Tethered cord release in EDS: - PowerPoint Presentation

1. Tethered cord release in EDS: A practical approach to understanding surgical criteria and supporting data outcomesPetra M Klinge MD PhDAssociate Professor of Neurosurgery Dept. of Neurosurgery Rhode Island HospitalWarren Alpert Brown Medical SchoolProvidence RI

2. Tethered cord Syndrome in EDSUrology, GI, GynecologyOrthopedic surgery, Plastic surgeryInternal Medicine(Cardiology, Allergology, Endocrinology)GeneticsPain management Nursing careAnesthesiaPhysical therapySocial workNeuroPathologyNeuroimagingNeurology/PediatriciansNutritionOrthoticsRheumatologyNeurosurgeryPsychology

3. OverviewRECAP_ Occult Tethered cord syndrome (OTCS) Supporting Evidence of OTCS in EDSSymptoms and clinical findingsSurgical findings and observationsSurgical outcome(s)Histological findings after Filum resectionPractical approach and decision tree to surgical indication and management of tethered cord syndrome in EDS Areas of research

4. A clinical syndrome of tethered cord… with little radiographic evidence> 6 months of age: Conus at level Th12 to upper L2No FAT SIGNAL at and below the conus!

5. A clinical syndrome of tethered cord….SUBJECTIVE : Back pain and leg pain(s) and complain(s): “aches” and “burns” not sharp “heavy” “stiff and tight” “traveling” no radiatingNEURO: LE signsInfants_Decreased leg movement, absent reflexesToddler_Abnormal gait or delayed walking (“intoeing”, “loss of ankle control”)Teenager_Pain, Asymmetrical motor dysfunctionYoung adults_Pain, Spasticity and HyperreflexiaUROLOGY/GI: Neurogenic bladder*, Frequent Urinary tract infection (> 3 per year), Incontinence, ConstipationORTHO: Foot and leg deformities and asymmetry, progressive Scoliosis, kyphosis, delayed or plateau in growth

6. Childs Nerv Syst. 2013 Sep;29(9):1635-40.Occult tethered cord syndrome: a review. Tu A1, Steinbok P.

7. The occult tethered cord syndrome and surgical indication - PEDsNeuroOrthoUro/GI“ Progressive” SyringohydromeliaFilum > 2mmin axial section¾ clinical qualifiers mandatory for surgical indication!2/4 qualifiers acceptable with “positive” imaging findingsSpina bifida occultaDerm “Dimple”

8. Pediatr Neurosurg. 2004 Mar-Apr;40(2):51-7;Occult tight filum terminale syndrome: results of surgical untethering.Wehby MC1, O'Hollaren PS, Abtin K, Hume JL, Richards BJ.Divisions of Pediatric Neurosurgery and Pediatric Urology, Emanuel Children's Hospital, Portland, Oreg., USA. monicawehby@hotmail.comThe entity of an occult tight filum terminale syndrome, characterized by clinical findings consistent with a tethered cord syndrome, but with the conus ending in a normal position and Filum > 2mm but no fatty infiltration. N= 60 children (ages 3-18 years) followed for more than 6 months (mean 13.9 months). The criteria for surgical intervention were (1) Bifid lumbar spine (2) progressive bladder instability unresponsive to conservative measures, (3) urological/nephrological evaluation to confirm neurogenic etiology, and (4) two or more of the following: (a) bowel involvement (fecal incontinence or chronic constipation), (b) lower extremity weakness, (c) gait changes, (d) reflex/tone abnormalities, (e) sensory disturbances, (f) back/leg pain, (g) orthopedic abnormalities/limb length discrepancy, (h) scoliosis/lordosis, (i) recurrent urinary tract infections, (j) abnormal voiding cystourethrogram/ultrasound, (k) syringomyelia, and (l) neurocutaneous stigmata. Postoperatively, urinary incontinence/retention showed complete resolution in 52%, marked improvement (>95% resolution) in 35%, moderate improvement (>75%) in 6%, minimal improvement (> 50%) in 6%, and no improvement (<50%) in 2%. Fecal incontinence completely resolved in 56%, improved in 41%, and was unchanged in 3%. Weakness, sensory abnormalities, and pain improved or resolved in all patients.

9. OverviewRECAP_ Occult Tethered cord syndrome (OTCS) Supporting Evidence of OTCS in EDSSymptoms and clinical findingsSurgical findings and observationsSurgical outcome(s)Histological findings after Filum resectionPractical approach and decision tree to surgical indication and management of tethered cord syndrome in EDS Areas of research

10. The occult tethered cord syndrome in EDS (n=8; 2014 to 2015, 3 to 39 yrs)NeuroOrthoUro/GIDermIncreased frequency of joint subluxation (LE and UE) and progression of other musculoskeletal manifestations including peripheral neuropathy with traveling pain , M. Castori, N. Voermans: Neurological manifestations of Ehlers Danlos syndrome(s): A review. Iran J Neurol 2014Craniocervical Manifestations Upgrading of braces AFO to KFOPelvic weakness and instabilityIncreased and decreased bladder compliance* Predictor for occult tethered cord in EDS?

11. Case presentations: # 1 M, 5yrsInconsolable from pain (back and leg) Progressive weakness in ankles and knees (upgrade in braces)Progressive Urinary leakageUrodynamic studies under Anesthesia “grossly normal”#2 F, 18 yrs Progressive “Chiari pain”(3mm Chiari)Leg “aches” and weaknessProgressive scoliosisReduced bladder capacity and low compliance (Urodynamic studies)

12. #1 MRI L2 – 3 Interlaminectomy

13. #1 intraop findings

14. #2 MRI NORMAL T2 MRI conus position NO T1 MRI axial “fat” signal L2 – 3 Interlaminectomy

15. # 2 intraop findings

16. Intraoperative findings in EDS_varia#7 EDS, f, adult4 EDS f, adult##8 EDS, f, adult

17. OverviewRECAP_ Occult Tethered cord syndrome (OTCS) Supporting Evidence of OTCS in EDSSymptoms and clinical findingsSurgical findings and observationsSurgical outcome(s)Histological findings after Filum resectionPractical approach and decision tree to surgical indication and management of tethered cord syndrome in EDS Areas of research

18. Case presentations: # 1 M, 5yrs_ 3 months outcomeInconsolable from pain (back and leg) Progressive weakness in ankles and knees (upgrade in braces)Progressive Urinary leakageUrodynamic studies under Anesthesia “grossly normal”#2 F, 18 yrs_ 3 months outcome Progressive “Chiari pain”(3mm Chiari)Leg “aches” and weaknessProgressive scoliosisReduced bladder capacity and low compliance (Urodynamic studies)

19. EDS improvement (n=8) SUBJECTIVE: Improved Leg numbness and pain (“feeling of legs”)URO: Reduced “Leaking” of bladder and improved bladder controlORTHO: Improved thoracic posture and associated chest pain; Functional joint deformities and joint subluxations (“ less curling of toes”)NEURO: “Chiari and Craniocervical symptoms”; Improved Balance and reduced falling spells; Improved pelvic stability; Reduced joint subluxations and “facilitated” Physical therapy

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21. Parameters of Study:84 surveys were mailed out or handed out in the office to patients who had undergone a tethered cord procedure at least 10 months ago. 30 surveys were returned (response rate 36%) Surgery dates ranging from June 2010-December 2014. All respondents were women whose ages at the time of the procedure ranged from 15-60 (average age 30.5). All 30 found to have some form of Ehlers Danlos Syndrome.TETHERED CORD SURVEY (F. HENDERSON)

22. Level of Pain%Pre Surgery (n=29)%Post Surgery (n=29)003% (1/29)0.5-2.5020% (6/29)3-4.5030% (9/29)5-6.520% (6/29)17% (5/29)7-8.552%( 15/29)27% (9/29)9-1028% (8/29)0Table # 2: Comparison of Low Back Pain (0-10 scale) Among Participants Pre Vs. Post Surgery(n=29, one patient did not have a pre-op pain score available for comparison.P=3.27539E-08Symptoms not showing statistically significant improvement: leg cramps, UTIs, trouble emptying bladder, urinary urgency, nocturia, bowel incontinence.

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24. OverviewRECAP_ Occult Tethered cord syndrome (OTCS) Supporting Evidence of OTCS in EDSSymptoms and clinical findingsSurgical findings and observationsSurgical outcome(s)Histological findings after Filum resectionPractical approach and decision tree to surgical indication and management of tethered cord syndrome in EDS Areas of research

25. Histology of an abnormal filum X40

26. Adipose tissue was associated with a conus level below the L2–3 disc space (OR 2.3, p = 0.031) and with a fatty filum on imaging (OR 9.8, p < 0.001). Nerve twigs were associated with abnormal urodynamics (OR 10.9, p = 0.049).

27. Histological Studies in OTCS (Rhode Island Hospital)H&E to grade the amount of fat, assess inflammatory and vascular pathologyTrichrome stain and Elastin stain to assess integrity of collagen vs. elastinElectron microscopic studies to evaluate the Collagen and Elastin fiber integrityImmunostaining for leucocytes (CD 45)microglia (CD 68)Activated mast cells (CD 117)Grading on longitudinal sectioned filum: Mild <10%, Moderate 10 – 50%, Heavy > 50%

28. Vascularity H&E EDSx4PMNs (Neutrophils) at blood vessel in4/5 EDS filumx10

29. Trichrome collagen vs. Elastin: EDS x20x10x20M, 5yF, 3y

30. EM: Collagen

31. Inflammation H&E

32. CD 45 Lymphocytes RS15-8252 B.W.Example for “scattered”X 20

33. CD 68 macrophages RS15-8252 B.W.x10x20x20

34. CD 117 activated Mastcells RS15-8252 B.W.

35. Toluidine staining (Mastcells) RS15-8252 B.W. Specific purple staining in Mast cellsX 40

36. Toluidine staining (EDS) RS15-12342 P.W.X 10X40

37. Histological Results (n= 5 EDS)1=mild <10%2=moderate 10-50%3=heavy >50%Caseadipose tissue (H&E)Vascularity (H&E)Inflammation (H&E)Collagen Trichrome (fibrosis)Elastin stainCD 45CD68CD117 (ependyma, neural elements)RS15-8252 B.W.2113 1 (irregular)Scattered +1 +Mastcells 3+RS14-17467 M.S.12131 (irregular)-rare +RS15-3744 J.C.12131(irregular)-- Mastcells 1+RS15-8707 A.R.12131 (irregular)-rare +RS15-12342 P.W.11131 (irregular)Mastcells 3+RS13-9698 J.E.21132 (regular)Scattered +Scattered +RS12-10307 M.B.31132 (regular)Scattered +Scattered +Mastcells 1+RS15-7907 H.S.21132 (regular)Scattered +Scattered +Mastcells 1+RS13-9081 V.L.11132(regular)-rare +RS11-14195 S.M.11132 (regular)rare +-RS11-8795 G.S.11132 (regular)rare +rare +RS13-12349 T.M.12132 (regular)rare +rare +Mastcells 1+Michael Punsoni , Department of Neuropathology, Rhode Island Hospital

38. Summary: Supporting Evidence Intraoperative findings are inconsistent with the radiographic findings, and often show more pronounced pathology, i.e. significant thickening and fatty infiltration and vascularity. The filum is inconsistently taught. Besides the histological support of classical abnormal findings, there are abnormal cluster (s) of inflammation (CD 68, CD 45). Vascular penetration of polymorphonuclear neutrophils (PMNs) associated with Mast cells (CD 117), EDS with abnormally structured and disintegrating collagen in EM and disorganized Elastin. OUTCOME: OTSC shows the overall improvement in all dimensions of the clinical syndrome

39. OverviewRECAP_ Occult Tethered cord syndrome (OTCS) Supporting Evidence of OTCS in EDSSymptoms and clinical findingsSurgical findings and observationsSurgical outcome(s)Histological findings after Filum resectionPractical approach and decision tree to surgical indication and management of tethered cord syndrome in EDS Areas of research

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41. Algorithm for surgical decision making: PROPOSAL RIEDS with OTCS CRITERIAChecklist of Qualifiers (DERM, URO, Neuro, Ortho): 3/4qualifiers with bladder or bowel signs and symptoms supported by Urodynamic studiesIf 3/4 qualifiers without bladder and bowel signs: Mandate of positive standard imaging If 2/4: mandatory bladder or bowel signs and symptoms supported by Urodynamic studies + positive standard imagingConsider Comorbities (not as exclusion criteria):POTS, CCI, MCAS, PREVIOUS SURGERIES and UROLOGICAL AND GYNEKOLOGICAL HISTORYPROGRESSION of OTCS SYMPTOMS within last 6 months?YESNoSurgical TCRMonitoring

42. Imaging of tethered cord in EDS? UPRIGHT MRI FLEXION EXTENSION MRI

43. Guidelines and Consensus statement: Work in progressConsensus Statement proposed at the Chiari Syringomyelia Foundation Colloquium_ New Orleans 9_25_15CONSENSUS STATEMENT _Tethered cord syndrome Tethered cord syndrome: Progressive weakness and sensory impairment of the lower extremities, back and leg pain, neurogenic bladder (and bowel symptoms) are elements that should prompt consideration of Tethered Cord syndrome Tethered cord syndrome is a clinical diagnosis, based upon complete history, thorough neurological examination and thorough review of urodynamic and radiological findings, preferably in a multispecialty team The diagnosis of tethered cord syndrome should consider coexisting co-morbidities that may confound the clinical diagnosis, i.e. disorders of the craniocervical junction, the cervical, thoracic and lumbar spine, such as Chiari malformation, compression of the spinal cord by stenosis, disc or other pathologies, spinal deformity or instability, genetic disorders, and medical disorders such as Multiple sclerosis, diabetes mellitus The diagnosis of tethered cord syndrome requires:  The patient is moderately or severely disabled as a result of the following symptoms that may present in combination or in isolation  Symptoms ofLow back pain, andLeg pain and weakness and sensory deficits, andUrinary incontinence or bowel dysfunction Findings on examination of Leg weakness, and Sensory impairment in the lower extremity/iesDiagnosis of neurogenic bladder preferably confirmed by urodynamic testingA radiological assessment with is suggestive of tethered cord syndrome by ruling out other likely causes of the above findingsA reasonable assessment that he above findings are not part of other medical illness (as reviewed under 3.)  Other clinical findings should be present, including some of the following: sacral dimple or neurocutaneous markers, stretch signs (stretching cauda equine or cord increases pain and sensory deficits), flat feet, hammer toes, hyper-reflexia of the lower extremities, changes in tone of the lower extremities, foot and knee varus and valgus deformities and/or scoliosis Radiological findings may include some of the following: low lying conus, scoliosis, syringohydromyelia, spina bifida occulta, fatty or thickened filum (>2mm), obvious tethering of the neural elements that may be assess with a prone and supine lumbar MRI to assess conus movement and movement of the cauda equina 

44. OverviewRECAP_ Occult Tethered cord syndrome (OTCS) Supporting Evidence of OTCS in EDSSymptoms and clinical findingsSurgical findings and observationsSurgical outcome(s)Histological findings after Filum resectionPractical approach and decision tree to surgical indication and management of tethered cord syndrome in EDS Areas of research

45. Tethered cord in EDSIn chronic disease states, microglia respond more vigorously to systemic inflammatory stimulation f (“pro-inflammatory state”) The inflammatory changes appear relevant to tethered cord in EDSIf so: “Inflammed filum vs. fatty filum “ or “Filum mirrors the neurological manifestation”?Is tethered cord in EDS an “acquired condition” vs. congenital?

46. “If you cannot connect the issues, think of connective tissues”