Autologous olfactory ensheathing cell transplantation in human paraplegia: a 3-year clinical trial.

Olfactory ensheathing cells show promise in preclinical animal models as a cell transplantation therapy for repair of the injured spinal cord. This is a report of a clinical trial of autologous transplantation of olfactory ensheathing cells into the spinal cord in six patients with complete, thoracic paraplegia. We previously reported on the methods of surgery and transplantation and the safety aspects of the trial 1 year after transplantation. Here we address the overall design of the trial and the safety of the procedure, assessed during a period of 3 years following the transplantation surgery. All patients were assessed at entry into the trial and regularly during the period of the trial. Clinical assessments included medical, psychosocial, radiological and neurological, as well as specialized tests of neurological and functional deficits (standard American Spinal Injury Association and Functional Independence Measure assessments). Quantitative test included neurophysiological tests of sensory and motor function below the level of injury. The trial was a Phase I/IIa design whose main aim was to test the feasibility and safety of transplantation of autologous olfactory ensheathing cells into the injured spinal cord in human paraplegia. The design included a control group who did not receive surgery, otherwise closely matched to the transplant recipient group. This group acted as a control for the assessors, who were blind to the treatment status of the patients. The control group also provided the opportunity for preliminary assessment of the efficacy of the transplantation. There were no adverse findings 3 years after autologous transplantation of olfactory ensheathing cells into spinal cords injured at least 2 years prior to transplantation. The magnetic resonance images (MRIs) at 3 years showed no change from preoperative MRIs or intervening MRIs at 1 and 2 years, with no evidence of any tumour of introduced cells and no development of post-traumatic syringomyelia or other adverse radiological findings. There were no significant functional changes in any patients and no neuropathic pain. In one transplant recipient, there was an improvement over 3 segments in light touch and pin prick sensitivity bilaterally, anteriorly and posteriorly. We conclude that transplantation of autologous olfactory ensheathing cells into the injured spinal cord is feasible and is safe up to 3 years of post-implantation, however, this conclusion should be considered preliminary because of the small number of trial patients.

Autologous olfactory ensheathing cell transplantation in human spinal cord injury.

Olfactory ensheathing cells transplanted into the injured spinal cord in animals promote regeneration and remyelination of descending motor pathways through the site of injury and the return of motor functions. In a single-blind, Phase I clinical trial, we aimed to test the feasibility and safety of transplantation of autologous olfactory ensheathing cells into the injured spinal cord in human paraplegia. Participants were three male paraplegics, 18-55 years of age, with stable, complete thoracic injuries 6-32 months previously, with stable spinal column, no implanted prostheses, and no syrinx. Olfactory ensheathing cells were grown and purified in vitro from nasal biopsies and injected into the region of damaged spinal cord. The trial design includes a matched injury group as a control for the assessors, who are blind to treatment status. Assessments, made before transplantation and at regular intervals subsequently, include MRI, medical, neurological and psychosocial assessments, and standard American Spinal Injury Association and Functional Independence Measure assessments. One year after cell implantation, there were no medical, surgical or other complications to indicate that the procedure is unsafe. There is no evidence of spinal cord damage nor of cyst, syrinx or tumour formation. There was no neuropathic pain reported by the participants, no change in psychosocial status and no evidence of deterioration in neurological status. Participants will be followed for 3 years to confirm long-term safety and to compare neurological, functional and psychosocial outcomes with the control group. We conclude transplantation of autologous olfactory ensheathing cells into the injured spinal cord is feasible and is safe up to one year post-implantation.

Rapid fluctuations in conscious state in a patient with an extensive spinal dural fistula.

A man with a spontaneous spinal dural fistula and significant fluctuations in level of consciousness is discussed. The presentation was that of headache and vomiting followed by an initially enigmatic acute reduction in the level of consciousness. This required urgent evacuation of bilateral chronic subdural haematomas, believed to be causative. Following mobilisation, several episodes of presumed orthostatic intracranial hypotension occurred rendering the patient rapidly unconscious. A large spinal extradural CSF collection extending through the full length of the vertebral canal was later diagnosed however, the precise location of the fistulous leak could not be found radiologically. Non-operative management was successful. To the best of our knowledge, this is the first description of a spontaneous spinal cerebrospinal fluid leak of this magnitude. The case, pathogenesis, investigations and management of this rare entity are considered and the literature reviewed.

CSF spectrophotometry in the diagnosis and exclusion of spontaneous subarachnoid haemorrhage.

AIMS: To assess the sensitivity and specificity of CSF spectrophotometry for the detection of xanthochromia in patients with clinical symptoms suggestive of subarachnoid haemorrhage (SAH) but normal cranial computed tomography (CT). METHODS: All consecutive patients undergoing both cranial CT and lumbar puncture for investigation of possible SAH at the Princess Alexandra Hospital, Brisbane, between January 2000 and April 2003 were included in the study. All case histories, radiology and laboratory results were retrospectively assessed. The sensitivity, specificity and positive predictive value of the spectrophotometry test were calculated. RESULTS: 253 patients were included in the study. Spectrophotometry was shown to have a sensitivity of 100% but a specificity of only 75.2%. The positive predictive value of spectrophotometry as an indicator of SAH was 3.3%. CONCLUSIONS: CSF spectrophotometry has an unacceptably low specificity and positive predictive value, which greatly limit its use as a clinical tool.

The neurosurgery workforce in Australia and New Zealand: a report.

The most recent review of the neurosurgical workforce in Australasia was produced in 1992. Regular update of statistics is necessary, particularly in response to recent political trends. A survey of all neurosurgeons both resident in Australasia and overseas was undertaken. The questionnaire focussed on four main areas: surgeon distribution; workload; activity breakdown; and surgeon: patient ratio calculation. Most surgeons live in New South Wales and Victoria, as expected. Following the recommendation of the Neurosurgical Society of Australasia, Australia currently has correct numbers of surgeons, however individual states vary widely. There are few subspecialty neurosurgeons in Australasia and almost all devote the vast majority of their time to clinical work. General work force issues are examined including future requirements with respect to population changes.

Modelling the muscles of the scapula morphometric and coordinate data and functional implications.

Modelling of the shoulder mechanism is dependent upon reliable data on the morphometry and points of attachment of the relevant muscles. In this paper, the authors present coordinate data which have been derived from the radiography of dissected cadavers. All of the coordinates have been normalised with respect to reference dimensions of the relevant segments (humerus, scapula, clavicle and trunk). Similarly the measurements of physiological cross-section area (PCSA) have been normalised with respect to that of deltoid. The measurements of PCSA have been shown to agree largely with the work of Veeger et al. [J. Biomechanics 24, 615-629 (1991)] and Karlsson and Peterson [J. Biomechanics 25, 189-199 (1992)]. While the majority of the descriptions of morphometry concur with accepted texts there are some notable disagreements, particularly concerning trapezius.

Anatomy and actions of the trapezius muscle.

Dissection studies revealed the fascicular anatomy of the trapezius. Its occipital and nuchal fibres passed downwards but mainly transversely to insert into the clavicle. Fibres from C7 and T1 passed transversely to reach the acromion and spine of the scapula. Its thoracic fibres converged to the deltoid tubercle of the scapula. Volumetric studies demonstrated that the fibres from C7, T1, and the lower half of ligamentum nuchae were the largest. The essentially transverse orientation of the upper and middle fibres of trapezius precludes any action as elevators of the scapula as commonly depicted. Rather the action of these fibres is to draw the scapula and clavicle backwards or to raise the scapula by rotating the clavicle about the sternoclavicular joint. By balancing moments the trapezius relieves the cervical spine of compression loads.

Cervical zygapophyseal joints: geometrical parameters and relationship to cervical kinematics.

The relationship was examined between the height and slope of the cervical zygapophyseal joints and the patterns of motion of the cervical vertebrae. The height and orientation of the C3C7 superior articular processes were measured in lateral radiographs of 40 normal subjects. The C4-C6 facets were oriented at approximately 40° to the vertical, while the C3 and C7 facets were more steeply oriented. The heights of the superior articular processes were found to increase at progressively lower vertebral levels. Contrary to published views, the slope of the superior articular facets has no bearing on the pattern of motion of the cervical vertebrae. No relationship was found between slope of the facets and the location of the instantaneous axes of rotation of the cervical vertebrae. In contrast the height of the articular processes was perfectly related to the location of the axes of rotation. Articular height, but not slope, is a major determinant of the patterns of motions of the cervical vertebrae. This study provides data necessary to confirm or deny the putative roles of the cervical zygapophyseal joints in determining motion of the cervical spine in the sagittal plane.