms. Nevertheless, improvements in endovascular procedures and further refinement in skull base surgical techniques have limited the indications for circulatory arrest and deep hypothermia. The authors describe the history of hypothermia and circulatory arrest, its implementation in cerebrovascular surgery, and the changes in indications for and results of its use over time.

Pyogenic spinal infections and outcome according to the 36-item short form health survey.

OBJECT: Pyogenic vertebral infections are rare. In most papers investigators have focused on risk factors, clinical characteristics, and diagnostic findings, and discussed different management strategies. The optimal strategy for dealing with spinal infections, however, remains controversial. Additionally, outcome data regarding quality of life (QOL) after pyogenic spinal infections are sparse. The aim of this study was to provide further data in this field. METHODS: The authors retrospectively investigated 62 patients suffering from pyogenic spinal infections. In 37 patients (59%), lumbar lesions were observed; thoracic and thoracolumbar infections were documented in 19 (31%) and a cervical infection was demonstrated in six patients (10%). Overall 28 patients (45%) underwent conservative treatment, and 34 (55%) underwent surgery with or without the placement of instrumentation. At follow-up examination the authors recorded each patient's satisfaction as well as QOL according to the 36-Item Short Form Health Survey. Quality of life after treatment of pyogenic spine infections did not reach the level of the normative sample. Most patients continued to suffer some sort of pain. Despite different indications, the surgically treated patients experienced a slightly better QOL and self-reported satisfaction levels, as well as a statistically significant better outcome, than patients treated conservatively. CONCLUSIONS: The results obtained in the present study suggest that surgery, especially in conjunction with the placement of instrumentation, may be more beneficial than conservative treatment in patients with a spinal infection.

ICAM-1 and VCAM-1 expression following aneurysmal subarachnoid hemorrhage and their possible role in the pathophysiology of subsequent ischemic deficits.

BACKGROUND: The pathophysiology of ischemic cerebral lesions following aneurysmal subarachnoid hemorrhage (SAH) is poorly understood. There is growing evidence that inflammatory reactions could be involved in the pathogenesis of such delayed occurring ischemic lesions. The aim of this study was to evaluate adhesion molecules with regard to these lesions following SAH. METHODS: Serum and cerebrospinal fluid (CSF) samples were taken daily from 15 patients up to day 9 after SAH and evaluated for intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1). RESULTS: CSF and serum samples correlated well during nearly the whole time course (p < 0.0001). A secondary increase in ICAM-1 and VCAM-1 in the serum and CSF correlated with an increase in flow velocity in the transcranial Doppler (p > 0.0001 and p < 0.007) but not to a delayed lesion in the CT scan. CONCLUSION: We believe that inflammatory processes are involved in the pathogenesis of cerebral vasospasm but they might only be a part of a multifactorial pathogenesis.

High re-bleeding rate in young adults after subarachnoid haemorrhage from giant aneurysms.

Low re-bleeding rates within the first 14 days of aneurysmal subarachnoid haemorrhage are reported in young patients. Furthermore, re-bleeding rate for giant aneurysms does not exceed 20% according to the literature. Our own clinical impression is that the re-bleeding rate seems to be much higher in giant aneurysms than reported, particularly in young patients. The aim of this study was to evaluate re-bleeding rate after subarachnoid haemorrhage following rupture of giant aneurysms in a younger population. We reviewed records of 23 patients who were treated in our institution for subarachnoid haemorrhage from giant aneurysms between 1994 and 2003. By definition, the aneurysms were larger than 25 mm in diameter. Five patients were younger than 40 years of age at the time of the aneurysmal subarachnoid haemorrhage. All younger patients (<40 years of age) showed re-bleeding after the first subarachnoid haemorrhage within the first 14 days of the initial event. In four patients (20%) older than 40 years at the time of the haemorrhage re-bleeding could be observed within the first 14 days of subarachnoid haemorrhage. We can confirm the re-bleeding rate of approximately 20% in patients suffering from subarachnoid haemorrhage (SAH) in the group of patients older than 40 years of age. However, younger patients seem to be at much higher risk of re-bleeding from giant aneurysms.

Possible role of the C-reactive protein and white blood cell count in the pathogenesis of cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

The delayed ischemic neurologic deficit (DIND) is a common and potentially devastating complication in patients who have sustained subarachnoid hemorrhage (SAH). Recent evidence suggests that various constituents of the inflammatory response may be critical in the pathogenesis of this ischemic complication. The aim of this study was to evaluate the possible relationship between the C-reactive protein (CRP)/white blood cell (WBC) count and DIND. A total of 88 patients with acute SAH were included. CRP and WBC count were estimated on a daily basis. Outcome was evaluated 1 year after the initial ictus according to the Glasgow Outcome Scale. CRP levels on days 5, 6, 7, and 8 were statistically significantly higher in the group of patients developing a DIND (P < 0.025, P < 0.016, P < 0.011, P < 0.0002). WBC counts were higher in this patient group on days 1, 4, 5, 6, and 7 (P < 0.0253, P < 0.0087, P < 0.00167, P < 0.0026, P < 0.0045). Overall CRP values were higher with increasing severity of the initial ictus according to the Hunt and Hess Scale and to the outcome according to the Glasgow Outcome Scale from day 3 on. A statistically significant relationship between WBCs and outcome could not be observed. The presented data do not prove that WBCs and CRP values have a direct contribution to the pathogenesis of ischemic complications following SAH, but it supports the assertion that inflammation may present a common pathogenic pathway in the development of such complications.

A large, erosive intraspinal and paravertebral gout tophus. Case report.

Symptomatic gout tophi of the spine are a rare but well-characterized complication of tophaceous gout. The authors report the case of a 29-year-old previously healthy man who presented with L-5 radiculopathy. Lumbar magnetic resonance (MR) imaging revealed a 4.5 x 4.5 x 2.8-cm large gout tophus mimicking a malignant spinal tumor or abscess. The tophus completely destroyed both L-4 and L-5 facet joints and the left L-4 lamina and spread epidurally from L-3 to L-5, compressing the left L-5 nerve root. There has been no similar case reported so far with respect to the extent of bone destruction. The authors describe the case history and present intraoperative, MR imaging, and histological findings.

A mathematical model of cerebral circulation and oxygen supply.

A compartment model of cerebral circulation and oxygen supply including an autoregulation mechanism is presented. The model is focused on the analysis of slow dynamical variations of long term neurophysiological parameters like the partial oxygen pressure of brain tissue or the cerebral blood flow. The circulatory part of the model is built up of seven compartments including arteries, capillaries, veins, brain tissue, cerebrospinal fluid, the sagittal sinus and an artificial compartment for the simulation of brain swelling. The description of oxygen supply is based on a Krogh model. Numerical calculations reproduce the experimentally well established connection between arterial blood pressure and the production of cerebrospinal fluid. Furthermore we found an approximately linear correlation of the partial oxygen pressure of brain tissue to the mean arterial blood pressure in the case of an impaired autoregulation mechanism. In a first test such a linear dependence could also be detected in clinical data from the neurosurgical intensive care monitoring.

Ventricular tapping seems to have no influence on S-100B and NSE serum concentrations.

Serum markers, e.show $132#g., the protein S-100B and neuron-specific enolase (NSE), are recognized to give additional information about the extension and prognosis of brain damage. In some of these patients it is necessary to insert a ventricular drain. Whether the cannulation of the ventricle falsifies the serum concentrations of these markers is unknown. The aim of this study was to get further information in this field. In this prospective study we included 19 patients. All patients underwent ventricular tapping and insertion of a ventricular drain. Serum samples for estimation of S-100B and NSE were collected before, directly after and 6 h after insertion. In addition we investigated the cerebrospinal fluid (CSF) directly after and 6 h after insertion. All patients but one showed no significantly increased S-100B or NSE serum concentration after insertion of the drainage. The concentrations in the CSF were significantly higher. One patient showed increasing concentrations of the markers in all samples reflecting ongoing brain damage. The serum values of S-100B and NSE seem not to be falsified by insertion of a ventricular drain. Therefore the prognostic value of these serum markers seems to be preserved despite the surgical manipulation.

Hyperemia following aneurysmal subarachnoid hemorrhage: incidence, diagnosis, clinical features, and outcome.

OBJECTIVE: Hyperemia is a known phenomenon after aneurysmal subarachnoid hemorrhage, but only a few reports describe and analyze hyperemia in these patients. This could be the result of diagnostic difficulties in order to identify elevated cerebral blood flow; thus, it seems that hyperemia could be an underdiagnosed clinical state. The aim of the study was to evaluate this phenomenon in comparison with clinical outcome and imaging data in order to describe the frequency of hyperemia after subarachnoid hemorrhage and maybe improve clinical diagnosis. DESIGN: Retrospective analysis of our cerebral blood flow and transcranial Doppler sonography data bank. SETTING: . Neurosurgical/Anesthesiological intensive care unit University of Regensburg, Regensburg, Germany. PATIENTS AND PARTICIPANTS: A total of 37 patients were included (24 women and 13 men). All patients suffered from aneurysmal subarachnoid hemorrhage. MEASUREMENTS AND RESULTS: Standard transcranial Doppler ultrasonography, as well as the Xenon(133) clearance technique for cerebral blood flow measurements, was employed. We observed 37 increases of flow velocities in 37 patients according to Doppler ultrasonography. In order to distinguish between ischemia and hyperemia a Xenon(133) regional cerebral blood flow examination was performed. Global hyperemia was detected in 5 patients (14%). Hyperemia correlated only to favorable outcome ( p=0.01) and fewer ischemic lesions in the computed tomography ( p<0.05). CONCLUSION: The results indicate that while global hyperemia is a frequent phenomenon that cannot be detected by standard Doppler ultrasonography or clinical examination, hyperemic cerebral blood flow values following aneurysmatic subarachnoid hemorrhage are correlated to favorable outcome.