Informing patient contacts about iatrogenic Creutzfeldt-Jakob disease.

The unanticipated diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) in a patient after previous neurosurgery can lead to difficult decisions regarding informing contacts. A patient developed sCJD 3 years after neurosurgery. There were 29 potential contacts and 26 were contacted. Twelve completed a questionnaire. The majority of patients wished to know about the contact and to be seen face-to-face, and their main concern was developing the disease despite verbal and written reassurance that this was unlikely. Informing patients of sCJD contact is difficult and can lead to significant patient anxiety. Face-to-face meetings, a helpline and follow-up can help.

A lumped-parameter model of the cerebrospinal system for investigating arterial-driven flow in posttraumatic syringomyelia.

Fluid transport in syringomyelia has remained enigmatic ever since the disease was first identified some three centuries ago. However, accumulating evidence in the last decade from animal studies implicates arterial pulsations in syrinx formation. In particular, it has been suggested that a phase difference between the pressure pulse in the spinal subarachnoid space and the perivascular spaces, due to a pathologically disturbed cerebrospinal fluid (CSF) or blood supply, could result in a net influx of CSF into the spinal cord (SC). A lumped-parameter model is developed of the cerebrospinal system to investigate this conjecture. It is found that although this phase-lag mechanism may operate, it requires the SC to have an intrinsic storage capacity due to the collapsibility of the contained venous reservoir. This net flux is associated with a higher mean pressure in the SC than the SSS which is maintained in the periodic steady state. According to our simulations the mechanical perturbations of arachnoiditis exacerbate the phase-lag effect, which may be partially alleviated by the presence of a posttraumatic syrinx and more completely by a syringo-subarachnoid shunt.

The pathogenesis of syringomyelia: a re-evaluation of the elastic-jump hypothesis.

Syringomyelia is a disease in which fluid-filled cavities, called syrinxes, form in the spinal cord causing progressive loss of sensory and motor functions. Invasive monitoring of pressure waves in the spinal subarachnoid space implicates a hydrodynamic origin. Poor treatment outcomes have led to myriad hypotheses for its pathogenesis, which unfortunately are often based on small numbers of patients due to the relative rarity of the disease. However, only recently have models begun to appear based on the principles of mechanics. One such model is the mathematically rigorous work of Carpenter and colleagues (2003, "Pressure Wave Propagation in Fluid-Filled Co-Axial Elastic Tubes Part 1: Basic Theory," ASME J. Biomech. Eng., 125(6), pp. 852-856; 2003, "Pressure Wave Propagation in Fluid-Filled Co-Axial Elastic Tubes Part 2: Mechanisms for the Pathogenesis of Syringomyelia," ASME J. Biomech. Eng., 125(6), pp. 857-863). They suggested that a pressure wave due to a cough or sneeze could form a shocklike elastic jump, which when incident at a stenosis, such as a hindbrain tonsil, would generate a transient region of high pressure within the spinal cord and lead to fluid accumulation. The salient physiological parameters of this model were reviewed from the literature and the assumptions and predictions re-evaluated from a mechanical standpoint. It was found that, while the spinal geometry does allow for elastic jumps to occur, their effects are likely to be weak and subsumed by the small amount of viscous damping present in the subarachnoid space. Furthermore, the polarity of the pressure differential set up by cough-type impulses opposes the tenets of the elastic-jump hypothesis. The analysis presented here does not support the elastic-jump hypothesis or any theory reliant on cough-based pressure impulses as a mechanism for the pathogenesis of syringomyelia.

The origins of syringomyelia: numerical models of fluid/structure interactions in the spinal cord.

A two-dimensional axi-symmetric numerical model is constructed of the spinal cord, consisting of elastic cord tissue surrounded by aqueous cerebrospinal fluid, in turn surrounded by elastic dura. The geometric and elastic parameters are simplified but of realistic order, compared with existing measurements. A distal reflecting site models scar tissue formed by earlier trauma to the cord, which is commonly associated with syrinx formation. Transients equivalent to both arterial pulsation and percussive coughing are used to excite wave propagation. Propagation is investigated in this model and one with a central canal down the middle of the cord tissue, and in further idealized versions of it, including a model with no cord, one with a rigid cord, one with a rigid dura, and a double-length untapered variant of the rigid-dura model. Analytical predictions for axial and radial wave-speeds in these different situations are compared with, and used to explain, the numerical outcomes. We find that the anatomic circumstances of the spinal cerebrospinal fluid cavity probably do not allow for significant wave steepening phenomena. The results indicate that wave propagation in the real cord is set by the elastic properties of both the cord tissue and the confining dura mater, fat, and bone. The central canal does not influence the wave propagation significantly.

Quantification of tumour response to radiotherapy.

In 1979, the World Health Organization (WHO) established criteria based on tumour volume change for classifying response to therapy as (i) progressive disease (PD), (ii) partial recovery (PR), and (iii) no change (NC). Typically, the tumour volume is reported from diameter measurements, using the calliper method. Alternatively, the Cavalieri method provides unbiased volume estimates of any structure without assumptions about its shape. In this study, we applied the Cavalieri method in combination with point counting to investigate the changes in tumour volume in four patients with high grade glioma, using 3D MRI. In particular, the volume of tumour within the enhancement boundary, the enhancing abnormality (EA), was estimated from T(1) weighted images, and the volume of the non-enhancing abnormality, (NEA) enhancing abnormality, was estimated from T(2) relaxation time and magnetic transfer ratio tissue characterization maps. We compared changes in tumour volume estimated by the Cavalieri method with those obtained using the calliper method. Absolute tumour volume differed significantly between the two methods. Analysis of relative change in tumour volume, based on the WHO criteria, provided a different classification using the calliper and Cavalieri methods. The benefit of the Cavalieri method over the calliper method in the estimation of tumour volume is justified by the following factors. First, Cavalieri volume estimates are mathematically unbiased. Second, the Cavalieri method is highly efficient under an appropriate sampling density (i.e. EA volume estimates can be obtained with a coefficient of error no higher than 5% in 2-3 min). Third, the source of variation of the volume estimates due to disagreements between observers, and within observer, is much greater in the positioning of the calliper diameters than in the identification of the tumour boundaries when applying the Cavalieri method. Additionally, the error prediction formula, available to estimate the coefficient of error of Cavalieri volume estimates from the data, allows us to establish more precise classification criteria against which to identify potentially clinical significant changes in tumour volume.

Syringomyelia and the arachnoid web.

Three cases of syringomyelia associated with arachnoid webs are reported. Each patient presented with progressive myelopathy and had thoracic syringes detected on magnetic resonance imaging (MRI). In one patient the web was also visible. At operation a thoracic arachnoid web was found, obstructing the subarachnoid compartment in each patient. One patient had intraoperative ultrasound, which demonstrated caudal web movement with each cardiac systole. The webs were divided and shunts inserted into the syringes. All patients improved clinically, and on follow-up MRI. Arachnoid webs are likely to represent a focal band of arachnoiditis and are difficult to visualise on standard preoperative MR imaging. A reduction in the subarachnoid space compliance with resultant increase in pulse pressure and potentiation of an arterial pulsation driven perivascular flow could explain the associated syringes. Treatment should be aimed at restoring compliance, and involve division of the web with or without shunt insertion.

Post-traumatic syringomyelia: a review.

More than a quarter of spinal cord injured patients develop syringes and many of these patients suffer progressive neurological deficits as a result of cyst enlargement. The mechanism of initial cyst formation and progressive enlargement are unknown, although arachnoiditis and persisting cord compression with disturbance of cerebrospinal fluid flow appear to be important aetiological factors. Current treatment options include correction of bony deformity, decompression of the spinal cord, division of adhesions, and shunting. Long-term improvement occurs in fewer than half of patients treated. Imaging evidence of a reduction in syrinx size following treatment does not guarantee symptomatic resolution or even prevention of further neurological loss. A better understanding of the causal mechanisms of syringomyelia is required to develop more effective therapy.

Intraspinal oxidised cellulose (Surgicel) causing delayed paraplegia after thoracotomy--a report of three cases.

Oxidised regenerated cellulose (Surgicel) is a commonly used haemostatic agent in neurosurgery, thoracic surgery, and orthopaedics. We present three cases of paraplegia after thoracic surgery during which oxidised cellulose had been used during thoracotomy for haemorrhage control, and was later found to have passed through the intervertebral foramen causing spinal cord compression. In all intraspinal and perispinal procedures, the over-liberal use of Surgicel should be avoided, and attempts made to remove all excess Surgicel once adequate haemostasis is obtained.

Some inhibitory neurons in the spinal cord develop c-fos-immunoreactivity after noxious stimulation.

In order to determine which types of spinal neuron produce c-fos in response to noxious stimulation, we have combined pre-embedding detection of c-fos-like immunoreactivity with post-embedding immunocytochemistry using antibodies against GABA and glycine, 2 h after subcutaneous injection of formalin into a hindpaw of anaesthetized rats. Throughout the spinal cord, the majority of c-fos-immunoreactive neurons (72-81%) did not possess GABA- or glycine-like immunoreactivity, while the remaining cells contained one or both types of immunoreactivity. In the superficial dorsal horn (laminae I and II) and dorsal white matter, between 14 and 20% of c-fos-immunoreactive neurons were GABA-immunoreactive, and some of these were also glycine-immunoreactive. A single neuron in lamina I in one animal was glycine- but not GABA-immunoreactive. In the remainder of the spinal cord, between 21 and 35% of the c-fos-immunoreactive cells were GABA- or glycine-immunoreactive, and the majority of these neurons contained both types of immunoreactivity. These results suggest that some inhibitory neurons in both the superficial and deep parts of the dorsal horn are activated by noxious stimuli. It is known that some of the cells which produce c-fos in response to noxious stimulation are projection neurons, with axons ascending to the brainstem or thalamus, however, because of the large number of c-fos-immunoreactive cells in the dorsal horn, it is likely that many are interneurons, and some of these are probably excitatory cells which use glutamate as a transmitter. It therefore appears that after noxious stimulation c-fos is produced in several types of spinal neuron, including projection cells and both excitatory and inhibitory interneurons.

Glutamate as the Principal Mossy Fibre Transmitter in Rat Cerebellum: pharmacological evidence.

To examine the possibility that glutamate may be widely used as the transmitter for cerebellar mossy fibres, population responses of granule cells following electrical stimulation of these fibres were recorded in rat cerebellar slices using a gap technique. Several different vermal lobules (II, V, VIb, VIII, IXc and X) whose main mossy fibre afferents originate in different nuclei, were compared. The mossy fibre response was remarkably similar in appearance in all lobules. With 1.2 mM Mg2+ in the perfusing solution, and with a low rate of stimulation (0.05 Hz), the N-methyl-D-aspartate (NMDA) antagonist, D-2-amino-5-phosphonovalerate (APV, 30 microM), had little or no effect but all components of the response could be inhibited by the broad spectrum excitatory amino acid antagonist, kynurenate (3 mM), or by the relatively selective non-NMDA antagonist, 6-cyano-2,3-dihydroxy-7-nitro-quinoxaline (CNQX, 10 microM). Slow APV-sensitive components emerged during high frequency stimulation (30 - 150 Hz) or, with a low stimulation rate, on removal of Mg2+ or addition of bicuculline (30 microM). The results suggest that an excitatory amino acid, presumably glutamate, is the major mossy fibre transmitter in the cerebellum and that it activates both NMDA and non-NMDA receptors on granule cells.

Synaptic activation of N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors in the mossy fibre pathway in adult and immature rat cerebellar slices.

The participation of excitatory amino acid receptors in mossy fibre-granule cell synapses in lobule VIa of adult and immature rat cerebellar slices was investigated using an extracellular grease-gap technique. For the immature slices, the age selected (14 days after birth) was one at which the sensitivity of granule cells to exogenous N-methyl-D-aspartate is much higher than in the adult. The principal synaptic potentials observed after low-frequency electrical stimulation of the white matter resembled closely those found to be centred in the granule cell layer in field potential studies in the cat in vivo. They comprised a short latency negative potential, a slow negative wave and, in the adult, a further late negative wave. In the adult, with 1.2 mM Mg2+ in the perfusing solution, none of these potentials was significantly affected by the N-methyl-D-aspartate antagonist, 2-amino-5-phosphonovalerate, but they were all markedly inhibited by the broad spectrum antagonist, kynurenate, and, more potently, by the selective non-N-methyl-D-aspartate receptor blocker, 6-cyano-2,3-dihydroxy-7-nitro-quinoxaline. After removal of Mg2+, which has a blocking action on the ion channels associated with N-methyl-D-aspartate receptors, the size of all the potentials increased. The increase in the short latency potential was insensitive to 2-amino-5-phosphonovalerate but a component of the slow negative wave (and of the late negative wave) was reduced back to control levels by the antagonist. Application of 6-cyano-2,3-dihydroxy-7-nitro-quinoxaline (10 microM) in Mg2+-free solution revealed, in near isolation, a slow wave (latency to peak, 28 ms) which could be abolished by 2-amino-5-phosphonovalerate. In the immature slices, bathed in normal (Mg2+-containing) medium, 2-amino-5-phosphonovalerate caused a small reduction in the short latency potential and inhibited a component of the slow negative wave which could, again, be observed in relative isolation after perfusion of 6-cyano-2,3-dihydroxy-7-nitro-quinoxaline. Removal of Mg2+ increased the amplitudes of the short latency potential and the slow negative wave in a manner which was sensitive to 2-amino-5-phosphonovalerate and increased the size of the slow, 6-cyano-2,3-dihydroxy-7-nitro-quinoxaline-resistant wave. It is concluded that glutamate is likely to be the transmitter released by mossy fibres, at least those innervating lobule VIa.(ABSTRACT TRUNCATED AT 400 WORDS)