Accepted Manuscript Adult-Onset Syringomyelia - From theory to practice and beyond B Roy Chaudhary, MBBS, MSC, FRCS Michael G. Fehlings, MD, PhD, FRCSC, FACS PII:
S1878-8750(14)00754-2
DOI:
10.1016/j.wneu.2014.08.033
Reference:
WNEU 2524
To appear in:
World Neurosurgery
Received Date: 25 July 2014 Accepted Date: 15 August 2014
Please cite this article as: Chaudhary BR, Fehlings MG, Adult-Onset Syringomyelia - From theory to practice and beyond, World Neurosurgery (2014), doi: 10.1016/j.wneu.2014.08.033. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT PERSPECTIVES
Michael G. Fehlings, M.D. Toronto Western Hospital 399 Bathurst St. West Wing, 4-449 Toronto, ON Canada M5T 2S8 Ph. 416-603-5627 Email: [email protected]
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Adult-Onset Syringomyelia - From theory to practice and beyond
M AN U
SC
Syringomyelia is a rare neurological disorder estimated to affect 9 per 100,000 of the population [4] resulting from pathological cyst formation within the spinal cord. The classic presentation includes a dissociated and/or suspended progressive sensory loss in a cape like distribution with spasticity, lower limb hyperreflexia and neuropathic pain. However syringomyelia occurs in association with a spectrum of clinical conditions, variable spinal cord anatomical localization and diverse histopathological patterns. To reflect this it can be classified as [11] : 1) Communicating central canal syrinx 2)Non-Communicating central canal syrinx 3)Atrophic cavitations 4)Neoplastic cavitations.
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Amongst adult cases approximately 50% of syringomyelia is associated with Chiari 1 malformations whilst the of the remainder of cases are considered acquired with 25% being associated with spinal cord trauma (post traumatic syringomyelia) or arachnoiditis which are all non-communicating central canal syringes [4]. Spinal cord injury (SCI) is an important pathology with a significant socio-economic burden [18] and upto 51% of these patients are reported to develop spinal cord cysts [3]. Symptomatic progression due to such post-traumatic syringomyelia (PTS) occurs in a smaller subset of SCI patients and can present with back pain, ascending sensory loss, autonomic dysreflexia, spasticity and worsening motor deficits.
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Despite the first clinical and accompanying autopsy description of syringomyelia presenting as an abnormal cavity in the cervical spinal cord dating back to 1803 by Antoine Portal [14], a unifying pathophysiological basis for syringomyelia continues to be elusive. We have previously recapitulated the proposed theories [13] salient amongst which are those from Gardner [8], Williams [17] and Oldfield [12]. Many of the above reports explain the pathophysiology of the most common forms of syringomyelia i.e. those associated with Chiari malformations. In such cases surgical redress of the chiari malformation often provides clinical and radiological improvement [10]. However none of these proposed mechanisms explain all the variations in reported clinical cases and histopathological findings [5]. It is interesting to note that in some cases of syringomyelia with apparent absence of tonsillar decent typical of Chiari 1 malformations, contents of the posterior fossa are caudally compressed in the so called Chiari malformation Type 0 [6]. Even more remarkable is that such co-relation is borne out in other mammalian species such as the Cavalier King Charles Spaniel dog breed amongst which almost half the population over 4 years of age has syringomyelia [16].
ACCEPTED MANUSCRIPT
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In non-Chiari syringomyelia such as PTS, In-vivo animal models [15] demonstrate that the combination of SCI (by clip application) and subarachnoid kaolin injection to induce arachnoid scarring results in a significantly greater syrinx formation and perilesional myelomalacia than SCI alone. This supports the role of altered fluid dynamics and pathological subarachnoid CSF flow being propagated into the medullary tissues along the extracellular compartment subsequent to an initial ‘syrinx generating ictus’ such as secondary pathological mechanisms following spinal cord injury [7]. The PTS group also demonstrated greater parenchymal inflammation and scarring relative to the SCI alone as evidenced by significant increases in cytokine (IL-1α, IL-1β) and chemokine (MCP-1, GRO/KC and MIP-1α) production confirming the potentiation of parenchymal pathophysiology by arachnoiditis [1]. Of note is the reduction of post-traumatic parenchymal fibrous scar formation in these animal evidenced by reduced Chondritin Sulphate ProteoGlycan (CSPG) deposition and reduced IL-1α levels when a hydrogel of hyaluronan and methy cellulose (HAMC) was injected into the subarachnoid space 24hrs post PTS induced injury to reduce inflammation17. This provides for the basis for one of the possible options [7] for clinical intervention in patient who maybe at greater risk of developing PTS after SCI.
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In this issue, Ghobrial et al [9] present a detailed systematic review of the outcomes of arachnolysis or CSF diversion in syrinomyelia patients presenting to adult neurosurgical practice. To best inform clinical practise pertaining to the choice of arachnolysis or CSF diversion, they have excluded studies that prima facia deal with chiari related syringomyelia which form a significant proportion of syringomyelia patients. However due the heterogeneity and paucity of prospective studies on the topic the selection of review articles still result in 27 percent of patients having Chiari malformations as the authors acknowledge. An additional difficulty for surgical planning is the absence of pre-operative diagnostic imaging to confirm arachnoid adhesions with various reports detailing occult arachnoid lesions in syringomyelia patients which were demonstrated only surgically [5]. Thus the choice of intervention becomes ultimately an intra-operative decision. We therefore agree with the authors that these factors make it difficult to generalize these findings for recommendations for the treatment of non-Chiari related syringomyelia. We also support their detailed work in highlighting the need for prospective clinical registry to follow long term outcomes.
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The conundrum underlying this condition is likely due to the different pathologies amalgamated under the umbrella of syringomyelia and perhaps the clinician is better served considering the syrinx formation as an effect of the underlying pathology which then allows one to focus efforts on deciphering and treating the cause of the syringomyelia until some of the novel avenues being explored to prevent its occurrence translate into the clinical domain. B Roy Chaudhary 1, M. G. Fehlings 2. 1
B Roy Chaudhary, MBBS, MSC, FRCS Neurosurgery Spine Fellow, Toronto Western Hospital
2
Michael G. Fehlings, MD, PhD, FRCSC, FACS Professor of Neurosurgery, Halbert Chair in Neural Repair and Regeneration, Vice Chair Research, Department of Surgery, University of Toronto, Head, Spinal ProgrAM Toronto Western Hospital, University Health Network
ACCEPTED MANUSCRIPT
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REFERENCES:
Austin, J.W., Afshar, M. & Fehlings, M.G., 2012a. The Relationship between Localized Subarachnoid Inflammation and Parenchymal Pathophysiology after Spinal Cord Injury. Journal of Neurotrauma, 29(10), pp.1838–1849.
2)
Austin JW, Kang CE, Baumann MD, DiDiodato L, Satkunendrarajah K, Wilson JR, Stanisz GJ, Shoichet MS, Fehlings MG. Biomaterials. Biomaterials. 2012;33(18):4555–4564. doi:10.1016/j.biomaterials.2012.03.022.
3)
Backe HA, Betz RR, Mesgarzadeh M, Beck T, Clancy M. Post-traumatic spinal cord cysts evaluated by magnetic resonance imaging. Paraplegia. 1991;29(9):607–612. doi:10.1038/sc.1991.89.
4)
Brodbelt, A.R. & Stoodley, M.A., 2003. Post-traumatic syringomyelia: a review. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 10(4), pp.401–408.
5)
Chang HS, Tsuchiya T, Fujisawa N, Oya S, Matsui T. Syringomyelia associated with arachnoid septum at the craniovertebral junction, contradicting the currently prevailing theory of syringomyelia formation. Acta Neurochirurgica. 2011;154(1):141–145. doi:10.1007/s00701-011-1211-2.
6)
Chern JJ, Gordon AJ, Mortazavi MM, Tubbs RS, Oakes WJ. Pediatric Chiari malformation Type 0: a 12-year institutional experience. J Neurosurg Pediatr. 2011;8(1):1–5. doi:10.3171/2011.4.PEDS10528.
7)
Fehlings, M.G. & Austin, J.W., 2011. Posttraumatic syringomyelia. Journal of Neurosurgery: Spine, 14(5), pp.570–2– discussion 572.
8)
GARDNER, W.J., 1965. HYDRODYNAMIC MECHANISM OF SYRINGOMYELIA: ITS RELATIONSHIP TO MYELOCELE. Journal of Neurology, Neurosurgery & Psychiatry, 28, pp.247–259.
9)
George M Ghobrial MD, Richard T Dalyai MD, Mitchell G Maltenfort P, Srinivas K Prasad MD, James S Harrop MD, Ashwini D Sharan MD. Accepted Manuscript. World Neurosurg. 2014:1–22. doi:10.1016/j.wneu.2014.06.044.
10)
Heiss JD, Suffredini G, Bakhtian KD, Sarntinoranont M, Oldfield EH. Normalization of hindbrain morphology after decompression of Chiari malformation Type I. Journal of Neurosurgery. 2012;117(5):942–946. doi:10.3171/2012.8.JNS111476.
11)
Milhorat, T.H., 2000. Classification of syringomyelia. Neurosurgical FOCUS, 8(3), p.E1.
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1)
ACCEPTED MANUSCRIPT
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. Journal of Neurosurgery. 1994;80(1):3–15. doi:10.3171/jns.1994.80.1.0003.
13)
Perrin, R.G. & Fehlings, M., 2004. The etiology of syringomyelia in association with lesions of the foramen magnum. Journal of the Neurological Sciences, 220(1-2), pp.1–2.
14)
Portal, A., Cours d’Anatomie Medicale.Paris: Beaudoin, 1803,
15)
Seki, T. & Fehlings, M.G., 2008. Mechanistic insights into posttraumatic syringomyelia based on a novel in vivo animal model. Journal of Neurosurgery: Spine, 8(4), pp.365–375.
16)
Shaw TA, McGonnell IM, Driver CJ, Rusbridge C, Volk HA. Increase in Cerebellar Volume in Cavalier King Charles Spaniels with Chiari-like Malformation and Its Role in the Development of Syringomyelia. Sugihara I, ed. PLoS ONE. 2012;7(4):e33660. doi:10.1371/journal.pone.0033660.t002.
17)
Williams, B., 1981. Simultaneous cerebral and spinal fluid pressure recordings. 2. Cerebrospinal dissociation with lesions at the foramen magnum. Acta Neurochirurgica, 59(1-2), pp.123–142.
18)
Wyndaele, M. & Wyndaele, J.-J., 2006. Incidence, prevalence and epidemiology of spinal cord injury: what learns a worldwide literature survey? Spinal cord, 44(9), pp.523–529.
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ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT
Highlights
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Syringomyelia is estimated to affect 9 per 100,000 of the population It occurs in association with a spectrum of clinical conditions A unifying pathophysiological basis for syringomyelia continues to be elusive. Due to this, the choice of intervention becomes an intra-operative decision. The clinician should consider syrinx formation as an effect of underlying pathology
AC C
• • • • •
S1878-8750(14)00754-2
DOI:
10.1016/j.wneu.2014.08.033
Reference:
WNEU 2524
To appear in:
World Neurosurgery
Received Date: 25 July 2014 Accepted Date: 15 August 2014
Please cite this article as: Chaudhary BR, Fehlings MG, Adult-Onset Syringomyelia - From theory to practice and beyond, World Neurosurgery (2014), doi: 10.1016/j.wneu.2014.08.033. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT PERSPECTIVES
Michael G. Fehlings, M.D. Toronto Western Hospital 399 Bathurst St. West Wing, 4-449 Toronto, ON Canada M5T 2S8 Ph. 416-603-5627 Email: [email protected]
RI PT
Adult-Onset Syringomyelia - From theory to practice and beyond
M AN U
SC
Syringomyelia is a rare neurological disorder estimated to affect 9 per 100,000 of the population [4] resulting from pathological cyst formation within the spinal cord. The classic presentation includes a dissociated and/or suspended progressive sensory loss in a cape like distribution with spasticity, lower limb hyperreflexia and neuropathic pain. However syringomyelia occurs in association with a spectrum of clinical conditions, variable spinal cord anatomical localization and diverse histopathological patterns. To reflect this it can be classified as [11] : 1) Communicating central canal syrinx 2)Non-Communicating central canal syrinx 3)Atrophic cavitations 4)Neoplastic cavitations.
EP
TE D
Amongst adult cases approximately 50% of syringomyelia is associated with Chiari 1 malformations whilst the of the remainder of cases are considered acquired with 25% being associated with spinal cord trauma (post traumatic syringomyelia) or arachnoiditis which are all non-communicating central canal syringes [4]. Spinal cord injury (SCI) is an important pathology with a significant socio-economic burden [18] and upto 51% of these patients are reported to develop spinal cord cysts [3]. Symptomatic progression due to such post-traumatic syringomyelia (PTS) occurs in a smaller subset of SCI patients and can present with back pain, ascending sensory loss, autonomic dysreflexia, spasticity and worsening motor deficits.
AC C
Despite the first clinical and accompanying autopsy description of syringomyelia presenting as an abnormal cavity in the cervical spinal cord dating back to 1803 by Antoine Portal [14], a unifying pathophysiological basis for syringomyelia continues to be elusive. We have previously recapitulated the proposed theories [13] salient amongst which are those from Gardner [8], Williams [17] and Oldfield [12]. Many of the above reports explain the pathophysiology of the most common forms of syringomyelia i.e. those associated with Chiari malformations. In such cases surgical redress of the chiari malformation often provides clinical and radiological improvement [10]. However none of these proposed mechanisms explain all the variations in reported clinical cases and histopathological findings [5]. It is interesting to note that in some cases of syringomyelia with apparent absence of tonsillar decent typical of Chiari 1 malformations, contents of the posterior fossa are caudally compressed in the so called Chiari malformation Type 0 [6]. Even more remarkable is that such co-relation is borne out in other mammalian species such as the Cavalier King Charles Spaniel dog breed amongst which almost half the population over 4 years of age has syringomyelia [16].
ACCEPTED MANUSCRIPT
SC
RI PT
In non-Chiari syringomyelia such as PTS, In-vivo animal models [15] demonstrate that the combination of SCI (by clip application) and subarachnoid kaolin injection to induce arachnoid scarring results in a significantly greater syrinx formation and perilesional myelomalacia than SCI alone. This supports the role of altered fluid dynamics and pathological subarachnoid CSF flow being propagated into the medullary tissues along the extracellular compartment subsequent to an initial ‘syrinx generating ictus’ such as secondary pathological mechanisms following spinal cord injury [7]. The PTS group also demonstrated greater parenchymal inflammation and scarring relative to the SCI alone as evidenced by significant increases in cytokine (IL-1α, IL-1β) and chemokine (MCP-1, GRO/KC and MIP-1α) production confirming the potentiation of parenchymal pathophysiology by arachnoiditis [1]. Of note is the reduction of post-traumatic parenchymal fibrous scar formation in these animal evidenced by reduced Chondritin Sulphate ProteoGlycan (CSPG) deposition and reduced IL-1α levels when a hydrogel of hyaluronan and methy cellulose (HAMC) was injected into the subarachnoid space 24hrs post PTS induced injury to reduce inflammation17. This provides for the basis for one of the possible options [7] for clinical intervention in patient who maybe at greater risk of developing PTS after SCI.
EP
TE D
M AN U
In this issue, Ghobrial et al [9] present a detailed systematic review of the outcomes of arachnolysis or CSF diversion in syrinomyelia patients presenting to adult neurosurgical practice. To best inform clinical practise pertaining to the choice of arachnolysis or CSF diversion, they have excluded studies that prima facia deal with chiari related syringomyelia which form a significant proportion of syringomyelia patients. However due the heterogeneity and paucity of prospective studies on the topic the selection of review articles still result in 27 percent of patients having Chiari malformations as the authors acknowledge. An additional difficulty for surgical planning is the absence of pre-operative diagnostic imaging to confirm arachnoid adhesions with various reports detailing occult arachnoid lesions in syringomyelia patients which were demonstrated only surgically [5]. Thus the choice of intervention becomes ultimately an intra-operative decision. We therefore agree with the authors that these factors make it difficult to generalize these findings for recommendations for the treatment of non-Chiari related syringomyelia. We also support their detailed work in highlighting the need for prospective clinical registry to follow long term outcomes.
AC C
The conundrum underlying this condition is likely due to the different pathologies amalgamated under the umbrella of syringomyelia and perhaps the clinician is better served considering the syrinx formation as an effect of the underlying pathology which then allows one to focus efforts on deciphering and treating the cause of the syringomyelia until some of the novel avenues being explored to prevent its occurrence translate into the clinical domain. B Roy Chaudhary 1, M. G. Fehlings 2. 1
B Roy Chaudhary, MBBS, MSC, FRCS Neurosurgery Spine Fellow, Toronto Western Hospital
2
Michael G. Fehlings, MD, PhD, FRCSC, FACS Professor of Neurosurgery, Halbert Chair in Neural Repair and Regeneration, Vice Chair Research, Department of Surgery, University of Toronto, Head, Spinal ProgrAM Toronto Western Hospital, University Health Network
ACCEPTED MANUSCRIPT
RI PT
REFERENCES:
Austin, J.W., Afshar, M. & Fehlings, M.G., 2012a. The Relationship between Localized Subarachnoid Inflammation and Parenchymal Pathophysiology after Spinal Cord Injury. Journal of Neurotrauma, 29(10), pp.1838–1849.
2)
Austin JW, Kang CE, Baumann MD, DiDiodato L, Satkunendrarajah K, Wilson JR, Stanisz GJ, Shoichet MS, Fehlings MG. Biomaterials. Biomaterials. 2012;33(18):4555–4564. doi:10.1016/j.biomaterials.2012.03.022.
3)
Backe HA, Betz RR, Mesgarzadeh M, Beck T, Clancy M. Post-traumatic spinal cord cysts evaluated by magnetic resonance imaging. Paraplegia. 1991;29(9):607–612. doi:10.1038/sc.1991.89.
4)
Brodbelt, A.R. & Stoodley, M.A., 2003. Post-traumatic syringomyelia: a review. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 10(4), pp.401–408.
5)
Chang HS, Tsuchiya T, Fujisawa N, Oya S, Matsui T. Syringomyelia associated with arachnoid septum at the craniovertebral junction, contradicting the currently prevailing theory of syringomyelia formation. Acta Neurochirurgica. 2011;154(1):141–145. doi:10.1007/s00701-011-1211-2.
6)
Chern JJ, Gordon AJ, Mortazavi MM, Tubbs RS, Oakes WJ. Pediatric Chiari malformation Type 0: a 12-year institutional experience. J Neurosurg Pediatr. 2011;8(1):1–5. doi:10.3171/2011.4.PEDS10528.
7)
Fehlings, M.G. & Austin, J.W., 2011. Posttraumatic syringomyelia. Journal of Neurosurgery: Spine, 14(5), pp.570–2– discussion 572.
8)
GARDNER, W.J., 1965. HYDRODYNAMIC MECHANISM OF SYRINGOMYELIA: ITS RELATIONSHIP TO MYELOCELE. Journal of Neurology, Neurosurgery & Psychiatry, 28, pp.247–259.
9)
George M Ghobrial MD, Richard T Dalyai MD, Mitchell G Maltenfort P, Srinivas K Prasad MD, James S Harrop MD, Ashwini D Sharan MD. Accepted Manuscript. World Neurosurg. 2014:1–22. doi:10.1016/j.wneu.2014.06.044.
10)
Heiss JD, Suffredini G, Bakhtian KD, Sarntinoranont M, Oldfield EH. Normalization of hindbrain morphology after decompression of Chiari malformation Type I. Journal of Neurosurgery. 2012;117(5):942–946. doi:10.3171/2012.8.JNS111476.
11)
Milhorat, T.H., 2000. Classification of syringomyelia. Neurosurgical FOCUS, 8(3), p.E1.
AC C
EP
TE D
M AN U
SC
1)
ACCEPTED MANUSCRIPT
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. Journal of Neurosurgery. 1994;80(1):3–15. doi:10.3171/jns.1994.80.1.0003.
13)
Perrin, R.G. & Fehlings, M., 2004. The etiology of syringomyelia in association with lesions of the foramen magnum. Journal of the Neurological Sciences, 220(1-2), pp.1–2.
14)
Portal, A., Cours d’Anatomie Medicale.Paris: Beaudoin, 1803,
15)
Seki, T. & Fehlings, M.G., 2008. Mechanistic insights into posttraumatic syringomyelia based on a novel in vivo animal model. Journal of Neurosurgery: Spine, 8(4), pp.365–375.
16)
Shaw TA, McGonnell IM, Driver CJ, Rusbridge C, Volk HA. Increase in Cerebellar Volume in Cavalier King Charles Spaniels with Chiari-like Malformation and Its Role in the Development of Syringomyelia. Sugihara I, ed. PLoS ONE. 2012;7(4):e33660. doi:10.1371/journal.pone.0033660.t002.
17)
Williams, B., 1981. Simultaneous cerebral and spinal fluid pressure recordings. 2. Cerebrospinal dissociation with lesions at the foramen magnum. Acta Neurochirurgica, 59(1-2), pp.123–142.
18)
Wyndaele, M. & Wyndaele, J.-J., 2006. Incidence, prevalence and epidemiology of spinal cord injury: what learns a worldwide literature survey? Spinal cord, 44(9), pp.523–529.
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ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT
Highlights
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M AN U
SC
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Syringomyelia is estimated to affect 9 per 100,000 of the population It occurs in association with a spectrum of clinical conditions A unifying pathophysiological basis for syringomyelia continues to be elusive. Due to this, the choice of intervention becomes an intra-operative decision. The clinician should consider syrinx formation as an effect of underlying pathology
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