Marcin Czyz

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.

Prospective study on the efficacy of low-field intraoperative magnetic resonance imaging in neurosurgical operations.

BACKGROUND AND PURPOSE The application of intraoperative magnetic resonance imaging (iMRI) is related to a series of challenges of both a technical and an organizational nature. We present our experience in the application of low-field iMRI in everyday neurosurgical practice. MATERIAL AND METHODS A group of 58 patients operated on using low-field iMRI was subject to prospective controlled observation. The significance of differences in the range of preparation time, duration and direct operation results between the iMRI group and controls was analysed. The influence of epidemiological and demographic factors and technical aspects related to iMRI application on direct outcome of the surgery was assessed. RESULTS Twenty-eight tumour resections using craniotomy, 17 transsphenoidal resections of pituitary adenomas and 13 stereotactic procedures were conducted in the group of 24 men and 34 women operated on using iMRI. The control group was not significantly different in terms of epidemiological and demographic factors. The preparation and operation times were significantly longer in the iMRI group (p < 0.001 and p = 0.002, respectively). Longer duration of the surgery was not related to an increased frequency of complications. A higher percentage of postoperative improvement in neurological status (31% vs. 14%, p = 0.045), lower complication percentage (10% vs. 28%, p = 0.03) and a similar time of hospitalization (13 ± 7 vs. 12 ± 4 days, p = 0.33) were noted in the iMRI group. CONCLUSIONS The application of low-field iMRI prolongs the duration of neurosurgical procedures but does not negatively influence their safety. It is associated with above-average functional results and a lower percentage of total complications.

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.

Intraspinal Pressure Monitoring and Extensive Duroplasty in the Acute Phase of Traumatic Spinal Cord Injury: A Systematic Review

OBJECTIVE The prognosis in cervical spinal cord injury is poor, and surgical and neurointensive care management need further improvement. Monitoring of the intraspinal pressure (ISP) at an early stage after traumatic spinal cord injury (tSCI) is useful clinically. MATERIALS AND METHODS Obtaining continuous spinal cord perfusion pressure (SCPP) measurements based on the difference between mean arterial pressure and ISP allows offering best medical and surgical treatment during this critical phase of tSCI. A search was carried out with PubMed, Embase, and Google Scholar up to January 10, 2017. Articles resulting from these searches and relevant references cited in those articles were reviewed. RESULTS The optimal SCPP was found to be between 90 and 100 mm Hg and mean arterial pressure of 110-130. Laminectomy alone was found to be ineffective in the reduction of ISP because it does not lower the pressure exerted by dura on the swollen spinal cord. Therefore, bony decompression with durotomy or duroplasty seems to be the procedure of choice to reduce the ISP less than 20 mm Hg. CONCLUSIONS A randomized controlled trial is required to determine whether laminectomy with durotomy and monitoring of ISP with SCPP optimization improve neurological recovery after tSCI.

Obtaining the olfactory bulb as a source of olfactory ensheathing cells with the use of minimally invasive neuroendoscopy-assisted supraorbital keyhole approach-cadaveric feasibility study

Abstract Background. Obtaining the human olfactory bulb (OB) for treatment of spinal cord injuries with olfactory ensheathing cells (OECs) requires the elaboration of a surgical approach that could meet the criteria of safety and minimal invasiveness. The aim of the study was to evaluate the suitability of the keyhole supraorbital craniotomy (SOC) with an eyebrow incision for obtaining OB for therapeutic purposes. Methods. Seventeen SOCs were performed on nine fresh adult cadavers. The procedure of obtaining OB was conducted by neuroendoscope-assisted microsurgical dissection. Technical features related to the procedure were measured and adverse events were noted. The virtual three-dimensional planning was applied in six cases to verify the authorial A–C scale published previously. Results. The intact OB was obtained in 10 (59%) cases and a minor injury was discovered in another 5 (29%) cases. In 2 (12%) specimens OB was severely damaged which was correlated with the minor neural tissue injury (Fi2 = 0.44). While no case of an evident vascular injury was noted, there were 3 (18%) incidents of unintended frontal sinus opening positively correlated with the craniotomy width (Fi2 = 0.44). The unfavorable three-dimensional (3D) configuration of the olfactory groove area was revealed in 66% of cases and highly correlated with OB injury (Fi2 = 1.0) but not damage. Conclusions. The SOC via an eyebrow incision may be safely and effectively applied to obtain the OB as a source of OECs in roughly 90% of cases. Virtual 3D planning is useful in preoperative qualification of potential donors.

The supraorbital keyhole approach via an eyebrow incision applied to obtain the olfactory bulb as a source of olfactory ensheathing cells – radiological feasibility study

Abstract Background. The purpose of the study was to test the suitability of supraorbital keyhole craniotomy with an eyebrow incision for obtaining olfactory bulb for therapeutic purposes. Methods. Fifty three high-resolution axial head computed tomography images of patients with a mean age of 55 ± 15 years were used. The exclusion criterion was a pathology of the anterior skull base. The virtual keyhole supraorbital craniotomy was placed on each side of a three-dimensional skull model with respect to the anatomical landmarks. Trajectories of neurosurgical instrument transitions to the anterior and posterior aspects of olfactory grooves (OGs) were subsequently designed with the use of a neuronavigation planning station and measured with correction allowing the avoidance of collisions with skull base structures. Three types of anatomical configuration were divided, reflecting the extent of the correction needed to reach the bottom of OG. Results. Simulation of the surgical access and consequent metrological analysis was performed on 97 skull sides – 9 (8.5%) sides were excluded due to the large frontal sinus. The mean length of the craniotomy basis was 30.71 mm, lengths of the anterior and posterior trajectories were 53.25 and 58.24 mm, respectively (p < 0.0001). In 37% of cases the value of the corrections exceeded the depth of OG. Conclusions. The supraorbital keyhole approach via an eyebrow incision may be applied to obtain the olfactory bulb as a source of olfactory ensheathing cells in over 60% of cases. Further verification and evaluation of the surgical handiness based on cadaver specimens is justifiable.

Biomechanical characteristics of the porcine denticulate ligament in different vertebral levels of the cervical spine—Preliminary results of an experimental study

BACKGROUND Few studies exist on the mechanical properties of denticulate ligaments and none report the variation in these properties at different levels of the spine. The aim of this study was to perform an experimental determination of load-extension and stress-strain characteristics of the denticulate ligament and to establish if their properties change at different vertebral levels of the cervical spine. METHOD The study was carried out on a total of 98 porcine denticulate ligament samples dissected from seven fresh porcine cervical spinal cord specimens. All of the samples were subjected to an uniaxial tensile test at a speed of 2mm/min, during which the load-extension characteristics were registered. RESULTS The analysis revealed a decrease of the failure force in the caudal orientation indicated by significant differences between the C1 (1.04±0.41N) and C7 (0.55±0.12N) vertebral levels (P=0.037). The average ultimate force that broke the denticulate ligaments was 0.88N. The mean value of Young׳s modulus was 2.06MPa with a minimum of 1.31MPa for C7 and maximum of 2.46MPa for C5. CONCLUSIONS The values of the denticulate ligament failure force in samples from different cervical vertebrae levels differ significantly. The presented data should be taken into consideration during numerical modelling of the human cervical spinal cord.

Application of diffusion tensor imaging in the prognosis of outcome after traumatic cervical spinal cord injury

Context: The Diffusion Tensor Imaging (DTI) is a modality of the MRI describing the integrity white matter tracts of the neural tissue by mean of fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Aims: The aim of the study is to assess the usefulness of DTI in the acute assessment of patients after cervical tSCI. Settings and Design: Pilot prospective control-matched non-randomised experimental study. Materials and Methods: Five cervical tSCI patients were prospectively enrolled into the study. Neurological examination was followed by the MRI scan with DTI FA and ADC of the injured segments of the cervical spine. Obtained values were compared to the reference (healthy volunteers) by mean of statistical analysis. Statistical Analysis Used: SPSS 21.0 and MedCalc 12 software; non-parametric Spearmans rank correlation was used. The significance level was established as P < .05. Results: The FA correlated negatively with the ASIA motor score (-0.90, P = 0.037) and severity of neurological deficits (ASIA type A-E) (-0.95, P = 0.014). The ADC was positively correlated with ASIA motor score for upper limbs (0.86, P = 0.046). Two patients found with ADC higher than the reference presented early neurological recovery. Conclusions: DTI appears to be useful in the early assessment of tSCI. The FA reflects functional status of the spinal cord whilst ADC may serve a potential prognosticator.

Bilateral chronic subdural haematomas in a patient with meningioma of the superior sagittal sinus - case report and pathophysiological study.

Bilateral chronic subdural haemorrhage accompanying meningioma is a very rare clinical condition. We present a case of a 69-year-old female patient with large meningioma completely obliterating the posterior third part of the superior sagittal sinus with accompanying bilateral chronic subdural haematomas. Three anatomical zones of venous collateral circulation were revealed by the preoperative digital subtraction angiography. The tumour and haematomas were removed completely with no major complications. The most likely pathomechanism of the development of bilateral chronic subdural haematomas was venous hypertension caused by an occlusion of major cerebral venous trunks. As a result of a minor thrombotic incident or insignificant head injury, the distended veins of collateral circulation that were volumetrically burdened could have been damaged. Patients with large tumours occluding the superior sagittal sinus, who did not qualify for or refused surgery, should be carefully monitored clinically and neuroradiologically because of possibly increased risk of an intracranial haemorrhage.