Research priorities for syringomyelia

Session II was devoted to discussions of CSF dynamics.

Gordon McComb spoke about the physiology of bulk CSF flow. He described two types of syrinx--communicating and noncommunicating, which are differentiated by the composition of the cavity fluid. The majority of CSF is produced by the choroid plexus, with the remaining portion originating from the parenchyma. A threefold turnover of CSF occurs daily, a very active process. The hydrostatic pressure differential between the newly formed CSF and the site of drainage in the ventricles and the parenchyma causes the CSF to circulate. Other factors contributing to CSF circulation include pulsations of the brain, arterial tree respiratory variations, changes in body position, and ciliary action. There is normally an ongoing process of communication between CSF in the subarachnoid space and fluid in the spinal cord parenchyma. In syringomyelia associated with hindbrain malformation, there is also a process of communication between the syrinx and the subarachnoid space. The therapeutic goal should be to alter this dynamic process to either prevent or collapse the syrinx.

Bernard Williams spoke about his research concerning pressures in the CSF and their relationship to syringomyelia. The presence of syringomyelia suggests a balance of forces such that at some time during the patient's activity in some part of the spinal cord, the pressure on the outside is higher than the pressure on the inside. Otherwise, the syrinx would collapse spontaneously. To validate this supposition, persons with and without cervicosyringomyelopathy and diseases of the spine were studied by simultaneously monitoring the lumbar CSF pressure, the ventricular pressure, and the venous pressure to determine how these pressures changed during coughing or Valsalva's maneuver. A differential trace (the lumbar trace minus the ventricular trace) was displayed. Fluid was observed to surge up the spine in response to any sudden increase in abdominal thoracic pressure. This might be described as a pressure-dependent ballistic impulse, or more tersely as ``slosh.''

The human neuraxis has a large rostral capacitance (the compressibility of the veins and the compressibility of the vascular bed), but only a small caudal capacitance. The caudal capacitance is affected by the external veins and by the elasticity of the dura. Valsalva's maneuver begins a fluid wave at the caudal end, which moves rostrally until it encounters a blockage. It may then rebound to produce an area of consternation, diffuse chaotic flow, which may be responsible for syrinx filling. Considering the pressurevolume fluid curve, reducing the volume of CSF will reduce the efficiency with which Valsalva's maneuver will expand the syrinx. This has been the rationale for the surgical placement of a valve to lower the CSF pressure.

Dieter R. Enzmann spoke on the use of MRI to study the gross physiology of CSF motion, CSF flow, and brain motion in Chiari I malformations. The quantitative cine mode MRI allows dynamic measurements of CSF movement in the cranium and spinal column. The MR technique utilizes a phase contrast cine MR pulse. Images are generated to provide 16 views during the cardiac cycle, at fairly high resolution, with relatively thin slices. Flow is measured in the subarachnoid space and in the syrinx. In addition, brainstem motion is measured from the midbrain to the medulla. Measurements may include the minimum, average, and maximum velocity of fluid movement at each point in the spinal column. Pre- and postoperative images of a syrinx can be generated in both the sagittal and axial planes.

Rocco A. Armonda spoke on the use of quantitative cine mode MRI to study patients with syringomyelia associated with the Chiari I malformation. Images were cardiac gated so events could be temporally related. The direction of flow, cranial or caudal, was determined during various phases of the cardiac cycle. Drawbacks were that pulsatile velocity, not flow or bulk flow, was measured, and that the CSF pulse pressure was not measured. In normal individuals, at C2 in early systole there is caudal CSF flow with rapid downward flow of CSF. When patients were treated by posterior fossa decompression and duraplasty, there was usually a decrease in the size of the syrinx, accompanied by an increased velocity in the foramen magnum and foramen of Magendie. Preoperatively, in early systole, there is predominantly cranial flow. Postoperatively, there is an increase not only in the magnitude but also in the duration of caudal CSF flow.

Edward H. Oldfield spoke of the pathophysiology of syringomyelia and the implications for diagnosis and treatment. There is no consensus on the pathophysiology of syringomyelia, particularly in Chiari I malformations. There is a great diversity in the surgical approaches that are currently being used. Detection of the pathophysiology preoperatively or during surgery may provide the basis for choosing the least invasive therapy. The use of MRI scans, pre- and postoperatively, allows for observation of the syrinx and dynamic changes that occur in the CSF and syrinx fluid during the cardiac cycle. Use of intraoperative ultrasound allows monitoring of the anatomy of the spinal cord, the syrinx, and the cerebellar tonsils during surgery. In patients with Chiari I malformation, there is an occlusion of the subarachnoid space at the foramen magnum. In one operative study, images were obtained before and after the dura was opened. Before the dura was opened, the tonsils moved abruptly downward and the cervical portion of the syrinx constricted with each systole. After the dura was opened, but with the arachnoid still intact, there was no longer pulsatile motion of the spinal cord, and downward movement of the tonsils ceased. Patients were treated only by decompression of the foramen magnum and dural grafting, without opening the arachnoid. All patients had resolution of syringomyelia within 3 to 6 months of surgery. The results of this study imply that the mechanism of syringomyelia is external to the cord and that the transmission of a pulsatile systolic pressure wave in the subarachnoid space underlies the development and progression of syringomyelia.

Session III was devoted to clinical management of syringomyelia.

Richard G. Ellenbogen discussed CSF dynamics and clinical outcome in a study of children and adults with Chiari I malformation, with and without syringomyelia. There is an obstruction of CSF flow around the craniocervical junction, with short periods of cranial CSF flow from the subarachnoid space, followed by sustained periods of caudal CSF flow. Shunting will collapse the syrinx but does not necessarily restore CSF flow. Decompression of the posterior fossa and foramen magnum will restore relatively good CSF flow, but normal levels are not obtained Failures may result because CSF flow is never as good as in the normal individual.

Albert L. Rhoton discussed his surgical treatment of syringomyelia associated with Chiari I malformation. The primary goal has been to decompress the Chiari I malformation with a suboccipital craniectomy and upper cervical laminectomy in combination with duraplasty. In those cases in which scarring occludes the outlet of the fourth ventricle, an opening is made in the scar to reestablish the outlet for the fourth ventricle. In those cases in which the dorsal root entry zone is paper thin as a result of a large syrinx, a dorsal root entry zone myelotomy is done by inserting a wick, not a shunt, into the syrinx. Two of 80 patients had an increased deficit as a result of the myelotomy: In one patient there was a very mild increase in sensory deficit of which he was unaware, but which was detectable on examination, and in another patient who had multiple prior operations to decompress the Chiari I malformation and drain the syrinx, there was a moderate increase in the deficit as a result of having to dissect through extensive scar. Advising the patient of the expected outcome before treatment is a critical part of management. Ideal treatment should arrest the progression of the deficits, including the size of the areas of numbness, and stabilize muscular strength.

Thomas H. Milhorat presented some clinical findings. One hundred fifteen patients with Chiari I malformations, hydrocephalus, basilar impression, intraspinal tumors, posttraumatic injury, and other types of problems were represented. Imaging studies showed that there were three types of cavities: central cavities, central cavities that expand into the paracentral tissues, and paracentral cavities. The clinical signs associated with the different cavity patterns differ. For central cavities, there were nonspecific, long tract signs, no cranial nerve deficits, and very few segmental findings except for pain-associated sensory loss. For paracentral cavities, including those that extended from the central cavities, there were specific segmental sensorimotor neuron deficits. Axial plane MRI provides the opportunity to make precise correlations with the symptoms and signs of the disorder.

David G. McLone discussed treatment of syringomyelia associated with Chiari II malformations. Chiari II is a congenital malformation associated with myelomeningocele, hydrocephalus, and often lower cranial nerve abnormalities. In addition to the hindbrain herniation seen in Chiari I, the posterior fossa in Chiari II is too small for the cerebellum, and there is upward herniation into the middle fossa. For these reasons, decompression of Chiari II does not always work. Deterioration in children with spinal bifida could be due to a shunt problem, a problem with a Chiari malformation, or a tethered cord. The most likely cause for deterioration in these children has been shunt malformation, resolving with correction of the shunt. Decompression of the posterior fossa does not work in a high percentage of patients, and may result in shunt malfunction and immediate herniation into the decompression. When the problem was tethered cord, untethering the cord restored some children to their previous state and stabilized them. In other children, both revising the shunt and untethering the cord were required.

Peter W. Carmel spoke about postoperative findings in Chiari I which were followed with MRI. The degree of tonsillar prolapse and the size of the syrinx were measured pre- and post-operatively. In many cases, post-operatively, the tonsil moves progressively back toward the posterior fossa and lost its pointed appearance, becoming more rounded. The treatment in these cases was decompress the posterior fossa, leave the dura open, leave the arachnoid open, and close just the muscle. A dural graft was not done. Along with resolution of the tonsillar prolapse, there was some resolution of the syrinx. Only a small number had total resolution of the syrinx. But there was a progressive decrease in syrinx size, which continued for well beyond 6 months after surgery, to at least 50% reduction at the end of one year.

Session IV covered the area of treatment of posttraumatic syringomyelia.

Ulrich Batzdorf discussed the treatment of syringomyelia after spinal cord injury. Cyst formation can develop after spinal cord injury with or without neurologic deficit. Cysts can be collapsed by shunting, but often complications result in reexpansion and the need for subsequent surgeries and reshunting. Furthermore, placing shunts in the spinal cord can add to the neurologic deficit. Shunts usually fail because of growth of glial tissue into the openings, and may result in further neurologic damage if removal becomes necessary. Patients who have multichambered cyst cavities are extremely difficult to treat with a single shunt. When shunting is difficult, the use of a decompressive treatment, such as a dural graft with a bypass for CSF, may be a more appropriate treatment. In cases where there is a spinal deformity, such as kyphosis, along with the syringomyelia, the deformity must be corrected to treat the patient successfully. Treatment of cysts with shunts should be considered a treatment of last resort. If shunts are to be used, the design is important. One type of shunt designed with multiple perforations allows collapse along the full length of the catheter, but may result in more extensive damage if removal becomes necessary.

Scott P. Falci spoke about progressive posttraumatic myelopathies, cystic and noncystic. Both have the same clinical manifestations. There is sensory loss, motor loss, increased spasticity, hyperhidrosis, pain, autonomic dysreflexia and/or Horner's syndrome. In noncystic or myelomalacic myelopathy, the most common problem is tethering of the spinal cord and rootlets to the dura. This results in tensile injury to the cord and rootlets from loss of normal spinal cord and rootlet motion and impairment of normal spinal fluid flow. The surgical indications are progressive sensory and motor loss and the late onset of central deafferentation pain. The surgical technique used involves a careful dissection to release all tethering of the cord and rootlets from the dura to the level of the dentate ligaments and neural foramina. The anterior subarachnoid space is entered to increase CSF flow, and expansion duraplasty is performed to minimize retethering. Somatosensory evoked potentials are used to monitor the technique and evoked potential improvement in latency can usually be obtained.

With cystic myelopathy, true cavitation of the spinal cord occurs, along with spinal cord and rootlet tethering. Small cysts may resolve with untethering and expansion duraplasty alone; however, larger cysts require a shunt. Cyst subarachnoid and cyst peritoneal shunts are employed.

Surgical treatment for both cystic and noncystic myelopathies prevents neurologic deterioration in the vast majority of cases. Recovery of lost sensory and motor function as well as the resolution of central deafferentation pain generally occurs if the onset of lost function and presentation of central pain is within 3 months of the time of surgical treatment. Only 40% to 50% of patients recover lost function and have resolution of central pain if treatment occurs 6 months after onset. It would be unusual, however, for a patient not to make some neurologic recovery after an untethering or cyst shunting procedure.

Barth A. Green spoke about surgical management of spinal cord cysts in cases of posttraumatic lesions. The focus of the talk was surgical techniques and protocols. MRI scanning was the preferred imaging tool, but in some cases, because of metal artifacts after spinal cord injury, enhanced CT scans were used. To prevent progressive damage to the spinal cord, it is better to treat the cysts prophylactically, before symptoms appear. Surgical treatment of cysts involved the use of subarachnoid shunts, in most cases, and expansive duraplasty. There was a 15% shunt failure rate, with two or more shunting procedures required. An effort to prevent tethering of the spinal cord after surgery requires keeping the patient off his or her back after surgery and mobilizing the patient as soon as feasible.

James L. Little presented the use of electrophysiologic tests to evaluate neurologic function in spinal cord-injured patients. Electrophysiologic studies provide information about upper motor neuron and lower motor neuron effects and can be useful as a monitor of the syrinxes. In some cases, the motor unit amplitude, from needle EMG studies, becomes abnormal long before the decline in actual strength. This suggests there is silent neurologic damage occurring in the presence of the syrinxes. Motor neurons are capable of reinnervation of muscle fibers and will therefore compensate for neuronal loss. Only when motor neuron loss is considerable are there signs of weakness. In other cases, changes in strength indicate possible syrinx problems. With weakness, there is a decrease in the size and firing rate of the motor units After decompression or shunting, there is an improvement in strength and in the size and firing rate of the motor units.

Central motor conduction measurements are abnormal and prolonged in posttraumatic syrinxes. Improvements in F waves and central motor conduction can be used to detect decompression of a syrinx. In cases where there is clinical improvement of symptoms, but not collapse of the syrinx, electrophysiologic monitoring can be used to show successful shunting when the MRI does not. Not all neurologic progression after spinal cord injury can be attributed to posttraumatic syringomyelia. There are also cases of inadequate decompression, late spinal instability, spinal stenosis, traumatic tethered cord, and peripheral nerve entrapment. Screening for a posttraumatic syrinx might include serial clinical examinations, MRIs, electrodiagnostic studies, and quantitative myometry Elecrodiagnostic methods for monitoring syringomyelia should include ways to look at upper motor neurons, such as with the central motor conduction time of the motor evoked potential and with motor unit firing rate during maximal effort, and ways to look at lower motor neurons, such as with F waves and motor unit counting.

Robert P. Yezierski spoke about his work on the development of experimental animal models for syringomyelia.These models will help identify some of the factors that contribute to the formation and expansion of cavities in the spinal cord. Release of excitatory amino acids is one example of neurochemical changes that occur after spinal cord injury. There are also changes in concentrations of certain neurotransmitters, fluxes in ion gradients, and toxic metabolic byproducts. Quisqualic acid, a non-N-methyl-D-aspartate agonist, injected into the spinal cord resulted in selective elimination of different populations of neurons depending on concentration, volume, and site of injection. After longer periods of time, cavities were formed in the spinal cord. These cavities were generally unilateral and varied in size and number. In some cases there was a slight dilatation of the central canal.

To study tethering resulting from inflammation or arachnoiditis, aluminum silicate or kaolin is injected into the spinal cord. This results in tethering, where adhesions form between the spinal cord and the dura. In addition, there is the formation of a large number of small cyst-like cavities in the white matter and damage to the gray matter, similar to what is seen in ischemic injury. It has been hypothesized that tethering of the spinal cord leads to a reduction in spinal cord blood flow, which triggers a mechanism that releases excitatory amino acids, which in turn causes tissue damage and leads to excitotoxic cascades, eventually leading to the formation of cavities within the spinal cord.

To mimic ischemic injury, inhibitors of nitric oxide synthase were injected into the spinal cord. This resulted in a reduction in blood flow, causing tissue damage similar to that seen with excitatory amino acids, and a breakdown of the blood-brain barrier. There was release of potentially toxic substances from the vasculature into the spinal cord. In addition, the excitotoxic mechanism was triggered by an increased release of excitatory amino acids. Both of these processes can lead to extensive tissue damage in the spinal cord.

Animal models of syringomyelia have permitted studies concentrating on pain and pain mechanisms. Certain behaviors are reflective of pain. These behaviors include allodynia, which is a heightened response to a non-noxious stimulus, and hyperalgesia, which is a heightened painful response to a noxious stimulus. An interesting observation in the animals with spinal cord lesions was that after a 2-week delay, there was an abnormal grooming behavior. This behavior may be due to the presence of paresthesia or dysesthesia in the periphery. The behavior progressed from scratching to severe grooming in a proximal to distal trajectory. The grooming typically began in the dermatome associated with the location of the cavitation within the spinal cord. Where the cavitation was unilateral, the grooming was observed only on one side; bilateral cavitation resulted in grooming on both sides. Electrophysiologic measurements indicated that there was abnormal neuropil The neurons were hyperexcitable and no longer gated their responses, and there were long postdischarges. Use of this model to study the pain response may be important for directing interventions to reverse the hyperexcitable state so that persistent pain can be diminished.