Mechanism of severe neurologic complications after steroid epidural injections. Jean-Denis Laredo & Hervé Bard

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1 Mechanism of severe neurologic complications after steroid epidural injections Jean-Denis Laredo & Hervé Bard

2 Mechanism of severe neurologic complications after steroid epidural injections Different for cervical versus lumbar steroid epidural injections

3 Mechanism of severe neurologic complications after steroid epidural injections Cervical steroid epidural injections Epidural hematoma Intramedullary injection Infection Spinal cord infarction due to vascular ischemia

4 1/ cerebellar infarct: Vertebral artery territory 2/ Cervical spinal cord infarct: Cervical radiculo-medullary artery

5 Lumbar epidural steroid injection (LESI)

6 Mechanism of severe neurologic complications after steroid epidural injections Cervical steroid epidural injections Lumbar steroid epidural injections Spinal cord infarction due to vascular ischemia

7 MRI: 6 hours post 24hours

8 Variability of the infarct extent

9 A constant finding in permanent neurologic deficits complicating Lumbar ESI: spinal cord-conus medullaris vascular infarction

10 Arterial supply of the spinal cord One main anterior spinal artery Supplied by 5 to 7 Radiculomedullary arteries Two posterolateral arteries Anterior view posterior view

11 Arterial supply to the spinal cord 32 pairs of metameric radicular arteries 3 kind of metameric radicular arteries 5 to 7 Radiculo-medullary arteries, supplying the anterior and the 2 posterolateral spinal arteries Radiculo-pial arteries participating to the vasa corona, metameric distribution Plain metameric radicular arteries

12 Arterial supply of the spinal cord All the arterial supply to the spinal cord is provided by radiculo-medullary arteries penetrating the spinal canal through an intervertebral foramen

13 Arterial supply to the lumbosacral spinal cord and conus terminalis In 75% of cases the radiculomedullary artery (RMA) of the lumbosacral cord and conus terminalis (Adamkiewicz artery) arises between T9 and T12, and from the left in 69% of the cases. When the Adamkiewicz artery arises above T9, there is usually an additional lumbar or sacral RMA (Desproges- Gotteron artery).

14 Arterial supply to the lumbar spinal cord Consequences for lumbosacral steroid injections All the lumbar and anterior sacral intervertebral foramens, especially on the left side, may contain a radicular artery participating to the arterial supply of the conus terminalis and eventually to the crucial arcade

15 Arterial supply to the conus medullaris Anse anastomotique remarquable ( crucial arcade ), around the conus terminalis, similar to Willis polygon, which anastomoses the anterior with the 2 posterolateral spinal arteries

16 Mechanism of severe neurologic complications after steroid epidural injections Pathogenesis of the spinal cord infarction : Arterial rather than venous pathway Thrombosis Vasospasm Vascular compression Vascular embolization by steroid aggregates Tiso RL et al, Spine J (2004) Okabadejo GO et al, JBJS (2008)

17 Neurologic deficits after LESI Common clinical findings Indication of the LESI : sciatica or femoral pain (&LBP) due to degenerative disease Fluoroscopy or CT guidance After a few seconds/minutes: Intense abdominal &/or leg pain Sometimes malaise and flush Followed by rapid installation of the motor deficit

18 Neurologic deficits after LESI on a post-op spine 8 cases among 12 (66,6%) LESI on a post-op spine: only 8% of LESI in our institution Needle approach : 6 foraminal, 1 interlamar, 1 apophyseal joint injections Review of 6 cases : needle tip close to the scar 6/6 Intervertebral level: L1-2, L3-4, L4-5, L5-S1 Side: 7G, 1D Wybier M et al, Eur Radiol 2010

19 Neurologic deficits after LESI on a post-op spine Role of the postoperative epidural scar? prior contrast inj. post contrast inj.

20 + + = Tiso RL et al, The spine J, 2004

21 Permanent neurologic deficits following LESI (n=12) Steroid suspension Elementary particule size (µ)* Tendancy to coalesce* Aggregate size (µ)* Prednisolone acetate France (n=6) Hydrocortancyl R Betamethasone acetate USA (n=1) Celestone Solupsan R Celestone Chronodose R Betnesol R USA (n=2) Triamcinolone acetonide UK (n=1) Kenalog R, Kenacort R Tedarol R USA (n=2) Methylprednisolone acetate Depomedrol R

22 Steroid suspensions Aggregate size USA Depomedrol R >50µ: 25% >1000µ: 5% Kenalog R >50µ: 25% >1000µ: 1% Celestone Solupsan R >50µ: 25% >1000µ: 0% France Hydrocortancyl 125 R mean µ Altim R few small aggregates Benzon H, Anesthesiology 2007 Tiso RL, The Spine J, 204 Roques CF, Rhumatologie 1987

23 Steroid suspensions Tendancy to form particule aggregates USA Depomedrol R ++ Kenacort R, Kenalog R ++ Celestone Solupsan R + France Hydrocortancyl 125 R ++++ Altim R + Benzon H, Anesthesiology 2007 Tiso RL, The Spine J, 204 Roques CF, Rhumatologie 1987

24 Mechanism of severe neurologic complications after LSEI Spinal cord infarction due to vascular ischemia Pathogenesis hypotheses 1. Obliteration of a radiculomedullary artery by aggregates of steroid particles 2. Deformation and agglutination of Red Blood cells when mixed with particulate steroids

25

26 Red Blood cells agglutination when mixed with particulate steroids: RBC agglutination GROUPE SANGUIN A AB O ALTIM HYDROCORTANCYL KENALOG DEPOMEDROL

27

28

29

30 Pathway of the steroid to the spinal cord 1. Radiculo-medullary artery 2. Unknown arteriovenous fistula 2 février Rupture altim - infiltration épidurale 50

31 Normal arteriovenous anastomoses Nerve roots receive en arterial supply from both ends through longitudinal peri- and intraradicular arteries that anastomose in the midsections of the radicular fascicules. Numerous and relatively large normal arteriovenous anastomoses throughout the length of each root protect the functionnal integrity of the radicualr circulation in the event of focal compressions Role of epidural and radicular veins in chronic back pain and radiculopathy. Wesley W Parke. In: Arthroscopic and Endoscopic Spinal Surgery. Ed: kambin P. Humana Press Inc. Totowa, NJ 53

32 2 février Rupture altim - infiltration épidurale 54

33 2 février Rupture altim - infiltration épidurale 55

34 56

35 57

36 Pathway of the steroid to the spinal cord 1. Radiculo-medullary artery 2. Unknown arteriovenous fistula 3. Venous pathway? May explain neurologic complications after posterior (interlaminar/interspinous) epidural injections in the postoperative spine 2 février Rupture altim - infiltration épidurale 58

37 addendum

38 Etude Study formate Biais Evaluation Results Kennedy et al RCT Unilateral NRP Unilevel HD Kim & Brown 2011 RCT Park et al 2010 El Yagouchi 2013 RCT Triamcinolone vs DXM Foraminal 106 pts Retrospective 3645 foraminal 78 pts total 30 pts total N inj Surgery VAS NS but 1.6 inj for DXM Vs 1.4 for TC.17% DXM vs1% TC needed 3inj NS but Trend toward less relief & shorter duration TC: at 1M DXM: (stat si) McGill pain,odi: no diff NS

39 Dreyfus et al RCT Cervical NS Ahadian FM et al. Reg Anesth Pain Med 2011;36:572 Kim et al. Clin J Pain Mehta et al. PM R DXM 4/8/12mg Sequential Triamcinolone then DXM Review Delayed oral patient interview Patient preference Inj-free interval Pain, function No differences Higher % pts prefer TC Inj-free interval 91d/77 Disc Hern 105days/78 Foram app 89days/67 NS Shakir et al. Am J Phys Med Rehabil Sep. Lee et al. Skeletal Radiol Nov. Cohort VAS NS Cohort VAS NS

40 Paraplegia complicating caudal epidural steroid injection Somanchi BV,Mohammad S, Ross R. An unusual complication following caudal epidural steroid injection: a case report. Acta Orthop Belg 2008; 74(5):720-2

41 Paraplegia complicating DXM epidural steroid injection Gharibo C, Fakhry M, Diwan S, Kaye AD. Conus medullaris infarction after a right L4 transforaminal epidural steroid injection using dexamethasone. Pain Physician 2016;19:E1211-E1214 Man 60yo. NRP for 3 years. No previous surgery L4 Transforaminal injection of Dexamethasone (exact brand not provided)

42 PEG BENZYLIC A. PARABEN BISULFITES DEPOMEDROL Méthylprédnisolone acétate KENALOG Triamcinolone acétonide KENACORT CELESTONE SOLUSPAN Triamcinolone acétonide Bétamétasone Sodium phosphate DIPROSTENE Bétamétasone Sodium phosphate ALTIM Cortivazol DECADRON Dexaméthasone sodium phosphate

43 STOP

44

45

46 Analyse des 12 cas: - 7M et 5F - 58 ans (40-78), médiane 64 ans - 8 rachis opérés et 4 rachis non opérés - 10 injections du côté gauche, 2 à droite - 10 foraminales, 1 interlamaire, 1 para-articulaire postérieure - T12-L1 (n=1) L1-2 (n=1) L2-3 (n=1) L3-4 (n=3) L4-5 (n=3) L5-S1 (n=3) Wybier M et al. Eur Radiol 2010

47

48 SANOFI CLINICAL TRIAL Main proposal Alternative/compl Adult Adult Clinical indication Acute-subacute NRP (leg pain>back pain) due to HD Spinal stenosis Plurirad/monorad Pain duration Min- Max: 2W to 3M Min- Max: 3W to 6M Spine approach Interlaminar (W palmer technique) Foraminal Treatment 1/Epidural Lidocaïne 2/DXM no excipient Epidural saline Subcutaneous saline Particulate No excipient Primary endpoint Pain (VAS) Second: need for add injections /cross-over Timeline 1W, 3W And 6W Cross-over Yes after 3W No Yes after 6W

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