mechanism of severe neurologic complications after steroid ... · complications after steroid...

Mechanism of severe neurologic

complications after steroid epidural injections

Jean-Denis Laredo

&

Hervé Bard

Mechanism of severe neurologic complications

after steroid epidural injections

• Different for cervical versus lumbar steroid

epidural injections

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

2/ Cervical spinal cord infarct:

Cervical radiculo-medullary artery

1/ cerebellar infarct:

Vertebral artery territory

Lumbar epidural steroid injection (LESI)

Mechanism of severe neurologic

complications after steroid epidural injections

• Cervical steroid epidural injections

• Lumbar steroid epidural injections

Spinal cord infarction due to vascular ischemia

MRI: 6 hours post 24hours

Variability of the infarct extent

A constant finding in permanent neurologic

deficits complicating Lumbar ESI:

spinal cord-conus medullaris vascular infarction

Arterial supply of the

spinal cord

• One main anterior spinal artery Supplied by 5 to 7 Radiculo-

medullary arteries

• Two posterolateral arteries

Anterior view posterior view

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

• All the arterial supply to the spinal cord is provided

by radiculo-medullary arteries penetrating the

spinal canal through an intervertebral foramen

Arterial supply of the spinal cord

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).

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”

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

Pathogenesis of the spinal cord infarction : Arterial rather than venous pathway

Thrombosis

Vasospasm

Vascular compression

Vascular embolization by steroid aggregates

Mechanism of severe neurologic

complications after steroid epidural injections

Tiso RL et al, Spine J (2004)

Okabadejo GO et al, JBJS (2008)

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

• 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

Neurologic deficits after LESI on a post-op

spine

prior contrast inj. post contrast inj.

Neurologic deficits after LESI on a post-op spine

Role of the postoperative epidural scar ?

+

=

+

Tiso RL et al, The spine J, 2004

Permanent

neurologic

deficits

following

LESI (n=12)

Steroid suspension Elementary

particule

size (µ)*

Tendancy to

coalesce*

Aggregate

size (µ)*

France (n=6)

Prednisolone acetate

HydrocortancylR

2-4

++++

30-120

USA (n=1)

Betamethasone acetate

Celestone SolupsanR

Celestone ChronodoseR

BetnesolR

10

+

20-30

USA (n=2)

UK (n=1)

Triamcinolone acetonide

KenalogR, KenacortR

TedarolR

2-4

++

40-80

USA (n=2)

Methylprednisolone

acetate

DepomedrolR

2

++

20-40

Steroid suspensions

Aggregate size

• USA DepomedrolR >50µ: 25% >1000µ: 5%

KenalogR >50µ: 25% >1000µ: 1%

Celestone SolupsanR >50µ: 25% >1000µ: 0%

• France Hydrocortancyl 125R mean 30-120µ

AltimR few small aggregates

Benzon H, Anesthesiology 2007

Tiso RL, The Spine J, 204

Roques CF, Rhumatologie 1987

Steroid suspensions

Tendancy to form particule aggregates

• USA DepomedrolR ++

KenacortR, KenalogR ++

Celestone SolupsanR +

• France Hydrocortancyl 125R ++++

AltimR + Benzon H, Anesthesiology 2007

Tiso RL, The Spine J, 204

Roques CF, Rhumatologie 1987

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

Red Blood cells agglutination

when mixed with particulate steroids: RBC agglutination

ALTIM

HYDROCORTANCYL

KENALOG

DEPOMEDROL

GROUPE SANGUIN A AB O

Pathway of the steroid to the spinal cord

1. Radiculo-medullary artery

2. Unknown arteriovenous fistula

2 février 2017 - Rupture altim -

infiltration épidurale

50

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

53

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

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infiltration épidurale

54

2 février 2017 - Rupture altim -

infiltration épidurale

55

56

57

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 2017 - Rupture altim -

infiltration épidurale

58

• addendum

Etude Study formate Biais Evaluation Results

Kennedy et al RCT

Unilateral NRP

Unilevel HD

78 pts

total

N°inj

Surgery

NS but 1.6 inj for DXM

Vs 1.4 for TC.17% DXM

vs1% TC needed 3inj

Kim & Brown 2011 RCT 30 pts

total

NS but Trend toward

less relief & shorter

duration

Park et al 2010 RCT Triamcinolone vs DXM Foraminal 106 pts

VAS TC: 8.3 2.4 at 1M

DXM: 7.4 4.1(stat si)

McGill pain,ODI: no diff

El Yagouchi 2013 Retrospective

3645 foraminal

NS

Dreyfus et al. 2006 RCT

Cervical

NS

Ahadian FM et al.

Reg Anesth Pain

Med 2011;36:572

DXM 4/8/12mg No differences

Kim et al. Clin J Pain. 2011

Sequential Triamcinolone then DXM

Delayed oral patient interview

Patient preference Inj-free interval

Higher % pts prefer TC Inj-free interval 91d/77 Disc Hern 105days/78 Foram app 89days/67

Mehta et al. PM R. 2016

Review Pain, function

NS

Shakir et al. Am J Phys Med Rehabil. 2013 Sep.

Cohort VAS NS

Lee et al. Skeletal Radiol. 2009 Nov.

Cohort VAS NS

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

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)

PEG BENZYLIC A. PARABEN BISULFITES

DEPOMEDROL

40-80 ®

Méthylprédnisolone

acétate + + - -

KENALOG® Triamcinolone acétonide - + - -

KENACORT

40-80 ®

Triamcinolone acétonide - + - -

CELESTONE

SOLUSPAN®

Bétamétasone

Sodium phosphate - - - -

DIPROSTENE® Bétamétasone

Sodium phosphate + + - -

ALTIM® Cortivazol - + - - DECADRON® Dexaméthasone sodium

phosphate - - + +

STOP

- 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)

Analyse des 12 cas:

Wybier M et al. Eur Radiol 2010

SANOFI CLINICAL TRIAL Main proposal Alternative/compl

Adult 30-55

Adult 25-50

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