Bogdan Czapiga

Transplantation of autologous olfactory ensheathing cells in complete human spinal cord injury.

Numerous studies in animals have shown the unique property of olfactory ensheathing cells to stimulate regeneration of lesioned axons in the spinal cord. In a Phase I clinical trial, we assessed the safety and feasibility of transplantation of autologous mucosal olfactory ensheathing cells and olfactory nerve fibroblasts in patients with complete spinal cord injury. Six patients with chronic thoracic paraplegia (American Spinal Injury Association class A-ASIA A) were enrolled for the study. Three patients were operated, and three served as a control group. The trial protocol consisted of pre- and postoperative neurorehabilitation, olfactory mucosal biopsy, culture of olfactory ensheathing cells, and intraspinal cell grafting. Patients clinical state was evaluated by clinical, neurophysiological, and radiological tests. There were no adverse findings related to olfactory mucosa biopsy or transplantation of olfactory ensheathing cells at 1 year after surgery. There was no evidence of neurological deterioration, neuropathic pain, neuroinfection, or tumorigenesis. In one cell-grafted patient, an asymptomatic syringomyelia was observed. Neurological improvement was observed only in transplant recipients. The first two operated patients improved from ASIA A to ASIA C and ASIA B. Diffusion tensor imaging showed restitution of continuity of some white matter tracts throughout the focus of spinal cord injury in these patients. The third operated patient, although remaining ASIA A, showed improved motor and sensory function of the first spinal cords segments below the level of injury. Neurophysiological examinations showed improvement in spinal cord transmission and activity of lower extremity muscles in surgically treated patients but not in patients receiving only neurorehabilitation. Observations at 1 year indicate that the obtaining, culture, and intraspinal transplantation of autologous olfactory ensheathing cells were safe and feasible. The significance of the neurological improvement in the transplant recipients and the extent to which the cell transplants contributed to it will require larger numbers of patients.

Functional regeneration of supraspinal connections in a patient with transected spinal cord following transplantation of bulbar olfactory ensheathing cells with peripheral nerve bridging.

Treatment of patients sustaining a complete spinal cord injury remains an unsolved clinical problem because of the lack of spontaneous regeneration of injured central axons. A 38-year-old man sustained traumatic transection of the thoracic spinal cord at upper vertebral level Th9. At 21 months after injury, the patient presented symptoms of a clinically complete spinal cord injury (American Spinal Injury Association class A-ASIA A). One of the patients olfactory bulbs was removed and used to derive a culture containing olfactory ensheathing cells and olfactory nerve fibroblasts. Following resection of the glial scar, the cultured cells were transplanted into the spinal cord stumps above and below the injury and the 8-mm gap bridged by four strips of autologous sural nerve. The patient underwent an intense pre- and postoperative neurorehabilitation program. No adverse effects were seen at 19 months postoperatively, and unexpectedly, the removal of the olfactory bulb did not lead to persistent unilateral anosmia. The patient improved from ASIA A to ASIA C. There was improved trunk stability, partial recovery of the voluntary movements of the lower extremities, and an increase of the muscle mass in the left thigh, as well as partial recovery of superficial and deep sensation. There was also some indication of improved visceral sensation and improved vascular autoregulation in the left lower limb. The pattern of recovery suggests functional regeneration of both efferent and afferent long-distance fibers. Imaging confirmed that the grafts had bridged the left side of the spinal cord, where the majority of the nerve grafts were implanted, and neurophysiological examinations confirmed the restitution of the integrity of the corticospinal tracts and the voluntary character of recorded muscle contractions. To our knowledge, this is the first clinical indication of the beneficial effects of transplanted autologous bulbar cells.

The olfactory bulb and olfactory mucosa obtained from human cadaver donors as a source of olfactory ensheathing cells.

During the last decade, olfactory ensheathing cells (OECs) have been successfully applied in multiple experimental approaches aimed to repair damaged mammalian spinal cord. Some of these experiments have consequently been translated into clinical trials. Finding a reliable source of human OECs that is easily accessible and can ensure a sufficient number of cells is a major prerequisite for conducting studies on OEC‐mediated spinal cord regeneration. Here, we present a procedure for obtaining olfactory bulbs (OBs) and olfactory mucosa (OM) simultaneously from adult cadaver heart‐beating donors for OEC isolation and analyze some of the factors that may condition successful OEC culture. We show that the results of OEC culture from OBs (10 cases) correlated significantly with warm ischemia time (WIT) as well as the initial viability of the isolated cells. Efficient OEC culture was possible when the WIT for the OB was up to 20 min. Brain damage, assessed by determination of S100B serum level, was not related to the success of OEC culture from the OB. Cadaver OM (7 cases) was shown to be a more reliable source of human OECs than the OB. In most of the examined cases the efficacy of culturing OECs from cadaver OM obtained even 180 min after cardiac arrest was comparable to that of living patients. The method of obtaining OBs and OM from cadavers enables the use of an alternative source of primary adult human OECs for further preclinical and clinical studies on their neurotrophic properties.

Elevated BUBR1 Expression Is Associated with Poor Survival in Early Breast Cancer Patients: 15-Year Follow-up Analysis

BUBR1 (budding uninhibited by benzimidazole-related 1) represents the component of a controlling complex in mitosis. Defects in mitotic control complex result in chromosomal instability and, as a result, disturb the mitotic process. This study was aimed at examining the prognostic value linked to the expression of BUBR1 in a group of patients with breast cancer. We analyzed the expression of BUBR1 in 98 stage II breast cancer patients with a median follow-up of 15 years. Immunohistochemical reactions were performed using monoclonal antibodies against BUBR1. We also studied the prognostic value of BUBR1 mRNA expression using the Kaplan-Meier (KM) plotter, which assessed the effect of 22,277 genes on survival in 2422 breast cancer patients. A background database was established using gene expression data and survival information on 2422 patients downloaded from the Gene Expression Omnibus (GEO; Affymetrix HGU133A and HGU133+2 microarrays). The median relapse-free survival was 6.43 years. Univariate and multivariate analyses showed that higher expression of BUBR1 was typical for cases of shorter overall survival, disease-free time, and disease-specific survival. KM plotter analysis showed that elevated BUBR1 mRNA expression had a negative impact on patients’ relapse-free, distant metastases–free, and overall survival. Elevated BUBR1 expression was associated with poor survival in early stage breast cancer patients.

Usefulness of perfusion weighted magnetic resonance imaging with signal-intensity curves analysis in the differential diagnosis of sellar and parasellar tumors: Preliminary report

PURPOSE The most common pituitary tumors are adenomas, which however may be mimicked by other tumors that can show a very similar appearance in plain MRI. The aim of our study was to evaluate the usefulness of perfusion weighted MR imaging (PWI), including signal-intensity curves analysis in the differential diagnosis of sellar/parasellar tumors. METHODS Forty-one patients with sellar/parasellar tumors (23 macroadenomas, 10 meningiomas, 5 craniopharyngiomas, 1 intrasellar hemangioblastoma, 1 intrasellar prostate cancer metastasis, 1 suprasellar glioma), underwent plain MRI followed by PWI using a 1.5T unit. In each tumor, the mean and maximum values of relative cerebral blood volume (rCBV), as well as the relative peak height (rPH) and the relative percentage of signal intensity recovery (rPSR) were calculated. RESULTS The high perfusion tumors were: macroadenomas, meningiomas, squamous-papillary type of craniopharyngiomas, hemangioblastoma, glioma and metastasis. The low perfusion neoplasms included adamantinomatous type of craniopharyngiomas. By comparing adenomas and meningiomas, we found statistically significant differences in the mean and maximum rCBV values (p=0.026 and p=0.019, respectively), but not in rPH and rPSR. The maximum rCBV values >7.14 and the mean rCBV values >5.74 with the typical perfusion curve were very suggestive of the diagnosis of meningioma. There were differences between adenomas and other high perfusion tumors in rPH and rPSR values. CONCLUSIONS PWI can provide additional information helpful in differential diagnosis of sellar/parasellar tumors. In our opinion PWI, as an easy to perform and fast technique should be incorporated into the MR protocol of all intracranial neoplasms including sellar/parasellar tumors.

Izolowane zapalenie stawu międzykręgowego jako rzadka przyczyna ostrego i przewlekłego zespołu bólowego odcinka lędźwiowo-krzyżowego kręgosłupa – opis przypadku i przegląd literatury.

Summary Background: The most common cause of low back pain is degenerative disease of the intervertebral disc and other structures of the lumbar spine. However, in some cases other less frequent causes of such pain can be seen, for example septic facet joint arthritis. Until now, only 40 cases of such inflammatory changes within the spine have been reported in the literature. The disease is probably underestimated due to improper diagnostic pathway. Case Report: The authors describe a case of a 53-year-old woman who was repeatedly hospitalized during a five-month period because of an acute, severe low back pain, with sphincter dysfunction, partially resembling sciatic symptoms. Physical examinations revealed also focal tenderness in the area of the lumbar spine. Inflammatory markers (ESR – erythrocyte sedimentation rate, CRP – C-reactive protein) were elevated. Conservative analgetic treatment brought only partial and temporary relief of the pain and symptoms. The final accurate diagnosis of isolated septic facet joint arthritis at the level of L5/S1 was established after several months from the onset of the first symptoms, after performing various imaging examinations, including bone scintigraphy as well as CT and MRI of the lumbosacral spine. The patient fully recovered after antibiotic therapy and surgery, which was proven in several follow-up examinations showing no relevant pathology of the lumbar spine. The authors broadly describe the etiology and clinical symptoms of the septic facet joint arthritis as well as the significant role of imaging methods, especially MRI, in diagnostic process. The authors also discuss currently available treatment options, both conservative and surgical. Conclusions: The diagnostic procedure of septic facet joint arthritis requires several steps to be taken. Establishing a correct diagnosis may be difficult, that is why it is important to remember about rare causes of low back pain and to perform detailed physical examination, laboratory tests and choose appropriate imaging techniques.

Aneurismal subarachnoid hemorrhage: who remains for surgical treatment in the post-ISAT era?

Introduction Although there have been a number of studies on changes and trends in the management of aneurismal subarachnoid hemorrhage (aSAH) since publication of the International Subarachnoid Aneurysm Trial (ISAT), no data exist on what category of patients still remains for surgical treatment. Our goal was to investigate the changes that occurred in the characteristics of a population of aSAH patients treated surgically in the post-ISAT period in a single neurosurgical center, with limited availability of endovascular service. Material and methods The study included 402 aSAH patients treated surgically in our unit between January 2004 and December 2011. Each year, data regarding number of admissions, age, aneurysm location and size, clinical and radiological presentation, outcome and mortality rates were collected and analyzed. Results The annual number of admissions more than halved in the study period (from 69 in 2004 to 32 in 2011). There were no linear trends regarding patients’ mean age, clinical presentation and outcomes, but the number of patients in Fisher grade 4 increased and mortality slightly decreased. An unexpected, statistically significant increase occurred in the incidence of anterior communicating artery aneurysms (from 36.2% to 50%) and medium size aneurysms (from 34.7% to 56.2%) treated surgically, with a corresponding decrease in the incidence of middle cerebral artery aneurysms (from 40.5% to 34.3%) and large aneurysms (from 21.7% to 12.5%). Conclusions Unexpected trends in characteristics of aSAH patients treated surgically could be related to treatment decision modality. Trend patterns could be properly expressed in the constant availability of endovascular services.

Recovery and quality of life in patients with ruptured cerebral aneurysms.

Purpose: Subarachnoid hemorrhage (SAH) secondary to ruptured cerebral aneurysm is a common and frequently devastating condition with a high mortality and morbidity among survivors. The purpose of this study was to conduct a long‐term follow‐up of SAH patients, assess the changes in functional outcomes, describe quality of life (QOL), and determine its predictors 3.6 years after the hemorrhage. Design: The study design is an exploratory, descriptive correlational design. Methods: Results were collected from a sample of 113 SAH survivors treated in our institution over a 2‐year period (January 2006 until December 2007). We collected data on early and long‐term functional outcomes and compared the differences. The health‐related QOL was measured using the Polish version of The Short Form – 36 Health Survey Questionnaire (SF‐36v2). Multivariable logistic regression was derived to define independent predictors of the QOL. Findings: The mean follow‐up time was 3.6 years. Sixty‐six percent of patients had improvement in functional outcomes and among previously employed people 56% returned to work. QOL deteriorated in 24% of patients with the most affected dimension of Physical Role. Factors that predict good QOL are male gender, younger age, good economic/professional status, lack of physical handicaps, rehabilitation in a professional center, subjective improvement in health status, and absence of headaches or physical decline. Conclusions and Clinical Relevance: Recovery process in SAH patients is dynamic and progresses over time. Since physical handicaps and low economic status significantly reduce the quality of life, an effort should be made to provide intensive rehabilitation and to encourage SAH survivors to return to work.

Unusual presentation of recurrent pituitary abscess. A case report and literature review.

Pituitary abscess is a rare pituitary pathology which may be potentially life-threatening if not treated. Therefore, early accurate diagnosis and therapy are extremely important. However, the clinical diagnosis is difficult because there are no clinical symptoms characteristic of pituitary abscess. It is frequently indistinguishable clinically or with neuroimaging studies from other pituitary lesions. The MR diagnosis of pituitary abscess must be suspected in cases of sellar cystic mass with a peripheral rim enhancement after contrast administration. It must be highlighted that pituitary abscess may show various signal intensity on T1-weighted images, as in our case, making the diagnosis even more difficult. We report an unusual case of a 66-year-old woman who presented with a recurrent pituitary abscess, initially misdiagnosed as a pituitary adenoma because of its high signal intensity on T1-weighted images. The woman was operated on three times, using transsphenoidal access with a good final outcome.

Unruptured Intracranial Aneurysms: Surgery Still Safe as a Treatment Option

BACKGROUND Despite a number of studies on the treatment of unruptured intracranial aneurysms (UIA), the optimal method still remains unclear. OBJECTIVES The aim of the study was to demonstrate that UIA clipping is a safe procedure and can be a good alternative for patients not qualified for endovascular procedures and who have refused conservative management. MATERIAL AND METHODS Results were gathered from a sample of 104 patients with UIA treated in our facility over a 9-year period starting January 2005. The data from a medical database was collected, followed by a long-term assessment of the functional outcomes using the modified Rankin Scale (mRS) and of quality of life (QoL) using a SF-36 questionnaire and comparing it to a Polish population reference. RESULTS Overall postoperative morbidity was 5.7% and the mortality rate was 0%. The mean follow-up period was 6.5 years. A favorable outcome (mRS 0-2) was achieved in all the patients. Ninety-eight patients achieved an mRS score of 0, 2 patients an mRS score of 1, and 4 patients an mRS score of 2. All patients lived at home. Sixty-nine point two percent were fully employed, 27.0% were retired because of age, and only 3.8% relied on government help due to postoperative disability. The QoL index was similar to that of the standard Polish population. CONCLUSIONS In unruptured cerebral aneurysms, clipping is a safe procedure that provides good outcomes and an unaffected quality of life. It remains a good option especially for patients with MCA aneurysms that are not appropriate for endovascular management.