Ifocus here on 4 important issues related

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1 GENERAL SCIENTIFIC SESSION 3 (HONORED GUEST LECTURE) Edward H. Oldfield, MD Department of Neurological Surgery, University of Virginia Health Science Center, Charlottesville, Virginia; Department of Medicine, University of Virginia, Charlottesville, Virginia This work is based on Honored Guest Presentation: Pathogenesis of Chiari I - Pathophysiology of Syringomyelia: Implications for Therapy, presented at the 2016 CNS Annual Meeting in San Diego, California. Correspondence: Edward H. Oldfield, MD, Department of Neurological Surgery, University of Virginia, PO Box , Charlottesville, VA eho4u@virginia.edu Received, January 17, Accepted, July 31, Copyright C 2017 by the Congress of Neurological Surgeons Pathogenesis of Chiari I Pathophysiology of Syringomyelia: Implications for Therapy: A Summary of 3 Decades of Clinical Research Ifocus here on 4 important issues related to the Chiari I malformation and syringomyelia. By what mechanism does a Chiari I malformation produce syringomyelia? What is the pathogenesis of the Chiari I malformation? Are the mechanisms underlying development of a Chiari I malformation and syringomyelia similar? How, exactly, is the pathophysiology related to the goals of surgery? The studies of my colleagues and myself are essentially the only studies of physiology in which direct measurements have been made in patients in the modern era of medicine. Thus, I summarize and integrate much, but not all, the work that my colleagues and I have done in this area at the National Institutes of Health (NIH) and the University of Virginia over the past 30 yr. Why might we want to know the answer to these questions? For esthetic reasons for one. As he stated in the early 1900s, William Osler held that our ambitions as physicians are To wrest from nature the secrets which have perplexed philosophers in all ages, to track to their source the causes of disease. 1 We also need to address these questions for practical reasons. Since the goals of treatment depend on disease mechanism, doing so would permit us to progress from empiric to logical treatment approaches, and allow us to select the most effective, while the least invasive, treatment. Moreover, there are many causes of syringomyelia at the foramen magnum and below (Table 1). Are we to expect different mechanisms of the origin and progression of syringomyelia for each? That seems most unlikely. ABBREVIATIONS: EKG, electrocardiogram; IOUS, intraoperative ultrasound; NIH, National Institutes of Health; PFD, posterior fossa decompression; PFDD, posterior fossa decompression and duraplasty; SAS, subarachnoid space Supplemental digital content is available for this article at There are, in general, 2 separate components to the clinical syndrome associated with the Chiari I malformation (Figure 1). Tonsil ectopia can exert external pressure of the cerebellar tonsils on the dura, brainstem, and spinal cord resulting in occipital pain, which may be exacerbated by coughing, sneezing, laughing, or straining. The pressure can also underlie weakness, spasticity, difficulty swallowing, and loss of proprioception. Surgical treatment almost always reverses these symptoms. On the other hand, expansion of a syrinx, which may cause pain, suspended sensory loss, weakness of the extremities, and loss of proprioception, can injure the spinal cord and produce damage that may or may not be reversed with successful treatment of the Chiari I and syringomyelia, residual damage that may underlie failure of the symptoms and signs to disappear after collapse of the syrinx. What is the best therapy? The optimal treatment is the least surgery that is safe and that eliminates the mechanism underlying the symptoms and progression. And that begs the question of what mechanism underlies the pathogenesis of the Chiari I malformation and of development and progression of syringomyelia. PRIOR THEORIES ON THE PATHOGENESIS OF SYRINGOMYELIA ASSOCIATED WITH THE CHIARI I MALFORMATION Until the mid-1990s, there were 3 generally recognized theories. Dr James Gardner first proposed his water-hammer theory in the 1950s, 2 which states that partial obstruction of the outflow of CSF [cerebrospinal fluid] from the fourth ventricle directs the systolic pulsations of CSF from the fourth ventricle through a patent central canal and transmits a systolic water-hammer pressure wave into the syrinx causing development and progression of syringomyelia. 3 The second theory 66 VOLUME 64 NUMBER 1 SEPTEMBER

2 PATHOGENESIS CHIARI I, SYRINGOMYELIA TABLE 1. Causes of Syringomyelia Congenital Chiari I malformation Chiari II malformation with myelomeningocele Dandy Walker malformation Acquired Cranial Any intracranial mass effect with tonsil herniation Hydrocephalous Intracranial tumor Pseudotumor cerebri Chronic subdural hematoma Others Foramen magnum Basilar impression Basal arachnoiditis (tuberculosis, etc) Tumors Lumbar CSF shunt with tonsil herniation Spinal Occluded subarachnoid space (arachnoiditis after trauma, meningitis, etc) Intramedullary and extramedullary tumors FIGURE 1. Midsagittal T2-weighted MRI of a young man who has slurred speech difficulty swallowing caused by compression of his lower brainstem and upper cervical segment of the spinal cord by a Chiari I malformation associated with syringomyelia. was the cranial-spinal pressure dissociation theory proposed by Bernard Williams, who proposed that a block to downward, but not upward, flow of CSF in the subarachnoid space (SAS) prolongs elevation of intracranial pressure over spinal intrathecal pressure and forces fluid from the fourth ventricle down a patent central canal and into the syrinx, producing communicating syringomyelia. 4 Thus, this proposed mechanism is based on abnormal venous pressures during Valsalva, coughing, lifting, and straining. Both theories require patency of the central canal between the base of the obex, into the spinal cord, and into the upper pole of the syrinx. However, all studies in the MRI era have shown only rare patients with a detectable channel between the fourth ventricle and the syrinx. In the third theory was Ball and Dayan suggested that the tonsils obstruct the rapid rostral movement of CSF from the spinal SAS to the cranial SAS during episodic increases in thoracic venous pressure causing sporadic increased spinal CSF pressure (during coughing, sneezing, and straining), which drives the CSF through the spinal cord surface and along extracellular paths to initiate and advance syringomyelia. 5 However, there are no compelling physiological studies to refute or confirm any of these 3 proposals. INITIAL CLINICAL AND PHYSIOLOGY STUDY AND ITS IMPLICATIONS In the late 1980s, my colleagues and I began to study the pathophysiology of Chiari I and syringomyelia at the NIH. I had spent the 1975 to 1976 academic year, the year before I began neurosurgical residency at Vanderbilt University, The National Hospital for Nervous Disease, Queen Square, London, much of the time working with Professor Valentine Logue, who had a special interest in syringomyelia. Logue had shown that opening the dura without opening the arachnoid was effective. 6 At the NIH, we used a surgical approach in which we opened the dura without opening the arachnoid, so that our measurements during surgery would not be compromised by changes in the physiology produced by loss of CSF. The critical step in that first study was caught on the video of ultrasound during surgery of a young man with a syrinx that extended from the thoracic segments to the very upper cervical portion of the spinal cord, permitting us to monitor it with the ultrasound during craniospinal surgery (see Video, Supplemental Digital Content 1). 3 There was prominent pulsatile movement of the walls of the syrinx with each heartbeat. Thus, it initially appeared that Gardner was correct, and we prepared and presented an abstract the annual meeting of the American Association of Neurological Surgeons emphasizing that. Later, when I was giving our weekly conference at the NIH and using this video, it became apparent that the video was showing systolic compression, not expansion, of the upper portion of the syrinx with each heartbeat. As we examine it, it becomes obvious that the upper portion of the syrinx is being compressed, not expanded, during the exaggerated downward movement of the tonsils during systole. Furthermore, there is no expansion of the syrinx during forced inspiration until after the dura is opened, the therapeutic step that produced complete resolution of the Chiari I malformation and syringomyelia in this young man. These observations are incompatible with the theories of Gardner, Williams, and Ball and Dayan. CLINICAL NEUROSURGERY VOLUME 64 NUMBER 1 SEPTEMBER

3 OLDFIELD In that initial study, anatomic MRI and phase-contrast MRI showed obstruction of the SAS at the level of the foramen magnum with no visible CSF space behind the cerebellar tonsils and no visible communication of CSF between the fourth ventricle and the central canal of the cord. Phase-contrast MRI demonstrated systolic downward movement of the syrinx fluid. These observations with anatomic and cine MRI are also incompatible with the theories of Gardner and Williams. Studies performed during the era of ventriculography led to important observations on the movement of ventricular and subarachnoid CSF during the cardiac cycle in normal persons. In the 1960s and 1970s, George du Boulay at The National Hospital for Nervous Disease studied the movement of CSF during the cardiac cycle during ventriculography in patients who proved to have normal studies. He showed that when a systolic bolus of blood is delivered to the brain, the third ventricle is rapidly squeezed by the rapid expansion of the cerebral hemispheres. 7,8 This produces systolic downward movement of CSF in the spinal SAS. He demonstrated that most of the CSF moving in and out of head during the cardiac cycle is from the basal cisterns (cisterna magna), not from the fourth ventricle, and showed that the cerebellar tonsils are relatively immobile during the cardiac cycle in normal persons, but descend and plug the foramen magnum by their downward movement with each systole in patients with Chiari I malformation. The predominant buffer to prevent abrupt increases in the intracranial pressure during the delivery of a systolic bolus of blood to the brain is the cerebral venous system, but there is normally also about 0.75 ml of CSF that rapidly moves from the basal cisterns of the posterior fossa and into the rostral spinal SAS. 7,8 Our observations during our initial clinical study suggested a previously unrecognized mechanism for progression of syringomyelia associated with occlusion of the SAS at the foramen magnum (Figure 2). 3 Thus, successful treatment requires only that we eliminate that block to the rapid movement of CSF in the SAS at the foramen magnum. The study indicated that the mechanism of the development and progression of syringomyelia is on the outside, not the inside, of the spinal cord. It also was apparent that the same mechanism may underlie other types of syringomyelia for instance, post-traumatic primary spinal syringomyelia, syringomyelia associated with a block of the spinal SAS by an arachnoid cyst, arachnoid web, etc. Thus, we had a hypothesis that we examined with a series of later studies. PROSPECTIVE STUDY OF THE PATHOPHYSIOLOGY ASSOCIATED WITH CHIARI I AND SYRINGOMYELIA We then investigated that hypothesis with a prospective study of the physiology of patients with Chiari I and syringomyelia, a study that was masterfully lead by my colleague, Dr John Heiss. 9 For this we examined several aspects of the craniospinal anatomy and physiology during the cardiac cycle (Table 2). We studied 20 patients with syringomyelia and Chiari I malformation before, during, and after surgery, and 18 normal subjects All pressure measurements were collected digitally, q30 ms. Pressure measurements, cine MRI, and intraoperative ultrasound (IOUS) were linked in time with the electrocardiogram (EKG). All patients received surgical decompression of tonsils and cisterna magna to produce free flow of CSF between the cranial and spinal SAS during the cardiac cycle. We assessed obstruction of CSF flow at the foramen magnum with 3 approaches (Table 2). In the Queckenstedt test, a lumbar puncture is performed and the jugular veins are compressed in a controlled fashion while measuring the rate of rise of pressure in the lumbar CSF. A block of CSF flow slows the rate of rise in lumbar pressure (Figure 3). There was no dorsal CSF space posteriorly at the foramen magnum in the patients, but after the surgery that space was greater than in the 18 normal subjects. For the group, there was a significant difference between the values before surgery in patients and normals, and between the values before and after surgery. There was elevated absolute pressure and pulse pressure in the cervical subarachnoid CSF space compared to the normal persons (Figure 4A). These returned to normal after surgery. The same was so for absolute CSF pressures in the lumbar region. Is the spinal CSF partially entrapped? This was examined by measuring for an obstruction to free flow of CSF between the head and lumbar CSF using Queckensted testing (Figure 4B) and for compliance (Figure 4C), by measuring the lumbar pressure before and after removing 10 ml of CSF and determining the pressure change per ml of CSF removed. As we had hypothesized, there was a block of the pressure to reach the lumbar CSF and the compliance was compromised before surgery both returned to normal after surgery. Is the upper portion of syrinx compressed by downward movement of tonsils during systole? For this, the IOUS was linked to the EKG while recording pressures from ventricular, cervical and lumbar CSF, and syrinx. It demonstrated compression of the upper portion of the syrinx during systole (Figure 4D; Video, Supplemental Digital Content 2). Using cine MRI, we assessed CSF movement in the syrinx and in the SAS at the foramen magnum before and after surgery. That demonstrated systolic downward movement of the syrinx fluid, but no evidence of CSF flow in the dorsal SAS at the level of the foramen magnum. We then used the same techniques to examine the pathophysiology of syringomyelia refractory to prior surgery in 16 patients with Chiari I and syringomyelia and found that the findings with MRI, cine MRI, IOUS, and the pressure measurements were similar to the pathophysiology established in Chiari I patients without prior surgery. 10 This argues that the next step of treatment considered in patients with failed prior surgery should be surgical decompression of the SAS at the level of the foramen magnum, unless there are factors that suggest that approach is unlikely to succeed, such as extensive arachnoiditis, etc. 68 VOLUME 64 NUMBER 1 SEPTEMBER

4 PATHOGENESIS CHIARI I, SYRINGOMYELIA PATHOPHYSIOLOGY OF PRIMARY SPINAL SYRINGOMYELIA Since the underlying basis of syringomyelia associated with the Chiari I malformation is obstruction of the SAS at the level of the foramen magnum, and primary spinal syringomyelia is associated with block of the SAS, but at a lower spinal level, we hypothesized that primary spinal syringomyelia is caused by an identical mechanism.11 We prospectively studied 36 adult patients with CLINICAL NEUROSURGERY spinal lesions obstructing the spinal SAS using the same set of techniques that we had used in the previous studies. In syringomyelia patients compared with healthy volunteers, cervical subarachnoid pulse pressure was increased pressure transmission to the lumbar CSF below the block was reduced, and spinal CSF compliance was decreased. Intraoperative ultrasonography showed that with each heartbeat systolic pressure waves compressed the outer surface of the spinal cord [in the area] superior to obstruction of the subarachnoid space. 10 VOLUME 64 NUMBER 1 SEPTEMBER FIGURE 2. Schematic drawings of the foramen magnum region. Sagittal view, illustrating the proposed mechanism of origin and progression of syringomyelia associated with Chiari I malformation of the cerebellar tonsils. A, In normal subjects during systole (right), as the brain expands with the reception of blood, CSF moves from the fourth ventricle into the cisterna magna; a larger volume of fluid passes from the basal cisterns to the subarachnoid space of the upper portion of the spinal canal. The magnitude of the systolic pressure wave that is conveyed to the CSF in the spinal canal dissipates with increasing distance inferiorly. During diastole (left), CSF flows rostrally across the foramen magnum. B, With obstruction to the rapid to-and-fro movement of CSF in the SAS across the foramen magnum (ventrally by anterior displacement of the brain stem and posteriorly by the impacted cerebellar tonsils) during systole (center) and diastole (left), brain expansion during systole is accommodated by abrupt caudal movement of the tonsils. The piston-like effect of this movement on the partially isolated spinal subarachnoid space imparts an accentuated systolic pressure wave to the spinal subarachnoid CSF. This acts on the surface of the upper segments of the spinal cord, abruptly constricting the syrinx, propelling the fluid in it inferiorly, and increasing bulk movement of CSF into the cord. C, With surgical decompression of the foramen magnum and tonsils, occlusion of pulsatile CSF flow across the foramen magnum is eliminated, normal physiology is restored, and syringomyelia disappears. Reprinted with permission from Oldfield et al.3

5 OLDFIELD TABLE 2. Components of Prospective Study of the Pathophysiology of Syringomyelia Associated With Chiari I Malformation A. Obstruction of CSF flow at foramen magnum? 1. Anatomic MRI 2. Cine MRI 3. Queckenstedt testing a. Normal subjects b. Patients 1) Before surgery 2) While measuring ventricular and lumbar CSF pressures at surgery 3) Three months after surgery B. Downward movement of tonsils on entrapped spinal CSF associated with increased pulse pressure in spinal CSF? 1. Excess spinal subarachnoid CSF pressure and/or pressure waves? a. Cervical and lumbar CSF and syrinx pressure measurements preoperatively and 3 mo after surgery b. Cervical and lumbar CSF pressure measurements in normal subjects 2. Entrapped spinal CSF? a. Spinal CSF compliance measured in patients before and after surgery and in normal subjects 3. Tonsils down during systole? Upper portion of syrinx compressed during systole? Simultaneous with tonsillar descent? a. IOUS linked to EKG while pressure recorded from ventricular, cervical CSF and lumbar CSF, and syrinx pressures 4. Flow of CSF and syrinx fluid and movement of brainstem, tonsils, and cord during cardiac cycle? a. Cine MRI before and 3 mo after surgery The findings are consistent with [our proposal] that a spinal subarachnoid block increases spinal subarachnoid pulse pressure above the block of the spinal SAS, producing a pressure differential across the obstructed segment of the SAS, and underlies syrinx formation and progression, and are similar to the results of [our] previous studies that examined the pathophysiology of syringomyelia associated with the Chiari I malformation. 10 This indicated that a common pathophysiology is associated with syrinx formation in patients with Chiari I malformation and primary spinal syringomyelia. ORIGIN OF THE CYST FLUID IN SYRINGOMYELIA ASSOCIATED WITH CHIARI I MALFORMATION AND PRIMARY SPINAL SYRINGOMYELIA With syringomyelia, the perivascular spaces of the cord are greatly dilated, they communicate with the syrinx, and reach the pial surface. 4 The[se] perivascular and interstitial spaces appear to be the route by which fluorescein, labeled albumin, horseradish peroxidase, and water-soluble contrast medium enters the extracellular space of the spinal cord and the syrinx 15,16 shortly after intrathecal injection. 6 This is consistent with Ball and Dayan s proposal that CSF enters the cord through these dilated spaces to produce syringomyelia by multiple microscopic connections with the subarachnoid space However, the results of our studies indicate that it [syringomyelia] is caused by abnormally high systolic pressure waves in the spinal CSF. 6,9-11 In the normal physiological setting, bulk flow of CSF into the perivascular spaces in the spinal cord, brain, and brainstem depends on the presence of pulsatile pressure, not sporadically increased venous pressure. 17 The observation by Brierley that more India ink moves into the dorsal aspect of the cervical segments of the spinal cord than into the lower segments after intrathecal injection suggests that bulk flow of CSF into the cord is also related to the presence of pulsatile pressure waves. The predominant involvement of the cervical segments of the spinal cord with Chiari I malformation is likely linked to the fact that the maximum pulsatile pressure waves in the spinal subarachnoid space occur in the upper portion of the cervical canal and are dissipated with increasing distances down the canal. 3,7,12,18 Later studies demonstrated that horseradish peroxidase penetrated to the central canal of the spinal cord of sheep after intrathecal injection, but this did not occur after dampening the arterial pulsations by partially ligating the brachiocephalic trunk. 19 Thus, small and large molecules move into the spinal cord from without by the combined forces of diffusion and bulk flow facilitated by pulse pressure in the CSF. The result of our studies, combined, indicate that the exaggerated absolute pressure and pulse pressure in the SAS in patients with syringomyelia associated with a Chiari malformation or primary spinal syringomyelia is an important component of the development and progression of syringomyelia. Thus, the results of all our studies were consistent with our original hypothesis. We should keep in mind that patients with increased intracranial pressure, increased intracranial pressure waves, and reduced CSF compliance from tumors, hydrocephalous, etc do not have syringomyelia unless there is tonsil herniation. The development of a syrinx requires increased absolute pressure and pulse pressure in the spinal CSF and at least a partial obstruction of the SAS with a partially isolated spinal CSF compartment. This explains the occasional presence of syringomyelia in patients with no Chiari malformation, but with obstruction of the SAS at the foramen magnum, initially described by Dr Oakes and his colleagues as the Chiari 0 malformation. 20 The same mechanism should apply to other entities, congenital and acquired, at the foramen magnum and below, that obstruct the spinal SAS and produce partial entrapment of the SAS below the level of involvement, including entities such as foramen magnum meningiomas, supratentorial and posterior fossa tumors, chronic subdural hematomas, etc that produce tonsil herniation, spinal arachnoid cysts, etc, associated with syringomyelia (Table 1). 70 VOLUME 64 NUMBER 1 SEPTEMBER

6 PATHOGENESIS CHIARI I, SYRINGOMYELIA FIGURE 3. Queckenstedt test. Pressure recordings show partial occlusion of CSF flow. The rate of rise in intrathecal pressure is shown in a healthy volunteer (left panel) and in a patient with Chiari I malformation and syringomyelia (right panels) before surgery and before the craniocervical junction is decompressed during surgery. After surgery, the rise in intrathecal pressure becomes normal. icp = intracranial pressure; lum = lumbar; s = seconds. Reprinted with permission from Heiss et al. 9 PATHOGENESIS OF CHIARI I MALFORMATION What is the pathogenesis of the Chiari I malformation? Several studies over the past 40 yr have demonstrated that the posterior fossa is too small for the tissue volume within it in many, but not all, patients with a Chiari I malformation. In the initial study in 1978, Nyland and Krogness demonstrated the small relative size of the posterior fossa in patients with Chiari I malformation. 21 Later, using CT scanning Dr Batzdorf and his colleagues demonstrated that, compared to normal persons, the ratio of the posterior fossa volume compared to the supratentorial volume was diminished in many, but not all, patients with a Chiari I malformation. 22 The same is so in other species. King Charles Cavalier spaniels, an offshoot of the King Charles spaniel, were bred in the 1500s to have a certain shape to the back of the head. That breeding also diminished the volume of the posterior fossa and lead many of them to have Chiari I malformation and syringomyelia. 23 But since only half the patients with Chiari I malformation in the Batzdorf study had a posterior fossa size below the normal range, there must also be mechanisms by which impaction of the tonsils in the foramen magnum and a Chiari deformity is produced other than a small posterior fossa. A few years ago it became apparent that although many patients have too much tissue for the posterior fossa space, producing a very crowed posterior fossa on MRI, others have MRI-visible extra space in the posterior fossa. We recently studied this and showed that among patients with Chiari I there are 2 distinct groups, crowded and spacious groups, with tonsil impaction in both sets of patients (Figure 5). 24 But when the tissue volume is related to the posterior fossa volume in individual patients, significantly more of the volume of the posterior fossa is occupied by CLINICAL NEUROSURGERY VOLUME 64 NUMBER 1 SEPTEMBER

7 OLDFIELD FIGURE 4. Summary of the results of a prospective clinical study of the pathophysiology of syringomyelia with Chiari I malformation. A, The absolute pressures and pulse pressures in the cervical and lumbar CSF are higher in patients than in 18 healthy volunteers before surgery and return to normal levels after surgery. B, Scatterplots in which the rates of rise in intrathecal pressure during Queckensted testing in patients with both Chiari I malformation and syringomyelia with those of healthy volunteers are compared. After surgery, the rise in intrathecal pressure becomes normal. C, Scatterplot showing that craniospinal compliance was compromised beforesurgery and returned tonormalaftersurgery. Compliancewas measured bydividing theamountofcsfremoved (10 ml) bythereduction in intrathecal pressure (in millimeters of mercury) that results. D, Graphs showing the syrinx diameter at C-2 by using cardiac-gated IOUS simultaneously with pressure recordings within the syrinx and cervical SAS. The syrinx contracts during cardiac systole when cervical subarachnoid pressure reaches its peak. Reprinted with permission from Heiss et al. 9 hindbrain tissue in the subset that appears to have a crowded posterior fossa. Earlier age at surgery and syringomyelia were more common in patients with the crowded subtype. The presence of the spacious subtype, which included 25 of the 45 patients, suggests that crowdedness alone cannot explain the pathogenesis of Chiari I malformation in many patients. Thus, in these patients there must be some other mechanism, currently unrecognized, that results in impaction of the tonsils in the foramen magnum. Another issue is whether a Chiari I malformation really is a congenital malformation of the cerebellar tonsils, as has long been thought. For instance, the patient shown in Figure 6 has a Chiari I malformation of the cerebellar tonsils. But it is acquired from the mass effect of a large meningioma it is not congenital. In 72 VOLUME 64 NUMBER 1 SEPTEMBER

8 PATHOGENESIS CHIARI I, SYRINGOMYELIA FIGURE 5. Distinction on MRI between spacious and crowded types of patients with Chiari I malformation. Note the clear differences in the absence or presence of SAS unoccupied by tissue in the posterior fossa of crowded and spacious subtypes of Chiari I malformation in these 2 patients. Midline sagittal MR images of illustrative patient with the crowded (left) and spacious (right) subtypes of Chiari I malformation. The arrows point to the limited and prominent CSF space above the cerebellar vermis in the crowded and spacious type, respectively. Reprinted with permission from Taylor et al, published online September 2, FIGURE 6. Midsagittal T2-weighted MRI (left) and coronal contrast enhanced MRI (right) in a patient with herniation of the cerebellar tonsils A caused by a large tentorial meningioma B. The abnormal anatomy of the cerebellar tonsils is identical to the anatomy of patients considered to have a Chiari I malformation. a prospective clinical study of 48 patients with a typical Chiari I malformation, most of whom had syringomyelia, we used MRI to serially examine the morphology of the hindbrain after decompressive surgery. 25 After surgery, the abnormal shape of the tonsils, the Chiari I malformation, consistently reverted to normal within a few months of surgery (Figure 7). By 3 to 6 mo after surgery, the peg-shaped tonsils became round, the cervicomedullary protuberance disappeared, and tonsillar ectopia diminished by 51%. This happens in essentially all patients with a Chiari I malformation after successful surgery to simply open the SAS to provide normal pulsatile CSF flow across the foramen magnum. If the Chiari I malformation is a congenital malformation, why do the cerebellar tonsils revert to normal after the impaction of the tonsils is relieved? The Chiari malformation is a result of systolic impaction of the tonsils in the foramen magnum with each pulse, which occurs over times per day with a pulse of 85. It is not a malformation, as it is acquired, not congenital. CLINICAL NEUROSURGERY VOLUME 64 NUMBER 1 SEPTEMBER

9 OLDFIELD FIGURE 7. Sagittal T1-weighted MRI before (left) and 1 yr after craniovertebral decompression with autologous pericranial graft (right). Surgical relief of the obstruction of the SAS at the foramen magnum resulted in disappearance of the abnormal appearance of the cerebellar tonsils, disappearance of syringomyelia, and elimination of the prominent dorsal hump at the cervicomedullary junction. This occurs in essentially all patients after successful surgery. WHAT S THE BEST INITIAL SURGICAL PROCEDURE FOR CHIARI I MALFORMATION WITH OR WITHOUT SYRINGOMYELIA Surgery is the only treatment for Chiari I malformation. The goal is to reverse symptoms associated with impaction of the cerebellar tonsils (headache, swallowing difficulty, etc), to arrest progressive myelopathy and prevent further loss of neurologic function in patients with compressive myelopathy at the foramen magnum, and to eliminate the mechanism underlying syringomyelia. 26 Certain general principles guide the selection of optimal therapy from among several surgical choices If it has equal or superior effectiveness, therapy associated with lesser risk should be selected in preference to treatment options associated with greater risk. 26 Thus, less invasive surgery is preferable to options of equal effectiveness but with more invasion of the central nervous system, such as coagulation or excision of the cerebellar tonsils or routine subarachnoid exploration of the outlet of the fourth ventricle. Combining simple craniocervical decompression and duraplasty, with or without opening the arachnoid, is successful in almost all patients. 27 Development of a strategy of surgery, then, might ask how much additional space is required at the level of the foramen magnum for successful reversal of the pathophysiology? Certain observations suggest that the additional space required is very small. For instance, Chiari I malformations in young children occasionally reverse without treatment as the skull grows faster than the brain in early childhood. 28,29 There are also indications that reversal of an extremely small increase in thickness of the soft tissues at the level of the foramen magnum associated with acromegaly is sufficient for a Chiari I malformation and syringomyelia to reverse after elimination of the excess growth hormone. 30,31 [T]he extra room required at the foramen magnum for successful surgery may be a fraction of a millimeter. 28 That any procedure that eliminates the obstruction of free, pulsatile movement of CSF in the SAS is successful explains why so many different procedures are effective, as all of them work because they usually eliminate that block. In recent years, surgical approaches have been introduced in which either bone decompression alone (without a dural incision) or bone decompression combined with a partial thickness dural incision is performed. These procedures have been successful in 80% to 90% of children (almost all reports are for pediatric patients) but are not effective in 10% to 20%, who require additional surgery in which the dura is opened (Table 3). 32 The advantages of using either bony decompression alone (without a dural incision) or bony decompression combined with a partial thickness dural incision as the initial procedure of choice are that both reduce the risk of complications associated with opening the dura and arachnoid, are usually successful, the patient has a more comfortable postoperative course, and it saves health care costs. 28,33 Despite these advantages, note that in patients with syringomyelia, the subset of patients with the most objective measure of successful surgery, PFD alone had a much lower likelihood of resulting in a response of the syrinx (64% in adults, 56% in children) compared to patients who received PFDD 74 VOLUME 64 NUMBER 1 SEPTEMBER

10 PATHOGENESIS CHIARI I, SYRINGOMYELIA TABLE 3. Comparison of Outcomes after Posterior Fossa Decompression (PFD) and Posterior Fossa Decompression and Duraplasty (PFDD) in Patients With Chiari I Malformation Outcome PFDD (%) PFD (%) Adults a Clinical improvement 29/33 (88%) 37/45 (87%) Decreasein syrinx size 14/14 (100%) 21/33 (64%) Additional surgery 0/33 (0%) 1/11 (9%) Complications 14/33 (42%) 4/45 (9%) Pediatric b Clinical improvement 44/56 (79%) 51/79 (65%) Decrease in syrinx size 40/46 (87%) 9/16 (56%) Additional surgery 3/143 (2%) 15/119 (13%) Complications 28/135 (22%) 3/111 (3%) a Data by combining the results of the reports by Chauvet, Isu, Kotil, and Romero. 35,38-40 b From meta-analysis by Durham and Fjeld-Olenec. 32 (100% in adults, 87% in children) Almost no adults who received PFDD required additional surgery compared to 9% of the patients who were treated with PFD. 28 See Table 3. A meta-analysis comparing the outcomes of the 2 approaches in children demonstrated reduced need for reoperation, higher incidence of clinical improvement, and a higher likelihood of response of the syrinx in patients who received a dural graft. However, that came at the expense of a higher incidence of CSF leaks and pseudomeningoceles and a greater likelihood of infection. Thus, the arguments for using posterior fossa decompression (PFD) as the initial procedure are that it reduces the morbidity of the procedure and it is usually successful, and these features outweigh the disadvantages of knowing that further surgery to open the dura will be required in 10%-20% of patients treated in this fashion On the other hand, those favoring PFDD discuss the value of having the capacity to visually assess the subarachnoid space to examine for a subarachnoid abnormality (arachnoiditis, dural or arachnoid band, arachnoid cyst) after opening the dura, whether the arachnoid is left intact or not, and argue that the consistency of success with a single operation outweighs the disadvantages associated with the greater incidence of complications and [the need for] additional surgery later. 34 It also seems that the response of the syrinx and the return of the tonsils to a normal shape and position is delayed, on average, several months with PFD compared to posterior fossa decompression and duraplasty (PFDD). Ideally there would be a method of determining during surgery the least amount of surgery that each individual patient requires to open the subarachnoid space at the foramen magnum. That is, it would be valuable if it could be determined during surgery if removal of bone alone, removal of bone combined with a partial thickness opening of the dura, or bone removal and opening the dura, but not the arachnoid, is sufficient in individual patients, so that the surgery could stop at the least stage that is likely to be successful. Intraoperative ultrasound has been used for this purpose to examine the distance between the inner layer of dura and the posterior edge of the cerebellar tonsils and to assess the pulsatility of the cerebellar tonsils and the spinal cord surrounding a syrinx, and to see if bony decompression or partial thickness dural incision provided the extra space needed, 28 although its value has not been established. 3,35,36 Intraoperative MRI, which permits anatomical imaging and imaging of CSF and tissue movement, should also be valuable for determining during surgery if each step of surgery has provided 1) additional space between the posterior margin of the cerebellar tonsils and the inner layer of dura, and 2) sufficient space at the foramen magnum for normal pulsatile movement of CSF in the subarachnoid space at the level of the foramen magnum, by using phase-contrast MRI. 34 In a prospective clinical study, we used intraoperative anatomic and cine MRI to assess the subarachnoid contents at the level of the foramen magnum. 34 The results of intraoperative MRI during surgery, when the patient s neck was flexed for surgery, mislead us into concluding during surgery that bone removal alone had provided the additional space required, based on the space between the posterior margin of the tonsils and the dura and CSF flow behind the tonsils on cine MRI. So we stopped the procedure at that stage in 12 of the 18 patients. Eight of those 12 patients (67%), all adults, required either another operation later in which the dura was opened (3 patients) or had no (4 patients) or incomplete (1 patient) relief of their symptoms, to the extent that repeat surgery was recommended in several of them. Therefore, this small study suggested (1) that the use of intraoperative imaging for Chiari I malformation in general, whether by ultrasound or intraoperative MRI, is limited by the CSF flow dynamics across the foramen magnum changing significantly when the patient is positioned for surgery and (2) that posterior fossa decompression alone, with or without a partial thickness dural incision, is probably not a good choice for adults. Some investigators advocate a decompressive procedure that opens the arachnoid membrane, removes or shrinks the inferior portion of the cerebellar tonsils, and attempts to enlarge the CSF pathways beyond what is achievable with bony decompression and duraplasty alone. 26 The utility of these approaches appears to be similar to approaches that simply open the dura, with or without opening the arachnoid and placement of a dural graft, without subarachnoid exploration. In most patients, the goals of surgery are accomplished with either approach. However, excision or coagulation of the cerebellar tonsils can lead to arachnoiditis and subarachnoid scarring and initiate a process that is difficult to treat successfully. It is unnecessary. Rarely the patient fails to respond to decompressive surgery, as the pathophysiological mechanism has not been eliminated, because of inadequate bone removal or an extradural pseudocyst that prevents the SAS posterior to the cerebellar tonsils from expanding. 10 In these cases, a second operation usually is CLINICAL NEUROSURGERY VOLUME 64 NUMBER 1 SEPTEMBER

11 OLDFIELD FIGURE 8. On T1-weighted sagittal MR images, a syrinx that is present before surgery A is little changed by 1 wk after surgery B,butthenprogressively becomes smaller by3 moc and 1 yr D after surgery. Reprinted with permission from Wetjen et al. 35 successful by correcting conditions extradurally. Maintaining the arachnoid membrane during craniocervical decompression, with or without duraplasty, provides an additional biological barrier to intrathecal scar formation. If the arachnoid is opened, cerebrospinal leakage through the skin can also occur, but should not occur if the dural closure and the fascial closure are secure, except for cases in which increased intracranial pressure associated with pseudotumor cerebri, hydrocephalus, etc is present. Surgical failure can also result from intradural processes that go unrecognized at surgery, such as an arachnoid cyst obstructing the SAS or a web covering the outlet of the fourth ventricle, especially with PFD alone, during which the only view of the intradural anatomy is with IOUS. The results of surgical therapy can be evaluated noninvasively using clinical assessment and MRI. MRI scans of the cervical spine and posterior fossa are performed at 2 to 3 and 12 mo after surgery to evaluate if CSF pathways have been restored at the foramen magnum, and assess for reversal of the abnormal morphology of the cerebellar tonsils, or the presence of a pseudomeningocele, and to detect if an associated syrinx is becoming progressively smaller. Successful surgical treatment results in improvement or reversal of symptoms, disease stabilization, and in many patients, neurological improvement. In a prospective clinical study, we used MRI to monitor 29 consecutive patients with Chiari I malformation and syringomyelia (Figure 8). 37 The median time to syrinx narrowing was 3.6 months following surgical decompression After surgery 94% of patients had improved symptoms symptoms resolved incompletely in 68% Clinical improvement [generally] occurred before partial or complete disappearance of the syrinx on MR images. 37 Thus, most patients with syringomyelia improve after decompression for CM-I, but some have residual symptoms. A collapsed syrinx (absence of distention of the spinal cord) indicates that the pathophysiology has been reversed by treatment regardless of the completeness of elimination 37 of the syrinx on MRI. SUMMARY It is notable that all the observations in our several clinical studies have been consistent with the mechanism identified during the initial study. To summarize, in the preceding pages I emphasize 4 important issues related to the Chiari I malformation and syringomyelia. By what mechanism does a Chiari I malformation produce syringomyelia? The mechanism of the origin and progression syringomyelia is on the outside, not the inside, of the spinal cord. What is the pathogenesis of the Chiari I malformation? Are the mechanisms of development of a Chiari I malformation and syringomyelia similar? The Chiari I malformation, and other processes, such as posterior fossa tumors, bilateral chronic subdural hematoma, pseudotumor cerebri, that impact the tonsils in the foramen magnum and produce identical anatomic changes, are simply a result of impaction of the tonsils in the foramen magnum. It is an acquired, not a congenital, phenomenon. The Chiari I malformation and the origin and progression of syringomyelia are the same impaction of the cerebellar tonsils in the foramen magnum. How, exactly, is the mechanism related to the goals of surgery? Effective treatment occurs when the obstruction to free, pulsatile subarachnoid CSF flow at the foramen magnum is eliminated. Effective treatment occurs with any procedure that accomplishes this. Disclosure The author has no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. REFERENCES 1. Osler W. Chauvinism in Medicine: An Address Before the Canadian Medical Association, Montreal, September 17, Philadelphia, PA: Williams & Wilkins; Gardner WJ, Angel J. The mechanism of syringomyelia and its surgical correction. Clin Neurosurg. 1958;6: Oldfield EH, Muraszko K, Shawker TH, Patronas NJ. Pathophysiology of syringomyelia associated with Chiari I malformation of the cerebellar tonsils. Implications for diagnosis and treatment. J Neurosurg. 1994;80(1): VOLUME 64 NUMBER 1 SEPTEMBER

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