The pathogenesis of syringomyelia associated with lesions at the foramen magnum: a critical review of existing theories and proposal of a new hypothesis

Syringomyelia is frequently accompanied by an extramedullary lesion at the foramen magnum, particularly a Chiari I malformation. Although syringomyelia associated with foramen magnum obstruction has characteristic clinical, radiological, and neuropathological features, its pathogenesis remains unclear. Currently prevalent hydrodynamical theories assert that obstruction of the subarachnoid space at the foramen magnum interferes with flow of cerebrospinal fluid (CSF) between the spinal and the intracranial subarachnoid compartments. As a result, spinal CSF is driven into the spinal cord through the perivascular spaces to form a syrinx. These theories are implausible biophysically because none postulates a pump adequate to drive fluid through these spaces. None of the theories can explain why syrinx pressure is higher than CSF pressure; why extensive gliosis, edema, and vascular wall thickening regularly occur; and why the composition of syrinx fluid is not identical with that of CSF.

A new theory of pathogenesis is proposed to address these difficulties. In the presence of subarachnoid obstruction at the foramen magnum, a variety of activities, such as assuming the erect posture, coughing or straining, and pulsatile fluctuations of CSF pressure during the cardiac cycle, produce transiently higher CSF pressure above the block than below it. There are corresponding changes in transmural venous and capillary pressure favoring dilation of vessels below the block and collapse of vessels above the block. The spatially uneven change of vessel caliber produces mechanical stress on the spinal cord, particularly caudal to the block. The mechanical stress, coupled with venous and capillary dilation, partially disrupt the blood–spinal cord barrier, allowing ultrafiltration of crystalloids and accumulation of a protein-poor fluid.

The proposed theory is consistent with the neuropathological findings in syringomyelia and with the pressure and composition of syrinx fluid. It also accounts for the prolonged course of syringomyelia and its aggravation by cough, strain, and assumption of an erect posture. It contributes to understanding the low incidence and the morphology of syringobulbia. It explains the poorly understood presentation of foramen magnum meningiomas with symptoms of a mid- to low-cervical myelopathy. The theory also affords an understanding of the late recurrence of symptoms in children with hydromyelia who are treated with a ventricular shunt.     

Syringomyelia and arachnoiditis.

Five patients with chronic arachnoiditis and syringomyelia were studied. Three patients had early life meningitis and developed symptoms of syringomyelia eight, 21, and 23 years after the acute infection. One patient had a spinal dural thoracic AVM and developed a thoracic syrinx 11 years after spinal subarachnoid haemorrhage and five years after surgery on the AVM. A fifth patient had tuberculous meningitis with transient spinal cord dysfunction followed by development of a lumbar syrinx seven years later. Arachnoiditis can cause syrinx formation by obliterating the spinal vasculature causing ischaemia. Small cystic regions of myelomalacia coalesce to form cavities. In other patients, central cord ischaemia mimics syringomyelia but no cavitation is present. Scar formation with spinal block leads to altered dynamics of cerebrospinal fluid (CSF) flow and contributes to the formation of spinal cord cystic cavities.     

Syringomyelia and tethered cord in children

Introduction

The presence of syringomyelia varies in patients with different forms of dysraphism; from 21 % to 67 %. Only around 60 % of patients with syringomyelia is likely to experience symptoms related to it.

Pathophysiology

Many theories have been outlined for the creation of syringomyelia. The one most applicable to tethered cord dictates that tensile radial stress may create a syrinx in a previously normal cord tissue and transiently lower pressure may draw in interstitial fluid, causing the syrinx to enlarge if fluid exit is inhibited. In addition, arachnoiditis increases flow resistance in the spinal subarachnoid space, altering temporal CSF pulse pressure dynamics, which promotes entry of CSF in to the spinal cord.

Clinical presentation

There is a significant overlap between the symptoms that are due to tethered cord and syringomyelia, both in newly presenting patients with coexisting syringomyelia, and in previously treated patients who during follow-up present recurrent symptoms and a new syringomyelia cavity.

Treatment

The treatment of patients with tethered cord and syringomyelia is directed towards untethering the cord from its most caudal region upwards and restoring spinal anatomy with reestablishment of unobstructed CSF flow in the subarachnoid space. Only if complete untethering has been ensured and syringomyelia deteriorates, then surgical treatment can be directed against the syrinx. In patients with spinal dysraphism and coexisting hydrocephalus, radiological presentation of new syringomyelia or deterioration of previously known syringomyelia may signify shunt obstruction “until proven otherwise”.

Conclusion

In most occasions, satisfactory cord untethering addresses the development of syringomyelia.     

The pathogenesis of syringomyelia in spinal cord ependymoma

A spinal cord ependymoma with syringomyelia is presented. The pathogenesis of syrinx formation, associated with intramedullary tumors is not fully understood. In order to examine the mechanism of formation of the tumor-associated syrinx, syrinx fluid was obtained during surgery and concentrations of proteins were measured in the syrinx fluid, the cerebrospinal fluid (CSF) and blood serum. Protein analysis of fluid specimens showed the fluid in tumor-associated syrinx to be an exudate. This strongly indicates that, in this case, intramedullary tumor-associated syringomyelia is based on disruption of the blood-brain barrier.     

Theoretical analysis of the pathophysiology of syringomyelia associated with adhesive arachnoiditis

OBJECTIVE: To apply a theoretical model to analyse the derangement of cerebrospinal fluid (CSF) dynamics in syringomyelia associated with adhesive arachnoiditis. METHODS: An electrical circuit model of CSF dynamics in the spine was used. With this model, the derangement of CSF dynamics in adhesive arachnoiditis was simulated. The effects of various surgical procedures were then analysed, such as syringo-subarachnoid shunting, subarachnoid bypass, and foramen magnum decompression. RESULTS: When CSF flow in the subarachnoid space was obstructed at a certain point, the pressure inside the spinal cord increased in the segment immediately distal to the blockage. This location of increased pressure corresponded to the preferred site of syrinx formation in adhesive arachnoiditis. Syringo-subarachnoid shunting, subarachnoid bypass, and foramen magnum decompression were all effective at reducing this pressure gradient. CONCLUSIONS: Blockage of the spinal subarachnoid CSF pathway produces a relative increase in the pressure inside the spinal cord distal to the blockage point. Repetitive formation of this pressure gradient then induces CSF leakage into the spinal parenchyma, leading to the formation of syringomyelia. Using this model, alternative surgical procedures could be suggested that might be effective in treating this disease.     

Syringomyelia and hydromyelia: Current understanding and neurosurgical management

Syringomyelia is a rare disorder in which a fluid-filled cyst forms within the spinal cord, resulting in myelopathy. Meanwhile, the abnormal dilatation of the central canal is referred to as hydromyelia or slit-like syrinx. The most prevailing classification is based on anatomical features and pathogeny rather than pathophysiological mechanisms. It is usual to distinguish foraminal syringomyelia related mainly to abnormalities at the craniocervical junction, non-foraminal syringomyelia dealing with any cause of arachnoiditis (infection, inflammation, trauma…) and more rarely syringomyelia associated with intramedullary tumors. Although many pathophysiological theories have been argued over time, the prevailing one is that disturbances in cerebrospinal fluid (CSF) flow in the sub-arachnoid spaces disrupt flow velocity leading to the syrinx. Symptoms of paralysis, sensory loss and chronic pain commonly develop during the third/fourth decades of life. The natural history of syringomyelia is typically one of gradual, stepwise neurological deterioration extending over many years. Diagnosis is based on magnetic resonance imaging (MRI) including excellent morphological sequences (T1-, T2-, FLAIR-, T2*-, enhanced T1-) and dynamic MRI with careful study of CSF velocity (CISS, cine-MR sequences). Surgical management is at first dedicated to treat the cause of the syringomyelia, mainly to re-establish a physiological CSF pathway in the subarachnoid spaces. Mostly, the surgical goal is to enlarge the craniocervical junction with duraplasty. Other surgical strategies such as arachnoidolysis or shunt procedures are performed based on the pathogenic mechanisms or as second-line treatment. Medical treatments are also necessary as chronic pain is the main long-lasting symptom. As evolutive syringomyelia is a severe disease with a high impact on quality of life, it is recommended to treat without delay. There is no evidence for surgery for incidental asymptomatic syringomyelia or hydromyelia. Finally, syringomyelia associated with intramedullary tumors resolves spontaneously after tumor resection. Syringomyelia is a rare disease, which requires a dedicated multidisciplinary approach, emphasizing the need for a nationwide scientific organization so as to offer optimal care to the patient.     

Syrinx size and duration of symptoms predict the pace of progressive myelopathy: retrospective analysis of 103 unoperated cases with craniocervical junction malformations and syringomyelia

OBJECTIVE: the clinical course of syringomyelia associated with craniocervical junction abnormalities is variable. About half of the unoperated patients have benign course. This is difficult to explain on the basis of the present pathogenetic theories. Therefore, to understand the mechanism of syrinx progression better, we studied the value of syrinx size, syrinx morphology, and the syrinx/spinal cord size ratio in predicting the rate of progression and the severity of myelopathy in these patients. METHODS: 103 adult patients with syringomyelia associated with Chiari 1 malformation and/or radiographic signs of underdeveloped posterior cranial fossa were clinically and MRI examined. Patients were subdivided according to the type of disease progression. Severity of neurological deficits, and MRI features (the extent of cerebellar tonsillar displacement, anteroposterior diameter of cavities, the spinal cord and cyst/cord ratio and the shape of cavities) were measured. RESULTS: a significant relationship was found between the mid-sagittal diameter of the syrinxes and the type of disease course; patients with short duration and rapid progression had the largest diameters of cavities, whereas patients with longer duration as well as with slow rate of progression had smaller diameters (chi(2)=28.90, P<0.05; chi(2)=29.89, P<0.01; r=-0.24, P<0.05). In addition, a correlation was found between the anteroposterior diameter of the spinal cord and cyst/cord ratio and the disease duration (r=0.52, P<0.05 and r=0.48, P<0.05, respectively). CONCLUSIONS: the initial years for the development of symptomatic syringomyelia associated with CCJ malformations are characterized by relatively rapid clinical progression accompanied with distended cavities. In the later periods of unoperated syringomyelia, some patients show delay in the progress of syrinxes accompanied with collapse of cavities, probably either due to a spontaneous formation of drainage between the syrinx and the subarachnoidal space, or due to the restoration of abnormal CSF dynamics at the CCJ level.     

Intraoperative measurement of spinal cord blood flow in syringomyelia

The role of spinal cord ischemia in the pathophysiology of syringomyelia remains undetermined. Previous reports in the literature suggest that shunting of syringes can improve spinal cord blood flow. In order to determine the effects of syrinx decompression on spinal cord blood flow in patients with syringomyelia, we prospectively measured regional spinal cord blood flow (RSCBF) intraoperatively pre and post shunting in patients with symptomatic syringomyelia using laser doppler flowmetry. Six patients with MRI documented syringomyelia were studied (three with Arnold Chiari I malformation and associated syrinx and three with post-traumatic syringomyelia). Surgery was performed on all patients with either a syringopleural or syringoperitoneal shunt. Laser doppler blood flow and somatosensory evoked potentials were monitored prior to myelotomy and after shunt insertion. Results indicate that there was a significant increase in RSCBF after decompression of the syrinx. This study supports the hypothesis that spinal cord ischemia is important in the pathophysiology of syringomyelia and confirms previous reports in the literature regarding RSCBF in syringomyelia.     

Hypothesis on the pathophysiology of syringomyelia based on simulation of cerebrospinal fluid dynamics

OBJECTIVES: Despite many hypotheses, the pathophysiology of syringomyelia is still not well understood. In this report, the authors propose a hypothesis based on analysis of cerebrospinal fluid dynamics in the spine. METHODS: An electric circuit model of the CSF dynamics of the spine was constructed based on a technique of computational fluid mechanics. With this model, the authors calculated how a pulsatile CSF wave coming from the cranial side is propagated along the spinal cord. RESULTS: Reducing the temporary fluid storage capacity of the cisterna magna dramatically increased the pressure wave propagated along the central canal. The peak of this pressure wave resided in the mid-portion of the spinal cord. CONCLUSIONS: The following hypotheses are proposed. The cisterna magna functions as a shock absorber against the pulsatile CSF waves coming from the cranial side. The loss of shock absorbing capacity of the cisterna magna and subsequent increase of central canal wall pressure leads to syrinx formation in patients with Chiari I malformation.     

Syringomyelia: cyst measurement by magnetic resonance imaging and comparison with symptoms, signs and disability.

The severity and distribution of symptoms and signs in patients with syringomyelia is considered to be dependent on the longitudinal and transverse dimensions of the syrinx and it is thought that clinical examination can identify the extent of the cyst. Magnetic resonance imaging has made the anatomical localisation of intramedullary spinal lesions more exact and probably more specific than previous methods of investigation. Syrinx length, diameters, cyst:cord and cord:canal ratios have been studied in 12 patients with syringomyelia to assess whether the dimensions of the syrinx relate to the clinical findings. The length of syrinx appeared to be related to cyst diameter, cyst:cord and cord:canal ratios. Patients with a small syrinx tended to have a small cyst diameter, and small cyst:cord and cord:canal ratios. No significant relationship was found between muscle wasting or weakness, distribution of sensory loss, degree of disability or distress and the dimensions of the syrinx. These findings should be borne in mind when surgical management is being considered.     

Quantitative analysis of cerebrospinal fluid dynamics in syringomyelia using cine MRI with pre-saturation]

Some reports show the qualitative analysis of cerebrospinal fluid (CSF) pulsation in the subarachnoid space and the syrinx using cine magnetic resonance imaging (MRI). However, few reports studied the quantitative analysis of CSF pulsation. We report here the results of quantitative analysis of CSF pulsation using the cine MRI with pre-saturation pulse. Using flow phantom, we calibrated the correlation between the true velocity and calculated velocity acquired from the movement of pre-saturated low signal. Three cases of syringomyelia with Chiari malformation, two cases of traumatic syringomyelia, and three normal volunteers were examined using this technique, and we could obtain time-velocity curves of CSF in both subarachnoid spaces and syrinx. Although obvious pulsation of CSF was observed in the syrinx of all Chiari malformations, no pulsation of CSF was observed in the syrinx of traumatic syringomyelia. CSF in the syrinx moves upward in the early systolic cardiac cycle, downward in the systolic cycle, and upward again in the diastolic cycle. Patterns of CSF pulsation in syrinx were similar to those in the subarachnoid space, but "phase" of these pulsations differed from case to case. These results suggest the close relationship between CSF pulsation in the syrinx and CSF obstruction at the cranio-vertebral junction. Dissociation of the "phase" of CSF pulsation in the syrinx and subarachnoid space may be significant in the analysis of the pathogenesis of syringomyelia.     

Syringomyelia in association with a neurofibroma of the filum terminale

A case of neurofibroma of the filum terminale associated with syringomyelia is described. The relationship of spinal cord tumours and syringomyelia is discussed and a possible mode of formation of the syrinx in the present case is suggested.     

Pathogenesis and the treatment of secondary syringomyelia

Six cases with secondary syringomyelia were evaluated clinically and the pathogenesis was discussed. Three cases had the tumors; an ependymoma arising from the conus medullaris and the filum terminale, a foramen magnum meningioma extending to C2 and a thoracic astrocytoma. Two cases had past history of spinal cord injury with L1 and L2 fracture-dislocation, respectively. One case showed hydromyelic symptoms associated with isolated fourth ventricle after post-meningitic hydrocephalus. Clinical symptoms and signs were complex and various in each case due to the association of the original disease and the syrinx. Syringomyelic symptoms were dominant in three cases of which the syrinx extended from the conus to the cervical cord. Initial symptoms of two cases with post-traumatic syringomyelia were tingling pains which began near the site of injury and extended rostrally. Metrizamide myelography revealed complete or incomplete block at the location of the tumors or the injuries. Delayed CT demonstrated the syrinx in all cases. The syrinx was always present near the sites of primary lesions. The communication between the syrinx and the fourth ventricle was suspected in three cases, and the communication of the syrinx and the spinal subarachnoid space was suspected in two cases. All cases underwent the surgical treatments. Total removal of the tumors were completed in two cases and relieved the majority of symptoms. On the other hand, a case with a thoracic astrocytoma underwent biopsy of the tumor and irradiation, followed by poor outcome. Syringo-peritoneal shunts were performed in two cases with post-traumatic syringomyelia and relieved pain, but neurological signs were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute-onset nontraumatic paraplegia in childhood: fibrocartilaginous embolism or acute myelitis?

Fibrocartilaginous embolus causing acute spinal cord infarction is a rare cause of acute-onset paraplegia or quadriplegia. Few cases of survivors have been reported in the neurosurgical literature, with most reports involving post-mortem or biopsy findings. There is little information on MRI findings in such patients. We present the youngest patient ever reported, and discuss the important differences between fibrocartilaginous embolus and acute myelitis of childhood. A 6-year-old girl with a history of back pain presented with sudden-onset nontraumatic paraplegia, with a clinical anterior spinal artery syndrome. Initial MRI scan revealed intervertebral disc disease at L1–2 and an incidental thoracic syrinx, but no cause for her acute-onset paraplegia was identified. Cerebrospinal fluid and other investigations were all negative. Sequential MRI scans revealed development of spinal cord expansion from T10 to the conus medullaris, with increased cord signal in the anterior aspect of the spinal cord. The intervertebral disc disease was unchanged. The imaging and clinical findings were caused by fibrocartilaginous embolus, which meant there was no need for spinal cord biopsy. The report describes the clinical and imaging criteria for diagnosis of fibrocartilaginous embolus, highlighting the case for avoiding an unnecessary biopsy. The clinical pattern in the paediatric group is discussed, with features differentiating it from acute myelitis of childhood. Received: 4 January 2000     

25例脊髓空洞症的临床特征与诊断

目的 :分析脊髓空洞症的临床特点以及 MRI对脊髓空洞症的诊断价值。方法 :回顾分析了 2 5例脊髓空洞症患者的临床表现 ,检查与诊断。结果 :脊髓空洞症是多种致病因素所致的综合征 ,以合并枕骨大孔区先天性畸形最为常见。其临床表现多样。节段性分离性感觉障碍并不是诊断脊髓空洞症的必要条件。 MRI在脊髓空洞症的确诊以及相应的病因学揭示中具有无可比拟的优越性。 MRI增强扫描有利于脊髓空洞症与髓内肿瘤的鉴别诊断。结论 :脊髓空洞症是多种致病因素所致的综合征。 MRI是最有价值的诊断方法 ,MRI增强扫描有利于其与髓内肿瘤的鉴别诊断。     

Idiopathic recurrent transverse myelitis with syringomyelia: a case report

Idiopathic transverse myelitis is a monophasic demyelinating disease of the central nervous system (CNS) and its recurrence is a rare entity. Existence of syringomyelia in the spinal cord in inflammatory CNS disease is not usually encountered. This case study describes a 45-year-old man who was admitted with features of a cervical demyelinating disease. The history of the patient indicated that this could be a recurring attack. Cervical MRI and laboratory examination of the patient showed evidence of recurrent transverse myelitis. The patient was managed with medical therapy. The follow-up cervical MRI of the patient 2 years later indicated syringomyelia in the cervical cord.     

A ferritin tracer study of compensatory spinal CSF outflow pathways in kaolin-induced hydrocephalus

Spinal drainage of cerebrospinal fluid (CSF) into the lymphatic system is important in physiological and pathological conditions in both humans and rodents. However, in hydrocephalus and syringomyelia the exact CSF pathway from the central canal into the lymphatic tissue around the spinal nerves remains obscure. We therefore induced syringomyelia and hydrocephalus in 36 Lewis rats by injection of 0.1 ml kaolin into the cisterna magna. At 2, 4 and 6 weeks later cationized ferritin was stereotactically infused into the cisterna magna of controls and into the lateral ventricles of hydrocephalic animals followed by dissection of brain, spinal cord and spinal nerves. CSF pathway and tracer flow were studied by light and electron microscopy. We found that in rats with kaolin-induced CSF outflow obstruction, CSF passes from central canal syringes through ruptured ependyma and dorsal columns into the spinal subarachnoid space, from where it is absorbed along spinal nerves into extradural lymphatic vessels. Taken into account that spinal hydrostatic pressure in humans differs significantly from pressure in animals due to the upright gait, we conclude that spinal compensatory CSF outflow pathways might be of even greater importance in human hydrocephalus.     

Progress in syringomyelia

Syringomyelia management is showing some progressive improvements following surgical methods of investigation and treatment. Investigation of simultaneous pressure changes in the cerebrospinal fluid pathways has illustrated the importance of craniospinal pressure dissociation in impacting the cerebellar and medullary tissues in the foramen magnum in hindbrain related syringomyelia. Such pressure differences may be referred to as 'suck' and similar changes are to be found in non-hindbrain related forms of syringomyelia such as those associated with spinal arachnoiditis. When cavities have formed then impulsive movements may occur with them and enlargement of the cavities may be continued by sloshing of the fluid within them. Investigations have been improved following the widespread use of water soluble contrast media and CT scanning with reconstructions after myelography.

A definite relationship between birth injury and hindbrain related syringomyelia has been established especially with cases showing arachnoiditis. The nature of the relationship to hindbrain hernia and basilar invagination remains unclear. Magnetic resonance imaging holds great promise particularly in showing hindbrain deformation in new-born babies, showing whether or not a communication commonly exists between the fourth ventricle and the cavities within the spinal cord in early childhood and also in outlining the changes in the spinal cord in the presence of acute traumatic paraplegia. Treatment still relies upon valved ventricular to extrathecal shunts for hydrocephalus, cranio-vertebral decompression to prevent suck and drainage of the syrinx in appropriate cases. Syrinx to extrathecal shunting may be preferred to shunts to the subarachnoid space. The peritoneum and the pleura are favoured sites and a valve is not necessary. The advances for the future may depend on earlier diagnosis and greater understanding of the mechanisms of pathogenesis in which MRI seems likely to play an increasingly important part.     

Late posttraumatic syringomyelic syndromes. Pathogenetic theories apropos of 3 cases

Three patients with a post-traumatic spinal cord cavity are described: clinical signs are identical to those of syringomyelia, but pain is more frequent. Diagnosis is made easier by magnetic resonance imaging (MRI) and a syringoperitoneal shunt is proposed for treatment. Nevertheless, if results are good, they seem worse than in idiopathic syringomyelia. The main pathogenic theories are discussed: the rupture and coalescence of microcysts developed at a distance of 1 or 2 mm from the transected spinal cord, subsequently leads to syrinx formation; haemorrhagic or ischemic post-traumatic areas could also lead to syrinx formation. Hydrodynamic factors could be expected and make the pathogenesis not far from syringomyelic one.     

Decompensated hydrocephalus causing syringomyelia and tetraparesis: a case report

Objective  Various causes for the development of syringomelia are discussed. The influence of hydrocephalus upon syringomyelia is rarely reported and its role remains unclear. Material and methods  We report a young female patient with shunt dysfunction and consequent syrinx development after child delivery. Results  The patient showed rapid clinical deterioration after delivery. Treatment was shunt revision and reconstitution of CSF flow in the posterior fossa. After surgery, the patient showed regressive syringomyelia going along with a quick and pronounced clinical improvement. Conclusion  Development of syringomyelia can be caused by CSF flow disorders and hydrocephalus and may be aggravated by increased intra-abdominal pressure.