Spinal Syrinx Due to Lipiodol-Induced Arachnoiditis.

We present a case of a progressive symptomatic intramedullary cyst, diagnosed decades after Lipiodol injection. Lipiodol was originally administered intrathecally for the radiologic diagnosis of spinal masses. A link between the lesion and the history of Lipiodol injection was never suspected. Surgical exploration revealed a membrane above the lesion, separating the intradural space in a cranial and caudal compartment. On the level of the cyst, we identified glassy pearls containing a fatty liquid, compatible with Lipiodol deposits. We hypothesize that the syrinx is secondary to the impact of cerebrospinal fluid pulsations on the reactive membrane and that this membrane originated from an arachnoiditis caused by Lipiodol deposits. Lipiodol was indeed abandoned after it was found to cause arachnoiditis and neurologic sequelae. Despite the cessation of its usage, the causal role of Lipiodol in arachnoiditis and spinal cyst formation should still be considered, as symptoms may arise many years after Lipiodol administration.

Iophendylate myelography induced thoracic arachnoiditis, arachnoid cyst and syrinx, four decades later.

Iophendylate (Myodil) was a popular oil-based contrast agent used until late 1980s for myelography, ventriculography and cisternography. Although several long-term sequelae have been reported in literature, they are extremely rare. We report a rare occurrence of symptomatic dorsal arachnoid cyst 40 years after Myodil myelography.

Syringomyelia caused by intrathecal remnants of oil-based contrast medium.

Oily contrast medium had been in use since the early 19th century as a radiographic agent for detecting spinal lesions and spinal cord tumors until the late 20th century. At that point computed tomography scanning and magnetic resonance imaging, or other hydrophilic contrast medium substituted for it. Adverse effects of oil-based dye, both acute and chronic, had been reported since the middle of the 20th century. In this paper the authors report the case of syringomyelia that seemed to be caused mainly by remaining oily contrast medium for 44 years. Syringomyelia secondary to adhesive arachnoiditis caused by oily contrast medium after a long period of time is well known. In the present case, however, surgery revealed only mild arachnoiditis at the level of syringomyelia as well as both solid and liquid remnants of contrast medium. Generally, cerebrospinal fluid (CSF) blockage due to an arachnoid adhesion is considered to cause syringomyelia following adhesive arachnoiditis. The authors speculated that in the present case syringomyelia was induced by a mechanism different from that in the previously reported cases; the oily contrast medium itself seems to have induced the functional block of CSF and impaired the buffer system of the intrathecal pressure. No reports on thoracic adhesive arachnoiditis and syringomyelia caused by oil-based dye referred to this mechanism in reviewing the literature.

[Expression of aquaporin 4 during development of experimential presyrinx state in rabbits].

OBJECTIVE: To investigate the expression of AQP4 during the development of presyrinx state of experimental syringomyelia in rabbits. METHODS: The experimental syringomyelia models of rabbits were established by intra-cisternal injection of Kaolin. The expression of AQP4 AQP4mRNA and the water content of upper cervical spinal cord were measured with immunohistochemistry Western blot RT-PCR and dry-wet measurement on days 1,3,7,14, and 21 after operation, respectively. RESULTS: Compared with animals of control group, the water content increased in those of Kaolin group from the 1st day (68.35%+/-0.70%), reached its peak on the 7th day (72.92%+/-0.86%), lasted to the 14th day (72.58%+/-0.55%), and then began to drop on the 21st day (70.03%+/-0.77%), while AQP-4 immunoreactive expression decreased on the 3rd day [integral optical density(IOD) 320.5+/-44.2], reached its minimum on the 7th day (IOD 258.7+/-26.5), lasted to the 14th day, and recovered partially on the 21st day approximately (IOD 321.5+/-46.1). RT-PCR found the decreasing of AQP4 mRNA coincided well with that of AQP4 immunoreactive expression in presyrinx state. The linear regression analysis indicated that expression of AQP4 and its mRNA in cervical cord had a negative correlation with the change of spinal water content (r=-0.769, P<0.01; r=-0.955, P<0.01). CONCLUSION: Downregulation of AQP4 and its mRNA expression may involve in edema formation in the presyrinx state of rabbits.

Spinal Cord Transcriptomic and Metabolomic Analysis after Excitotoxic Injection Injury Model of Syringomyelia.

Syringomyelia is a condition of the spinal cord in which a syrinx, or fluid-filled cavity, forms from trauma, malformation, or general disorder. Previous work has shown that in noncanalicular syringomyelia irregular flow and pressure conditions enhance the volumetric growth of syrinxes. A better understanding of the underlying molecular pathways associated with syrinx formation will unveil targets for treatments and possibly prevention of syringomyelia in the future. In this study, we performed an established surgical induction of a syrinx using quisqualic acid and kaolin injections in rats to characterize the injury at the molecular level by RNA sequencing and metabolomics techniques at three and six weeks post-injury. Syrinxes averaging nearly 10 mm in length formed in the rats' spinal cords; however, smaller syrinxes were also detected in saline injected surgical shams, complicating interpretation of results. Our current results indicate a robust immune response coupled with overall decreases in neuronal signal transmission of syrinx containing animals compared with controls. Although transcriptional changes indicated gliosis and loss of neurons, no neuropathic pain was detected by von Frey allodynia testing. Unique transporters were revealed to be highly dysregulated, including significant increases in betaine/glycine transporter (BGT-1), K+/Cl- co-transporter (KCC4), and aquaporin 1 (AQP1), along with the upregulation of small molecule osmolytes taurine and betaine. The identified metabolites are of particular interest because of their involvement in osmotic homeostasis and need to be investigated further for their specific involvement in trauma-induced syrinxes.

Thoracic arachnoiditis, arachnoid cyst and syrinx formation secondary to myelography with Myodil, 30 years previously.

Spinal arachnoiditis can rarely occur following irritation from foreign body substances, including certain oil based contrast agents used for myelography. We describe a patient with thoracic arachnoiditis, arachnoid cyst and syringomyelia, 30 years following a myelogram with Myodil. A 62-year-old female presented with chronic thoraco-lumbar back pain, a spastic paraparesis and sphincter disturbance. She had undergone a myelogram with Myodil, 30 years previously for investigation of back pain. A MRI scan revealed evidence of arachnoiditis, thoracic syringomyelia (T6-T8) and an anteriorly placed, extramedullary, arachnoid cyst at T10-T12, compressing the cord. At surgery, T7-T10 thoracic laminectomies were carried out and syringo- and cysto-subarachnoid shunts were inserted. At 12 months follow-up, the sphincter disturbance, lower limb weakness and mobility problems had almost resolved. Although, the use of oil based contrast agents such as Myodil has been discontinued, the present case illustrates some of the rare sequelae of its use, manifesting decades later. Aggressive surgical intervention produced symptomatic benefit.

[Effect of Ginkgo biloba extract on neuronal apoptosis in rabbit with kaolin-induced syringomyelia].

OBJECTIVE: To evaluate the effect of Ginkgo biloba extract (GBE) on neuronal apoptosis in rabbits with kaolin-induced syringomyelia. METHODS: Twenty-four of 30 Chinese white rabbits were subjected to injection of 25% kaolin mixed with equal volume (0.6 ml) of cerebrospinal fluid drawn from the cisterna magna under ketamine anesthesia. Twelve of these 24 rabbits then received intravenous injection of 5 ml of GBE (5 ml/days for 14 days, GBE treatment group) while the other 12 were treated with the same amount of saline administered in similar manner (saline group). The 6 rabbits without kaolin treatment received a sham operation to serve as the control group. At different time points after the operation, the rabbits were killed and the spinal cord samples examined by immunohistochemistry. RESULTS: Histologically, ischemia and edema in the cervical cord of rabbits in GBE treatment group were less severe than those in saline group. TUNEL-positive and bax-positive neurons were less numerous in GBE treatment group than in saline group, and the former group showed more Bcl-2-positive neurons. The number of apoptotic neurons reached the peak level on day 7 after kaolin injection. CONCLUSION: GBE can ameliorate kaolin-induced hydrocephalus in the upper cervical cord and inhibit kaolin-induced neuron apoptosis.

The role of excitotoxic injury in post-traumatic syringomyelia.

Fifty percent of patients with neurological deterioration from post-traumatic syringomyelia do not respond to treatment. Treatment failure is due in part to an incomplete understanding of the underlying aetiology. An animal model that mimics the human disease is required to investigate underlying pathophysiology and treatment options. A previous study was designed to mimic trauma-induced effects on the spinal cord that result in syringomyelia, combining an excitotoxic insult with kaolin-induced arachnoiditis. In this excitotoxic model, syringes were produced in 82% of animals. The aims of the current study were to improve the model to produce syringes in all animals treated, to examine the relative influences of excitotoxic injury and neuronal loss on syrinx formation, and to use magnetic resonance imaging (MRI) to examine syringes non-invasively. A temporal and dose profile of intraparenchymal quisqualic acid (QA) and subarachnoid kaolin was performed in Sprague Dawley rats. MRI was used to study four syrinx and six control animals. In one subgroup of animals surviving for 6 weeks, 100% (eight of eight) developed syringes. Syrinx formation and enlargement occurred in a dose and time dependent manner, whilst significant neuronal loss was only dose dependent. Animal syrinx histology closely resembled human post-traumatic syringomyelia. Axial T2-weighted MR images demonstrated syrinx presence. The results suggest that the formation of an initial cyst predisposes to syrinx formation in the presence of subarachnoid adhesions.

Diffusion-weighted MR imaging in a rat model of syringomyelia after excitotoxic spinal cord injury.

BACKGROUND AND PURPOSE: Recent experimental data have shown that an increase of excitatory amino acids and the initiation of inflammatory responses within the injured spinal cord may play a role in post-traumatic syringomyelia. The purpose of this study was to determine whether diffusion-weighted MR imaging with apparent diffusion coefficient (ADC) maps could provide earlier evidence of spinal cord cavitation in a rat model of syringomyelia than available with conventional MR imaging. METHODS: The spinal cord gray matter of four rats was injected with the alpha-amino-3 hydroxy-5 methyl-4 isoxazole propionic acid/metabotropic receptor agonist quisqualic acid. Animals were sacrificed at 1, 4, or 8 weeks after injection, and the spinal cords were fixed in formalin for 1 week and imaged with T1-, T2-, and diffusion-weighted sequences. One control specimen was also imaged. ADC maps were constructed from the diffusion-weighted data. Histopathologic analyses of sections stained with cresyl violet were compared with the MR images. RESULTS: By 1 week after injection, ADC maps at the level of injection showed areas within the gray matter of increased intensity and increased ADC values as compared with the control specimen. These bright areas corresponded to cysts or cavities within the cord parenchyma on the histopathologic sections. The ADC values within affected gray matter areas progressively increased at 4 and 8 weeks, also corresponding to cyst formation. Conventional T1- and T2-weighted images showed corresponding lesions with cystic characteristics at 4 and 8 weeks, but not at 1 week. CONCLUSION: In an animal model of syringomyelia, diffusion-weighted imaging with ADC maps detected cystic lesions within spinal cord gray matter before they were seen on conventional T1- and T2-weighted images.

Experimental communicating syringomyelia in dogs after cisternal kaolin injection. Part 2. Pressure studies.

Pressure measurements in cerebrospinal fluid have been made from the ventricles and the spinal subarachnoid space in dogs made hydrocephalic by intracisternal injections of kaolin. Raised intraventricular pressure has been confirmed in the confirmed in the ventricles. The spinal pressure is usually markedly different from that in the head, confirming that the arachnoiditis produced around the cistern isolates the spinal subarachnoid space from the CSF in the head. Pulsatile pressures have been investigated specifically and the interrelationship between the pulsation and baseline pressures in the development of communicating syringomyelia discussed. There are differences between these experimental animals and the human disease, particularly in the baseline pressures which are usually equal in the head and the spine of humans at rest even in cases with syringomyelia.

Experimental communicating syringomyelia in dogs after cisternal kaolin injection. Part 1. Morphology.

Intracisternal kaolin injection in dogs usually produces hydrocephalus and out of 16 such dogs 11 have shown enlargement of the central canal of the spinal cord which has proceeded to syringomyelia-like cavities in 7 instances. The morphology of the cavities is described, the absence of ischaemic changes in the cord noted and the occasional communication of the cavities with the spinal subarachnoid space at the level of the filum terminale confirmed. The similarities to human syringomyelia are noted together with important differences in the etiology. The dogs all had arachnoiditis, all had hydrocephalus and all had a radiologically demonstrable communication of the cavities with the 4th ventricle, findings which are unusual in human syringomyelia.

A study of experimental syringomyelia by scanning electron microscopy.

Experimental hydromyelia and syringomyelia, induced by kaolin in dogs, has been investigated by scanning electron microscopy. This study demonstrated that communication between the 4th ventricle and the spinal central canal is normally occluded by a plug of acellular material lying within the central canal. This plug is broken down following the onset of hydrocephalus and communication is rapidly established between the ventricles and the central canal. The canal distends and ruptures dorsally into the spinal gray matter with the development of extensive intramedullary cavities, lined by glial and neuronal elements. The morphological changes demonstrated are consistent with a physical destructive process of the cord resulting from CSF dissection.

Cerebrospinal fluid flow in an animal model of noncommunicating syringomyelia.

OBJECTIVE: The source of fluid and the mechanism of cyst enlargement in syringomyelia are unknown. It has been demonstrated that cerebrospinal fluid (CSF) normally flows from the subarachnoid space through perivascular spaces and into the spinal cord central canal. The aim of this study was to investigate whether this flow continues during cyst formation in an animal model of syringomyelia and to determine the role of subarachnoid CSF flow in this model. METHODS: The intraparenchymal kaolin model of noncommunicating syringomyelia was established in 78 Sprague-Dawley rats. Horseradish peroxidase was used as a tracer to study CSF flow at 1 day, 3 days, 1 week, and 6 weeks after kaolin injection. CSF flow was studied at 0, 10, and 30 minutes after horseradish peroxidase injection into the cisterna magna or thoracic subarachnoid space. RESULTS: The central canal became occluded at the level of the kaolin injection and at one or more rostral levels. Segments of the central canal isolated between occlusions gradually dilated, and axonal retraction balls were detected in the surrounding white matter. There was a partial blockage of subarachnoid CSF flow at the site of the kaolin injection, both in a rostral-caudal direction and in a caudal-rostral direction. Horseradish peroxidase was detected at all time points, in a distinctive pattern, in perivascular spaces and the central canal. This pattern was seen even where segments of the central canal were isolated and dilated. CONCLUSION: In this animal model, noncommunicating syringes continue to enlarge even when there is evidence that they are under high pressure. There may be an increase in pulse pressure rostral to the block of subarachnoid CSF flow, causing an increase in perivascular flow and contributing to syrinx formation. The source of fluid in noncommunicating syringomyelia may be arterial pulsation-dependent CSF flow from perivascular spaces into the central canal.

Thoracic spinal Pantopaque cyst and associated syrinx resulting in progressive spastic paraparesis: case report.

OBJECTIVE AND IMPORTANCE: We describe a unique presentation of a thoracic spinal Pantopaque cyst. Although Pantopaque is no longer used, sequelae of its long-term use may continue to surface. CLINICAL PRESENTATION: Our patient presented to the emergency room with 4 months of progressive lower extremity numbness, spasticity, and incontinence and a 2-day history of left upper extremity dysesthesias. Magnetic resonance imaging at admission revealed a C7-T10 syrinx and an intrathecal extramedullary mass to the right of the spinal cord at T10-T11. INTERVENTION: Radiographic evidence led to the initial diagnosis of hemangioblastoma. The results of a critical analysis of the preoperative studies caused us to suspect a Pantopaque cyst. This suspicion was confirmed at the time of surgery, when a cyst filled with contrast medium was revealed. T9-T11 laminectomies were performed, allowing for a 5-cm dural opening. The cyst was aspirated and excised, and then the syrinx was decompressed. CONCLUSION: Our patient experienced significant sensory and motor improvement postoperatively. We present a previously undescribed complication of one of the most commonly used contrast media, Pantopaque. Despite its replacement with newer agents, it may continue to play a significant role in the pathological presentation of patients in whom it was previously used.

Experimental syringomyelia in the rabbit: an ultrastructural study of the spinal cord tissue.

Hydrosyringomyelia was produced experimentally by the injection of kaolin into the cisterna magna of the rabbit, and the ultrastructural changes of the spinal cord surrounding the syrinx were investigated 2, 4, and 6 weeks after injection by transmission electron microscopy. The ependyma at the ventral part of the central canal was flat and stretched, whereas, in the dorsal part, it was split, and the syrinx extended through the dorsal median plane in most animals. Extracellular edema was found in the subependymal white matter and in and around the posterior median septum. Many nerve fibers surrounding the syrinx were in varying stages of axonal degeneration. Myelin sheaths were split, thinned, and completely lost in many nerve fibers. In some fibers, the axons were totally lost, leaving the myelin sheaths as empty tubes. Astrocytic processes containing a large number of glial filaments covered the nerve fibers adjacent to the syrinx and partially replaced the edematous area. The perivascular spaces were enlarged, especially near the syrinx and in the dorsal white matter. Oligodendrocytes remained undamaged, and the remyelination by oligodendrocytic processes was seen on some denuded axons. Sometimes, this further remyelination was abortive, especially where the edema was severe. The ultrastructural changes of the neural tissue and their sequences were identical, in most respects, to those of hydrocephalus and noncommunicating syringomyelia. The oligodendrocytic remyelination with ongoing demyelination found in this model has many similarities to those in experimental hydrocephalus.

Radiosotope evaluation of experimental hydrosyringomyelia.

Kaolin-induced hydrosyringomyelia in dogs has been investigated by radioisotope ventriculography using both cerebrospinal fluid radioassay and scintigraphy. The hydromyelic central canal can be differentiated from the spinal subarachnoid space by scintigraphy, Serial studies show that hydromyelia arises rapidly to decompress the associated hydrocephalus in surviving animals. Syringomyelia, after a delayed onset, originates from the enlarged central canal. Radioisotope ventriculography may be a useful clinical aid in the diagnosis of hydrosyringomyelia.

Structural scoliosis model in dogs with experimentally induced syringomyelia.

STUDY DESIGN: Animal scoliosis model associated with syringomyelia. OBJECTIVE: To investigate the pathogenesis of scoliosis produced in dogs with kaolin-induced syringomyelia. SUMMARY OF BACKGROUND DATA: Kaolin injected into the cisterna magna produces basilar arachnoiditis, leading to hydrocephalus and syringomyelia. There have been no reports on scoliosis associated with kaolin-induced syringomyelia. METHODS: Kaolin was injected percutaneously into the cisterna magna of 11 beagles 6-8 weeks after birth. Roentgenograms, computed tomography, and magnetic resonance imaging were obtained. The spinal cord and the paraspinal muscles were examined histologically. Structural changes of the vertebral column were analyzed with calcein and tetracycline labeling. RESULTS: Hydrocephalus occurred in nine dogs. A communicating syringomyelia appeared in five dogs. Mild scoliosis developed in two dogs, and severe cervical scoliosis in one dog. In the syringomyelia cases, acute or subacute inflammatory changes were found in the spinal cord. Damage of the anterior and posterior horn cells was more marked in the scoliotic animals than in the nonscoliotic animals. In three of the syringomyelia cases, including two scoliosis cases, the paraspinal muscles revealed neurogenic changes. The deformed vertebrae appeared to diminish rather than to increase the deformity in severe scoliosis. CONCLUSION: The exact mechanism of the development of scoliosis could not be identified, although an etiologic relation with malfunction of the central nervous system was noted. This model may be useful to study scoliosis experimentally.

Excitotoxic model of post-traumatic syringomyelia in the rat.

STUDY DESIGN: A rat model was developed to elucidate the role of excitatory amino acids and spinal subarachnoid block in the genesis of post-traumatic syringomyelia. This excitotoxic model produces intramedullary cavities rather than the dilation of the central canal (canalicular syringomyelia) created by previous animal models. OBJECTIVES: To produce extracanalicular cysts in the rat spinal cord with quisqualic acid, a potent agonist of multiple excitatory amino acid receptors, and to compare the effects of excitotoxic injury only with that of excitotoxic injury and subarachnoid block with kaolin. SUMMARY OF BACKGROUND DATA: In post-traumatic syringomyelia, primary injury and excitotoxic cell death secondary to elevated levels of excitatory amino acids may initiate a pathologic process leading to the formation of spinal cavities. Subarachnoid block by arachnoiditis may promote enlargement of the cavities. METHODS: Three control rats received a unilateral injection of normal saline into the spinal cord, and another five rats received an injection of kaolin into the spinal subarachnoid space. Quisqualic acid was injected unilaterally into the spinal cord of 20 rats, and 13 additional rats received a unilateral injection of quisqualic acid into the spinal cord after injection of kaolin into the subarachnoid space. Histologic and immunocytochemical assessments were undertaken. RESULTS: In the control groups, no parenchymal cyst developed in any of the animals. Spinal cord cyst formation was observed in 16 of 19 animals in the quisqualic acid groups, but no cysts exceeding two segments in the length of the spinal cord developed in any of the rats. Much larger cavities were seen in 9 of 11 animals in the group with quisqualic acid and kaolin, and cysts exceeding two segments developed in all 9 of these (9/11; 82%). CONCLUSIONS: In post-traumatic syringomyelia, excitotoxic cell death occurring secondarily to elevated levels of excitatory amino acids may contribute to the pathologic process leading to the formation of spinal cord cysts. Subarachnoid block by arachnoiditis is likely to cause enlargement of the cavity.

Experimental syringomyelia: late ultrastructural changes of spinal cord tissue and magnetic resonance imaging evaluation.

BACKGROUND: In human hydrosyringomyelia and in the late stage of experimental syringomyelia, the spinal cord tissue adjacent to the syrinx is exposed to a similar pathophysiologic condition. We investigated the ultrastructural changes in the late stages of kaolin-induced syringomyelia, and in addition, we presented magnetic resonance imaging (MRI) findings of the cervicomedullary junction and syrinx, and the nature of edema in the spinal cord of this experimental model. METHODS: Syringomyelia was induced in rabbits by intracisternal injection of kaolin. MRI was performed at 6 weeks, and 6 and 12 months following injection, and the animals were killed by transcardial perfusion of formaldehyde solution and examined by transmission electron microscopy. Evans blue was injected intravenously in six rabbits, 6 weeks and 12 months following kaolin injection and was examined by confocal laser scanning microscopy. RESULTS: MRI showed that the syrinx communicated with the fourth ventricle in most animals. Demyelination of varying degrees and slight edematous change were seen in the perisyrinx white matter. No extravasation of Evans blue was seen by confocal microscopy. Abundant astrocytic proliferation with a large number of glial filaments was seen at the margin of the syrinx and between the axons in the perisyringeal region. The perivascular space enlargement occurred in both the gray and white matter. The endothelial junctions appeared intact. Regenerating axons and remyelination by oligodendrocytes were seen occasionally. CONCLUSIONS: The MRI confirmed the communication between the fourth ventricle and the syrinx. The ultrastructural changes were almost identical to those of the early stage syrinx, but the astrocytic proliferation was more severe, and the edema was less in the late stage. The perisyrinx edema appeared to be of the interstitial type, as in hydrocephalus. Axonal degeneration and demyelination continued with abortive attempt at regeneration and remyelination in the less edematous late stage, which might be the cellular basis for the persistence or worsening of clinical symptoms and signs in the chronic stage of syringomyelia even after surgical treatment.