Introduction: Post-traumatic syringomyelia produces a significant burden of pain and neurological deficits for patients with spinal cord injury. The mechanism of syrinx formation is unknown and treatment is often ineffective. Previous studies have demonstrated that fluid flow enters syrinxes from the subarachnoid space via perivascular spaces, however other pathways may be involved. It has been proposed that a damaged blood-spinal cord barrier (BSCB) provides another pathway for fluid to enter syrinxes. The purpose of this study was to investigate whether or not the integrity of the BSCB is compromised in an animal model of post-traumatic syringomyelia, and if so, whether this deficiency plays a role in the induction or subsequent enlargement of a syrinx.

Methods: The excitotoxic amino acid and arachnoiditis model of syringomyelia was used to study the structural and functional integrity of the BSCB in 27 Sprague-Dawley rats. In this model, quisqualic acid is injected into the cord to create an initial cyst. The addition of subarachnoid kaolin to create arachnoiditis results in a reliable model of syringomyelia [1]. Structural integrity of the blood-spinal cord barrier was assessed using immunoreactivity to endothelial barrier antigen (EBA) and loss of functional integrity was assessed by extravasation of intravascular horseradish peroxidise (HRP). Animals were studied at 3 days, or 1, 3, 6, or 12 weeks after surgery. There were laminectomy-only and saline injection controls at each time point.

Results: Syrinxes formed in 15 of 17 animals injected with excitotoxic amino acid. There was loss of structural and functional integrity of the BSCB in the syrinx animals at all time points. There was wide-spread disruption of the barrier at early time points, followed by recovery of the barrier except for vessels immediately adjacent to the syrinx.

Discussion: This study has demonstrated a prolonged structural and functional disruption of the BSCB. Loss of functional integrity of the barrier, with fluid entering the interstitial space of the spinal cord, may contribute to initial cyst formation after spinal cord injury and subsequent enlargement of the cyst to form post-traumatic syringomyelia.

Introduction: Enlarging cystic cavitations (syrinxes) form within the spinal cord in up to 28% of spinal cord injured patients. These post-traumatic syrinxes can cause neurological deterioration, and treatment results remain poor. Syrinxes are often found adjacent to regions of arachnoiditis.

The understanding of biological systems is increasingly dependent on modelling and simulations. Numerical simulation is not intended to replace in vivo experimental studies, but to enhance the understanding of biological systems. This study tests the hypothesis that pressure pulses in the SAS are high adjacent to areas of arachnoiditis and investigates the validity of a numerical model by comparison with in vivo experimental findings.

Methods: Experimental Model: Post-traumatic syringomyelia was induced in eight sheep by injection of kaolin into the subarachnoid space (SAS), and excitotoxic amino acid into the spinal cord of the upper thoracic spine. Cerebrospinal fluid (CSF) pressure studies were undertaken at either 3 or 6 weeks. Fibre-optic monitors were used to measure the pressure in the SAS 1 cm rostral and 1 cm caudal to the induced arachnoiditis.

Numerical Model: An axisymmetric fluid-structure interaction model was developed to represent the spinal cord and SAS under normal physiological conditions and in the presence of arachnoiditis. Arachnoiditis was modeled as a porous obstruction in the SAS.

Results: In both models the SAS pressure rostral to the arachnoiditis was found to be higher than the caudal SAS pressure. There was no statistically significant difference between the sheep at 3 and 6 weeks. Under normal conditions, both experimentally and in the numerical model, the pressure drop along the SAS was negligible. In the presence of arachnoiditis, the pressure drop across the arachnoiditis in the experimental model was 1.6 mmHg, whereas the numerical model predicted a pressure difference of 1.3 mmHg.

Discussion: The numerical model accurately predicts CSF pressures in the animal model under both normal and abnormal conditions, allowing predictions to be made to within 20% accuracy. The local increases in SAS CSF pressure demonstrated may act to increase fluid flow through perivascular spaces and be implicated in syrinx formation and enlargement.

Introduction: Apoptosis has been observed following experimental contusive and transective spinal cord injury, but it is not known whether this is related to secondary excitotoxic injury or other factors. This study examines apoptosis after a purely excitotoxic injury and the relationship between apoptosis and syrinx formation.

Methods: Twenty-four male Sprague-Dawley rats were divided into six groups. Twenty rats received four 0.5 μL injections of 24 mg/mL quisqualic acid and 1% Evans blue between the rostral C8 and caudal T1 level. Ten microliters of 250 mg/mL kaolin were then injected into the subarachnoid space. Animals were sacrificed at 1, 5, 10, 20 and 50 days following the injections. There were 4 control animals. Spinal cord tissue was frozen and sectioned, and damaged DNA was detected immunohistochemically by using anti-single-stranded DNA monoclonal antibody. The area and density of single strand DNA were semi-quantitated.

Results: No significantly damaged DNA was found in the 1 day group. Light staining of single-stranded DNA was observed at C6, C7, T1 and T2 levels in 30% of the section area in the 5 and10 day groups. Moderate staining of damaged DNA occurred at C7 and T1 levels in 25–30% of the section area at 20 day group. Syrinxes formed in this group. Heavy staining and larger syrinxes were noted in the 50 day group.

Discussion: Apoptosis increased with time after excito-toxic injury. These findings suggest that apoptosis may play a pivotal role in syrinx pathogenesis.

Introduction: It has been suggested that arachnoiditis predisposes to post-traumatic syringomyelia formation by obstructing subarachnoid cerebrospinal fluid flow and enhancing perivascular flow into the cord. In an animal model of post-traumatic syringomyelia (PTS), fluid flow in spinal cord perivascular spaces (PVS) is greater at the level of arachnoiditis and syrinx than at other levels and fluid enters the syrinx via the PVS. This study was performed to determine the effects of cerebrospinal fluid (CSF) diversion from the subarachnoid space on perivascular flow and syrinx formation in PTS.

Methods: Twenty six male Sprague-Dawley rats were investigated using the CSF tracer horseradish peroxidase (HRP), the excitotoxic and arachnoiditis model of PTS, and lumboperitoneal shunt insertion. Four experimental groups consisted of syrinx only and shunt only controls, and shunt insertion before or after syrinx formation. CSF flow studies were performed 6 weeks following the final intervention. Grading scales were used to quantify HRP staining.

Results: Syrinxes formed in all animals. Perivascular flow was greatest at the level of the syrinx. Cerebral cortex perivascular flow was significantly reduced following shunt insertion in animals with a syrinx (p< 0.05). Shunt insertion did not alter syrinx length or size, but did reduce the number of animals with evidence of sensory disturbances. There were no significant differences between shunt and syrinx first groups.

Discussion: Increasing distal subarachnoid space compliance does not affect local CSF flow into the spinal cord and syrinx. These results suggest that localised alterations in compliance, as opposed to obstruction from traumatic arachnoiditis, act as an important factor in syrinx pathogenesis.

Introduction: Post-traumatic syringomyelia typically occurs in the spinal cord adjacent to a region of arachnoiditis. This research tests the hypothesis that pressure pulses in the subarachnoid space (SAS) are higher adjacent to the arachnoiditis than in its absence. A fluid-structure interaction (FSI) analysis has been performed to study this behaviour under both normal physiological conditions and in the presence of arachnoiditis.

Method: A 2-dimensional axisymmetric cylindrical FSI model has been developed to represent the spinal cord and the SAS. CSF flow into the SAS is defined from MRI flow studies. Arachnoiditis is modelled as narrowing of the SAS. This model was based on a patient suffering from post-traumatic syringomyelia. Only the cervical region where arachnoiditis occurs has been modelled, that is from C1 to T1.

Results: Pressures in the SAS adjacent to arachnoiditis are almost 3 times higher (7.2 Pa vs. 21.67 Pa) than without arachnoiditis, with peak pressure occurring at the time of peak fluid inflow from the foramen magnum.

Discussion: The model supports the hypothesis that pressure pulses in the SAS are higher in the presence of the arachnoiditis than in normal unobstructed SAS. This elevated pressure may be implicated in syrinx formation.

INTRODUCTION: Post-traumatic syringomyelia typically occurs in the spinal cord adjacent to a region of arachnoiditis. This research tests the hypothesis that pressure pulses in the subarachnoid space (SAS) are higher adjacent to the arachnoiditis than in its absence. A fluid-structure interaction (FSI) analysis has been performed to study this behaviour under both normal physiological conditions and in the presence of arachnoiditis.

METHOD: A 2-dimensional axisymmetric cylindrical FSI model has been developed to represent the spinal cord and the SAS. CSF flow into the SAS is defined from MRI flow studies. Arachnoiditis is modelled as narrowing of the SAS. This model was based on a patient suffering from post-traumatic syringomyelia. Only the cervical region where arachnoiditis occurs has been modelled, that is from C1 to T1.

RESULTS: Pressures in the SAS adjacent to arachnoiditis are almost three times higher (7.2 Pa vs. 21.67 Pa) than without arachnoiditis, with peak pressure occurring at the time of peak fluid inflow from the foramen magnum.

DISCUSSION: The model supports the hypothesis that pressure pulses in the SAS are higher in the presence of the arachnoiditis than in normal unobstructed SAS. This elevated pressure may be implicated in syrinx formation.

INTRODUCTION: Apoptosis has been observed following experimental contusive and transective spinal cord injury, but it is not known whether this is related to secondary excitotoxic injury or other factors. This study examines apoptosis after a purely excitotoxic injury and the relationship between apoptosis and syrinx formation.

METHODS: Twenty-four male Sprague-Dawley rats were divided into six groups. Twenty rats received four 0.5 μL injections of 24 mg/mL quisqualic acid and 1% Evans blue between the rostral C8 and caudal T1 level. Ten microliters of 250 mg/mL kaolin were then injected into the subarachnoid space. Animals were sacrificed at 1, 5, 10, 20 and 50 days following the injections. There were four control animals. Spinal cord tissue was frozen and sectioned, and damaged DNA was detected immunohistochemically by using anti-single-stranded DNA monoclonal antibody. The area and density of single strand DNA were semi-quantitated.

RESULTS: No significantly damaged DNA was found in the 1 day group. Light staining of single-stranded DNA was observed at C6, C7, T1 and T2 levels in 30% of the section area in the 5 and 10 day groups. Moderate staining of damaged DNA occurred at C7 and T1 levels in 25–30% of the section area at 20 day group. Syrinxes formed in this group. Heavy staining and larger syrinxes were noted in the 50 day group.

DISCUSSION: Apoptosis increased with time after excitotoxic injury. These findings suggest that apoptosis may play a pivotal role in syrinx pathogenesis.

INTRODUCTION: It has been suggested that arachnoiditis predisposes to post-traumatic syringomyelia formation by obstructing subarachnoid cerebrospinal fluid flow and enhancing perivascular flow into the cord. In an animal model of post-traumatic syringomyelia (PTS), fluid flow in spinal cord perivascular spaces (PVS) is greater at the level of arachnoiditis and syrinx than at other levels and fluid enters the syrinx via the PVS. This study was performed to determine the effects of cere-brospinal fluid (CSF) diversion from the subarachnoid space on perivascular flow and syrinx formation in PTS.

METHODS: Twenty six male Sprague-Dawley rats were investigated using the CSF tracer horseradish peroxidase (HRP), the excitotoxic and arachnoiditis model of PTS, and lumboperitoneal shunt insertion. Four experimental groups consisted of syrinx only and shunt only controls, and shunt insertion before or after syrinx formation. CSF flow studies were performed six weeks following the final intervention. Grading scales were used to quantify HRP staining.

RESULTS: Syrinxes formed in all animals. Perivascular flow was greatest at the level of the syrinx. Cerebral cortex perivascular flow was significantly reduced following shunt insertion in animals with a syrinx (p< 0.05). Shunt insertion did not alter syrinx length or size, but did reduce the number of animals with evidence of sensory disturbances. There were no significant differences between shunt and syrinx first groups.

DISCUSSION: Increasing distal subarachnoid space compliance does not affect local CSF flow into the spinal cord and syrinx. These results suggest that localised alterations in compliance, as opposed to obstruction from traumatic arachnoiditis, act as an important factor in syrinx pathogenesis.