SpinalSpinal CordCord StimulationStimulation forfor PHNPHN

Sang Chul Lee, MD Department of Anesthesiology & Medicin e Seoul National University Hospital PostherpeticPostherpetic neuralgia(PHN)neuralgia(PHN)

! Generally defined, pain along the course o f a nerve following the characteristic acute segmental of herpes zoster(HZ)

! Commonly used, pain persisting after the r ash has healed (usually 1 month) (variable period : 1-6months after rash on set) HerpesHerpes ZosterZoster HerpesHerpes ZosterZoster

! Varicella – predominantly a childhood disease

! Herpes Zoster () – Reactivation of a latent virus from the dorsal root or trigeminal sensory gang lion of a previously infected individual HerpesHerpes ZosterZoster

! Latent infection and reactivation – In the sensory ganglia of the spine or brainstem – by direct hematogenous seeding or ret rograde axonal spread from mucocuta neous sites – Risk of reactivation increases with age IncreasingIncreasing incidenceincidence ofof HZHZ withwith ageage

Arch Intern Med. 1995;155:1605-1609. PProgressionrogression ofof VaricellaVaricella ClinicalClinical manifestamanifesta tiontion ofof HZHZ

Clinical Management of Herpes Zoster. Amsterdam, Netherla nds: IOS Press; 1995:193-20 9. HerpesHerpes ZosterZoster

! Vesicular rash in unilateral, dermatomal di stribution, most commonly thoracic (T5-T1 2) or the ophthalmic branch of the trigemi nal nerve ! DRG, nerve root, peripheral nerve AnatomicAnatomic distributiondistribution ofof HZHZ

Region Cases(%) Thoracic 55 Cranial(trigeminal) 15 Lumbar 14 Cervical 12 Sacral 3 Disseminated 1

Herpes zoster and postherpetic neuralgia- mem enofpai Vol 1. 1990:257-63. PHNPHN

! The most common complication of zoster ! 10~70% of patients with HZ develop PHN (depending on definition) ! Rate increases with age RiskRisk factorsfactors ofof PHNPHN

! Old age ! DM ! Immune compromised pt. ! Severe skin lesion ! Prodromal symptom (pain, dysesthesia) ! Severe pain IncidenceIncidence ofof PHNPHN

! Before the introduction of antiviral drugs, t he incidence of PHN defined as ‘presence of pain’ ranges between 7–25% at three m onths and 5–13% at six months

Pain. 2007 ;128:148-56. RateRate ofof zosterzoster andand PHNPHN byby ageage

MMWR Recomm Rep. 2008 ;57:1-30 IncidenceIncidence ofof PHNPHN

Incidence at Incidence at Incidence a Age 1 month(%) 3 months(%) t 1 year(%) < 60 ye ars 8.8 2.0 0.6 > 60 ye ars 40.8 13.0 7.8

BMJ 2000;321:794-6. PainPain ofof PHNPHN

! Constant ! burning, lancinating, aching, formication (ants under the skin), dysesthesia (abnormal sensation) ! Neuropathic pain : dysaesthesia, allodynia, NeuropathicNeuropathic painpain ofof PHNPHN

! Three common component - Causalgic, dysesthetic or aching pain - Neuralgic, lancinating pain - Evoked pain(allodynia & hyperalgesia) EtiologyEtiology ofof painpain

! Viral reactivation ! Acute inflammation of dorsal root ganglio n ! Sympathetic vasoconstriction ! Irreversible neuronal damage d/t ischemia and ! Central sensitization PainPain ofof PHNPHN

!Mechanism : multiple, incompletely understood - regenerating and sprouting n. axon - central sensitization - central disinhibition CNSCNS mechanismmechanism

! Central disinhibition of A! fiber A! fiber–primary afferent neuron activate the interneuron sensitive to ischemia " Central Reorganization Deafferentation – sprouting of dorsal root to noxious receptor CentralCentral sensitizationsensitization

" “wind-up” " Increased response of dorsal horn pain-si gnaling neuron by repeated noxious stimu lation (without neuronal damage) Substan ce P, N-Methyl-D-aspartate(NMDA) PeripheralPeripheral mechanismmechanism

! Ectopic discharge -Regeneraing tips (sprouts) of damaged axo ns develop spontaneous activity and incre ased sensitivity to chemical, thermal, and mechanical stimuli -Region near the dorsal root ganglion (dista nt from the site of injury) begins to genera te “spontaneous” impulses SympathosensorySympathosensory activationactivation

! Afferent terminals or afferent somata in th e DRG acquire sensitivity to Noradrenalin by expressing _-receptors at their membra ne PostherpeticPostherpetic neuralgianeuralgia

! Resolve within 2 Mon (50%) within 1 Yr (20-30%) Pain can persist for yrs EvidenceEvidence ofof treatmenttreatment

Am Fam Physician 2005;72:1075-80 TreatmentTreatment StrategyStrategy

Topical Gabapentin, 1st line Lidocaine TCA Pregabalin patch

nd 2 /3rd line Capsaicin Valproate

TCA = tricyclic

Eur J Neurol. 2006 Nov;13(11):1153-69. 4th4th lineline Treatment?Treatment?

! Spinal cord stimulation? GoodGood RespondersResponders ofof SCSSCS

! Failed Back Syndrome ! Peripheral Vascular Disease ! CRPS I and II ! Intractable Angina ! Multiple Sclerosis ! Peripheral Neuropathy (Diabetic) PoorPoor RespondersResponders ofof SCSSCS

! Spinal Cord Trauma ! Cauda Equina Syndrome ! Post-Herpetic Neuralgia ! Perirectal Pain ! Bone / Joint Disease ! Stump/Phantom Limb Pain ! Visceral Pain GuidelineGuideline && EvidenceEvidence ofof SCSSCS EvidenceEvidence ofof SCSSCS

! Evidence suggested that SCS was effectiv e in reducing the chronic neuropathic pain of FBSS and CRPS type I.

Health Technol Assess. 2009 Mar;13(17):iii, ix-x, 1-154. EffectivenessEffectiveness ofof SCSSCS

! It is unclear how much the clinical effectiv eness of SCS in FBSS and CRPS can be g eneralised to other neuropathic pain condi tions.

Health Technol Assess 2009;13(17). IInn USAUSA

! In the United States, the primary indication s for spinal cord stimulation are failed bac k surgery syndrome and CRPS, Type I and Type II. Multiple systematic reviews, guide lines, and 3 randomized trials have been p ublished.

Pain Physician 2008; 11:393-482. EFNSEFNS guidelineguideline

! Guidelines from the European Federation of Neurological Societies (EFNS) make an evidence-based recommendation for the u se of SCS in FBSS and CRPS type I.

Eur J Pain 2007;11:2 2. EFNSEFNS guidelineguideline

! They also suggest the need for comparativ e trials in other indications, although there are reports of positive findings from case series for SCS in CRPS type II, peripheral nerve injury, , post-her petic neuralgia, amputation pain and parti al spinal cord injury.

Eur J Pain 2007;11:2 2. OutcomeOutcome ofof SCSSCS forfor PHNPHN OutcomeOutcome inin SNUH(2001-2005)SNUH(2001-2005)

Korean J Anesthesiol. 2006 Aug;51(2):195-200. OutcomeOutcome inin SNUH(2001-2005)SNUH(2001-2005)

" Response to SCS ( Excellent or Good ) • FBSS: 25.5% • PHN: 20% • CRPS: 57.1% • CBLP: 50% • Spinal cord injury: 1 person " Permanent implantation • FBSS: 43.8% • PHN: 20% • CRPS: 71.41% • CBLP: 66.7% • Spinal cord injury: 100% OutcomeOutcome inin SNUHSNUH (for(for 11yrs)11yrs)

Causes of SCS No. of patients Response to trial SCS Trial Implant Excellent Good Fair Poor PHN 32 9 11 4 3 14 FBSS 30 9 1 9 11 9 CRPS 10 6 1 5 3 1 CLBP 7 4 3 3 1 Spinal cord injury 4 1 1 2 1 Cauda equina syndrome 4 1 2 2 Brachial plexus injury 2 1 1 Etc. 10 4 6 Total 99 30 16 23 26 34

Korean J Anesthesiol. 1999 Nov;37(5):867-871. Korean J Anesthesiol. 2006 Aug;51(2):195-200. OutcomeOutcome inin SNUH(forSNUH(for 11yreas)11yreas)

! Response to SCS ( Excellent or Good ) – PHN: 46.9%

! Permanent implantation – PHN: 28.1% Etiology of Pain vs. Long-term Success Rate

Neurosurgery. 2006 Mar;58(3):481-96; discussion 481-96. Pain-relievingPain-relieving effectseffects

! Total 454 patients ! Pain relief better than 50% : carcinoma/sarcoma, causalgia ! Significantly less : PHN, thromboangitis obliterans/ASO

Anesth Analg. 1993 Jul;77(1):110-6. SCSSCS inin 6060 casescases ofof IntractableIntractable painpain

! 3 case of PHN ! 2/3 : No effect ! 1/3 : Modest benefit(33%)

J. Neurol. Neurosurg. 1991;54;196-199. SCSSCS inin thethe treatmenttreatment ofof postherpeticpostherpetic pp ainain

! Total 10 patients ! Permanent implantation: 6 patients (mean analgesia: 52.5%) ! 15 months of mean F/U all 6 patients: 74% of mean analgesia

Acta Neurochir Suppl (Wien). 1989;46:65-6. EvidenceEvidence ofof SCSSCS forfor PHNPHN

! The evidence is lacking ! Variable success rate: 20-82% ! A few Randomized Controlled Trial EvidenceEvidence ofof SCSSCS forfor PHNPHN

! In most cases, efficacy has not been adequately e xamined with controlled trials or consistently obs erved across separate investigations; some repor ts detail successful outcomes in only a single pat ient. ! With such variable findings and associated risk p otential, alternative treatments might be consider ed only for those patients whose pain is refractor y to other, better-characterized pharmacologic tre atments.

J Pain Symptom Manage. 2004 Oct;28(4):396-411. SCSSCS forfor PHNPHN

! Selection of the patient may be important

! What is the indication? IndicationIndication ofof SCSSCS

! It is known that the effect of SCS is mediat ed by large-myelinated Aß afferents, whos e collaterals ascend in the dorsal columns. ! Whereas sensory loss because of distal ax onopathy or peripheral nerve lesion is not an exclusion criterion, sparing of the dors al columns is probably necessary.

European Journal of Neurology 2007, 14: 952–970. IndicationIndication ofof SCSSCS forfor PHNPHN

! Spinal cord stimulation (SCS) may reestab lish the impaired balance between excitato ry and inhibitory mechanisms in sensitize d dorsal horn neurons as long as intraspin al neuronal death or complete deafferentat ion does not result from PHN.

Anesth Analg 2002;94:694–700. SpinalSpinal CordCord StimulationStimulation inin AcuteAcute HerpesHerpes ZosterZoster PainPain

Anesth analg 2002;94:694-700. SCSSCS forfor PHNPHN andand HZHZ painpain

! Total 32 patients (28: PHN, 4: acute HZ) ! All patient: ineffective pain medication and increasing pain ! All patients had no or little sensory loss in affected dermatomes ResultsResults

! Long term(> 2years) pain relief: 82%(23/tot al 28 patients) ! Median decrease of VAS: 9 _ 1 ! 8 patients: complete pain relief => discontinued SCS ResultsResults

! Acute HZ pain of 4 patients ! Temporary percutaneous bipolar SCS and reported immediate pain relief ! Median VAS: 9 _ 1 ! Stimulation could be terminated after medi an period of 2.5 mo because of complete p ain cessation DiscussionDiscussion

! These subjects with preserved neuronal a nd dorsal column function responded well to SCS. ! However, there are patients with marked s ensory loss in the affected dermatomes an d in constant pain without allodynia, i.e., a nesthesia dolorosa. ! To the extent that deafferentation and deg eneration of dorsal column fibers are the d ominant mechanism, patients would exper ience no change in pain with SCS DiscussionDiscussion

! SCS effects are necessarily dependent on anatomically intact pathways: the antidro mic activation of dorsal column and root fi bers may induce two dominant mechanis ms: first, a pre- and postsynaptic inhibitio n of the afferent barrage from injured perip heral neurons via GABA-ergic interneuron s ; second, suppression of sympathetic ov erdrive CaseCase 11

! F/71 ! PHN(onset: 9 yrs ago): Lt T 6,7 area ! Tightness, Shooting and lancinating pain ! Pain induced insomnia ! Medication: Morphine sulfate 50mg qid but, VAS score 10 CaseCase 11 CaseCase 11

! Percutaneous SCS trial – T8-9 Rt paraspinal approach with 15G Tuohy – Lead insertion from T3 upper border to T5 lowe r border =>stimulation:satisfactory (4-, 6+ ; 1.2V) 450pw, 40Hz ! VAS 10 _ 5 ! After 8 days, she received implantation of SCS CaseCase 11

T3

T5 CaseCase 22

! M/80 ! PHN(onset: 4yrs ago) ! Rt T 2,3 area pain ! Shooting and lancinating pain, allodynia ! No anesthesia dolorosa ! Medication: TCA, anticonvulsant but VAS 10, referred to pain clinic ! After T2, 3 nerve block & TENS, VAS 10 _ 5-6 CaseCase 22

! Percutaneous SCS trial – T5-6 Rt paraspinal approach with 15G Tuohy – Lead insertion from C7 upper border to T1 low er border at right side =>stimulation:satisfactory 2.8V, 240pw, 100Hz ! VAS 10 _ 0 ! After 10 days, he received implantation of SCS (2.1V, 70Hz, 240pw) SummarySummary

! The evidence of SCS for PHN is low grade ! More randomized controlled trial is necess ary ! Can not control the pain by medication ! Risk vs. Benefit ! If you select the careful indication (preserv ed neuronal & dorsal column function), SC S may be effective. ThankThank you!you!