Facial PainFacial Pain

Steven J. ScrivaniSteven J. ScrivaniProfessorProfessor

The Craniofacial Pain and Headache CenterThe Craniofacial Pain and Headache CenterOral/Maxillofacial SurgeryOral/Maxillofacial Surgery

Tufts University School of Dental MedicineTufts University School of Dental Medicine

Department of Public Health and Family MedicineDepartment of Public Health and Family MedicinePublic Health and Professional Degree ProgramsPublic Health and Professional Degree Programs

Pain Research, Education and Policy Pain Research, Education and Policy Tufts University School of MedicineTufts University School of Medicine

Research AssociateResearch AssociatePain and Analgesia Imaging and Neuroscience (P.A.I.N.) GroupPain and Analgesia Imaging and Neuroscience (P.A.I.N.) Group

Brain Imaging CenterBrain Imaging CenterMcLean HospitalMcLean Hospital

Harvard Medical SchoolHarvard Medical School

DisclosuresDisclosures

Funding from:Funding from:

1.1. NIHNIH

2.2. GlaxoSmithKlineGlaxoSmithKline

3.3. Merck and Co., Inc.Merck and Co., Inc.

4.4. Endo Pharmaceuticals, Inc.Endo Pharmaceuticals, Inc.

International Headache SocietyInternational Headache SocietyInternational Classification of Headache Disorders II International Classification of Headache Disorders II

(ICHD II)(ICHD II)CephalalgiaCephalalgia, 2004, 2004

14 CATEGORIES14 CATEGORIES

•• The primary headaches: 1The primary headaches: 1--44

•• The secondary headaches: 5The secondary headaches: 5--1212

•• Cranial neuralgias, central and primary facial pain Cranial neuralgias, central and primary facial pain and other headache disorders: 13and other headache disorders: 13

•• Others: 14Others: 14

““224 Diagnoses224 Diagnoses””

Headache or facial pain attributed to disorders of Headache or facial pain attributed to disorders of cranium, neck, eyes, ears, nose, sinuses, teeth, mouth or cranium, neck, eyes, ears, nose, sinuses, teeth, mouth or

other facial or cranial structures (11.1other facial or cranial structures (11.1--8)8)

11.1 11.1 –– Cranial bonesCranial bones

11.2 11.2 –– NeckNeckCervicogenic headacheCervicogenic headache

11.3 11.3 –– EyesEyes

11.4 11.4 –– EarsEars

11.5 11.5 –– Sinus disorders (Sinus disorders (““Sinus headacheSinus headache””))

11.6 11.6 –– Teeth, jaws or related structuresTeeth, jaws or related structures

11.7 11.7 –– TMJ disorders (TMD) TMJ disorders (TMD)

Cranial neuralgias, central and primary facial Cranial neuralgias, central and primary facial pain and other headaches (13.1pain and other headaches (13.1--19)19)

13.1 13.1 –– Trigeminal neuralgiaTrigeminal neuralgia13.2 13.2 –– GlossopharyngealGlossopharyngeal neuralgianeuralgia13.3 13.3 –– NervusNervus intermediusintermedius neuralgianeuralgia

13.4 13.4 –– Superior laryngeal neuralgiaSuperior laryngeal neuralgia

13.5 13.5 –– NasociliaryNasociliary neuralgianeuralgia

13.6 13.6 –– SupraorbitalSupraorbital neuralgianeuralgia

13.7 13.7 –– Other terminal branch neuralgiasOther terminal branch neuralgias

13.8 13.8 –– Occipital neuralgiaOccipital neuralgia

13.9 13.9 –– NeckNeck--tongue syndrometongue syndrome13.12 13.12 –– Constant pain caused by compression, irritation Constant pain caused by compression, irritation

or distortion of cranial nerves or upper cervical roots or distortion of cranial nerves or upper cervical roots by by structural lesionsstructural lesions

13.15 13.15 –– Head or facial pain attributed to herpes zoster Head or facial pain attributed to herpes zoster postpost--herpetic neuralgiaherpetic neuralgia

13.16 13.16 –– TolosaTolosa--Hunt syndromeHunt syndrome13.18 13.18 –– Central causes of facial pain Central causes of facial pain

anesthesia dolorosaanesthesia dolorosacentral postcentral post--stroke painstroke painfacial pain attributed to multiple sclerosisfacial pain attributed to multiple sclerosispersistent idiopathic facial painpersistent idiopathic facial painburning mouth syndromeburning mouth syndrome

Oral and Maxillofacial ConditionsOral and Maxillofacial Conditions•• Dentoalveolar PathologyDentoalveolar Pathology

*pulpal*pulpal*periodontal*periodontal

•• Odontogenic and NonOdontogenic and Non--odontogenic Pathology odontogenic Pathology •• Temporomandibular DisordersTemporomandibular Disorders•• Oral Mucous Membrane DiseaseOral Mucous Membrane Disease•• Oral Manifestations of Systemic DiseaseOral Manifestations of Systemic Disease•• Neuropathic Pain (Persistent Idiopathic Facial Pain)Neuropathic Pain (Persistent Idiopathic Facial Pain)•• Trigeminal NeuralgiaTrigeminal Neuralgia•• PostherpeticPostherpetic NeuralgiaNeuralgia““Burning Mouth/Tongue DisorderBurning Mouth/Tongue Disorder””

TRIGEMINAL NEURALGIATRIGEMINAL NEURALGIA““Trigeminal Neuralgia EquivalentsTrigeminal Neuralgia Equivalents””

(Modified W.H. Sweet criteria)(Modified W.H. Sweet criteria)

1. Paroxysmal, severe, 1. Paroxysmal, severe, lancinatinglancinating painpain2. Trigger areas2. Trigger areas3. Unilateral3. Unilateral4. No sensory deficit4. No sensory deficit5. Restricted to the distribution of the 5. Restricted to the distribution of the

trigeminal nervetrigeminal nerve6. No obvious source of pathology 6. No obvious source of pathology

Trigeminal Neuralgia IsTrigeminal Neuralgia Is……•• Not very common (5 per 100,000 population Not very common (5 per 100,000 population

annually).annually).•• Typically in persons around age 60.Typically in persons around age 60.•• More often in women.More often in women.•• More often on the right side of the face.More often on the right side of the face.•• More often in the region around the mouth and jaws.More often in the region around the mouth and jaws.

CHARACTERISTICS OF PATIENTSCHARACTERISTICS OF PATIENTSMathews ES, Scrivani SJ: Mount Sinai Journal of Medicine. 67:28Mathews ES, Scrivani SJ: Mount Sinai Journal of Medicine. 67:2888--299, 2000.299, 2000.

SCRIVANISCRIVANI ****COMBINEDCOMBINEDAVERAGE AGE 61.5 AVERAGE AGE 61.5 6565

(RA(RANGE:41NGE:41--95) 95) SEX 69%FEMSEX 69%FEMALE ALE

62%FEMALE62%FEMALESIDE OF FACE 58%RIGHT SIDE OF FACE 58%RIGHT 60%RIGHT60%RIGHTDIVISION INVOLVED:DIVISION INVOLVED:

•• VV--1 0 1 0 1%1%

•• VV--2 13% 2 13% 16%16%

•• VV--3 38% 3 38% 15%15%

•• VV--1, V1, V--2 8% 2 8% 15%15%

CLASSIFICATION OF TNCLASSIFICATION OF TN

•• ““ClassicalClassical”” or Primary TN or Primary TN –– IdiopathicIdiopathic

•• ““SymptomaticSymptomatic”” or Secondary TN or Secondary TN ––Associated with another disease processAssociated with another disease process

•• PrePre--trigeminal neuralgiatrigeminal neuralgia•• Atypical TNAtypical TN

DiagnosisDiagnosis HistoryHistory

Trigeminal neuralgia Type 1Trigeminal neuralgia Type 1

Spontaneous onsetSpontaneous onset

> 50% episodic pain> 50% episodic pain

Trigeminal neuralgia Type 2Trigeminal neuralgia Type 2 > 50% constant pain> 50% constant pain

Trigeminal injuryTrigeminal injury

Trigeminal Trigeminal neuropathicneuropathic painpain Unintentional, incidental traumaUnintentional, incidental trauma

Trigeminal Trigeminal deafferentationdeafferentation painpain Intentional Intentional deafferentationdeafferentation

Symptomatic trigeminal neuralgiaSymptomatic trigeminal neuralgia Multiple sclerosisMultiple sclerosis

PostherpeticPostherpetic neuralgianeuralgia Trigeminal Herpes zoster Trigeminal Herpes zoster outbreakoutbreak

Atypical facial pain *Atypical facial pain * Somatoform pain disorderSomatoform pain disorder

* Cannot be diagnosed by history * Cannot be diagnosed by history alonealone

BurchielBurchiel K: Neurosurgery, 2003.K: Neurosurgery, 2003.

Structural Lesions and Facial PainStructural Lesions and Facial Pain

•• MS PlaquesMS Plaques

•• CP Angle TumorsCP Angle Tumors

•• SchwannomasSchwannomas

•• ChiariChiari MalformationsMalformations

•• Midbrain LesionsMidbrain Lesions

•• Pontine HemorrhagePontine Hemorrhage

•• Skull Base TumorsSkull Base Tumors

•• SC CarcinomasSC Carcinomas

•• Salivary Gland TumorsSalivary Gland Tumors

•• Oral Cancers (SCC)Oral Cancers (SCC)

•• Vascular MalformationsVascular Malformations

•• Carotid/Vertebral Carotid/Vertebral DiseaseDisease

Facial Pain and Cerebellopontine Angle Facial Pain and Cerebellopontine Angle TumorsTumors

Nguyen M, Nguyen M, MaciewiczMaciewicz R, et al: R, et al: ClinClin J Pain, 1986.J Pain, 1986.

1.1. MeningiomasMeningiomas: variable pattern of cranial : variable pattern of cranial nerve V, VII, VIII deficitsnerve V, VII, VIII deficits

2.2. Acoustic Acoustic neuromasneuromas: cranial nerve VII : cranial nerve VII deficitsdeficits

3.3. EpidermoidEpidermoid tumors: few signs or tumors: few signs or symptoms other than facial painsymptoms other than facial pain

Comprehensive Study of Diagnosis and Treatment of Comprehensive Study of Diagnosis and Treatment of Trigeminal Neuralgia Secondary to Tumors Trigeminal Neuralgia Secondary to Tumors

Cheng TM, Cheng TM, CascinoCascino TL, TL, OnofrioOnofrio BM: Neurology, 1993. BM: Neurology, 1993.

19761976--1990: 5,058 patients1990: 5,058 patients

TN= 2,972TN= 2,972

•• Tumors in 296/2,972 (9.95%)Tumors in 296/2,972 (9.95%)>>MeningiomaMeningioma

>>SchwannomaSchwannoma

>Pituitary tumors>Pituitary tumors

>Others: >Others: gliomaglioma, lymphoma, , lymphoma, arachnoidarachnoid cyst, cyst, SCCSCC

•• 47% developed neurological deficits (avg. 6.3 yrs)47% developed neurological deficits (avg. 6.3 yrs)

Chronic Chronic NeurogenicNeurogenic Facial Pain & Facial Pain & TumorsTumors

Scrivani SJ, Scrivani SJ, MaciewiczMaciewicz RJ, Keith DA, Mathews ES: 1997.RJ, Keith DA, Mathews ES: 1997.

19921992--19961996

575 patients with chronic neurogenic 575 patients with chronic neurogenic facial painfacial pain

360 (63%) 360 (63%) -- initial diagnosis of TNinitial diagnosis of TN

8.4% had structural pathology on MRI8.4% had structural pathology on MRI(Unpublished)(Unpublished)

MSMS

ETIOLOGY ??ETIOLOGY ??

*Peripheral vs. Central ??*Peripheral vs. Central ??

*Chronic irritation / inflammation ??*Chronic irritation / inflammation ??

*Ectopic afferent activity ??*Ectopic afferent activity ??

**DemyelinationDemyelination ????

*Seizure activity / epilepsy ??*Seizure activity / epilepsy ??

*Vascular compression ??*Vascular compression ??

Diagnostic EvaluationDiagnostic Evaluation

FACIAL PAINFACIAL PAIN

1.1. ParoxysmalParoxysmal2.2. Trigger ZonesTrigger Zones3.3. UnilateralUnilateral4.4. Restricted to Area ofRestricted to Area of

Trigeminal NerveTrigeminal Nerve5.5. No Sensory DeficitNo Sensory Deficit

NoNo Further Evaluation byFurther Evaluation byInterInter--disciplinarydisciplinaryCraniofacial Pain Center Craniofacial Pain Center

YesYes

MRI NormalMRI Normal NoNo

LesionLesion

DemyelinatingDemyelinatingPlaquesPlaques

Vascular AbnormalityVascular Abnormality

NeurologyNeurologyNeurosurgeryNeurosurgeryConsultConsult

NeurologyNeurologyConsultConsult

Imaging+Imaging+NeurosurgeryNeurosurgeryConsultConsult

Diagnostic EvaluationDiagnostic EvaluationHistory History Physical Examination Physical Examination –– neurological testingneurological testingBrain Imaging Brain Imaging –– MRI/MRAMRI/MRAFurther Diagnostic Studies??Further Diagnostic Studies??

Neuropathic Pain Scale Base Rate for Neuropathic Pain Scale Base Rate for Orofacial Pain PopulationOrofacial Pain PopulationSteven J. Scrivani, Ronald J. Kulich, Steven J. Scrivani, Ronald J. Kulich, NaifNaif BindayelBindayel, , BrijeshBrijesh ChandwaniChandwani, , NoshirNoshir Mehta: Mehta: 2006.2006.

•• 145 patients 145 patients •• Unpleasant and intense neuropathic pain Unpleasant and intense neuropathic pain

characteristics had the two highest score (4.58 characteristics had the two highest score (4.58 and 4.35 respectively). and 4.35 respectively).

•• Cold and itchy items of the NPS presented the Cold and itchy items of the NPS presented the lowest means (0.70 and 0.44 respectively). lowest means (0.70 and 0.44 respectively).

•• The findings were found to match other The findings were found to match other neuropathic pain groups (peripheral neuropathic pain groups (peripheral neuropathic pain, diabetic neuropathic). neuropathic pain, diabetic neuropathic).

Biomarkers and TNBiomarkers and TNBouckomsBouckoms AJ, Sweet WH, AJ, Sweet WH, PolettiPoletti C, C, LavoriLavori P, Carr D, Matson W, P, Carr D, Matson W, GamacheGamache P, P, AroninAronin N: Monoamines in the N: Monoamines in the

brain cerebrospinal fluid of facial pain patients. Anesthesia Prbrain cerebrospinal fluid of facial pain patients. Anesthesia Progress. 39(6):201ogress. 39(6):201--8, 1992.8, 1992.BouckomsBouckoms AJ, AJ, PolettiPoletti CH, Sweet WH, Carr D, Keith DA: Trigeminal facial pain: a modelCH, Sweet WH, Carr D, Keith DA: Trigeminal facial pain: a model of peptides and of peptides and

monoamines in monoamines in intracerebralintracerebral cerobrospinalcerobrospinal fluid. fluid. AgressologieAgressologie. 32:27. 32:27--274, 1991.274, 1991.

•• Assay monoamines in cerebrospinal fluid (CSF) obtained Assay monoamines in cerebrospinal fluid (CSF) obtained from the trigeminal cistern of 64 patients with from the trigeminal cistern of 64 patients with intractable facial pain. intractable facial pain.

•• The CSF was analyzed for endThe CSF was analyzed for end--product markers of product markers of activity for the dopamine, serotonin, and activity for the dopamine, serotonin, and norepinephrinenorepinephrine systems, respectively. systems, respectively.

•• Brain CSF monoamine metabolites reflect a different Brain CSF monoamine metabolites reflect a different profile of profile of dopaminergicdopaminergic and and serotonergicserotonergic functioning in functioning in these facial pain patients from that previously reported these facial pain patients from that previously reported with lumbar CSF measurements of normal patients.with lumbar CSF measurements of normal patients.

•• The The serotonergicserotonergic system is hypoactive as judged by low system is hypoactive as judged by low 55--hydroxyindoleacetic acid (5hydroxyindoleacetic acid (5--HIA). HIA).

Salivary BiomarkersSalivary Biomarkers

Substance PSubstance P

CalcitoninCalcitonin Gene Related Peptide (CGRP)Gene Related Peptide (CGRP)

CortisolCortisol

ProstaglandinsProstaglandins

SerotoninSerotonin

Functional Brain ImagingFunctional Brain Imaging

Functional Magnetic Resonance Imaging (fMRI)Functional Magnetic Resonance Imaging (fMRI)

Ganglion Spinal Nucleus CortexThalamus

V1DM

VPM

V31

23

Imaging the Pain Pathway: Imaging the Pain Pathway: Trigeminal SystemTrigeminal System

Borsook et al., J Neuroscience, 2004.Borsook et al., J Neuroscience, 2004.

Trigeminal NeuralgiaTrigeminal NeuralgiaBorsookBorsook, Scrivani, Becerra, et al: Molecular Pain, 2007., Scrivani, Becerra, et al: Molecular Pain, 2007.

0

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Trigeminal Neuropathic PainTrigeminal Neuropathic PainBecerra, Scrivani, Keith, Becerra, Scrivani, Keith, BorsookBorsook, et al: J Neuroscience, 2006., et al: J Neuroscience, 2006.

Becerra et al. J Neuroscience, 2006.Becerra et al. J Neuroscience, 2006.Brush Cold Heat

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RecruitSubjects

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fMRI – 1 fMRI - 2

50% Drug Taper Placebo Taper

fMRI – 1 fMRI - 2

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VAS Scores: Heat Affected

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Trigeminal Neuropathy: Trigeminal Neuropathy: LamotrigineLamotrigine StudyStudyScrivani, Scrivani, BorsookBorsook, Keith, et al. Pain Medicine, 2010., Keith, et al. Pain Medicine, 2010.

Trigeminal NeuralgiaTrigeminal NeuralgiaTherapeutic OptionsTherapeutic Options

The disorders you can The disorders you can ““FF…”…”FFerment,erment,FFascinate, ascinate, FFry,ry,FFreeze,reeze,FFondle,ondle,FFibrillate,ibrillate,FFreeree--radical,radical,

However, not However, not ““ffigure outigure out””

CURRENT TREATMENT CURRENT TREATMENT STRATEGIESSTRATEGIES

MEDICAL MANAGEMENTMEDICAL MANAGEMENT*Pharmacologic*Pharmacologic*Non*Non--pharmacologicpharmacologic

SURGICAL MANAGEMENTSURGICAL MANAGEMENT*Peripheral*Peripheral*Intra*Intra--cranialcranial

Scrivani, Mathews, Scrivani, Mathews, MaciewiczMaciewicz: Oral : Oral SurgSurg Oral Med Oral Path, 2007.Oral Med Oral Path, 2007.

Anticonvulsants (Anticonvulsants (AEDsAEDs))

•• PhenytoinPhenytoin ((DilantinDilantin))

•• CarbamazepineCarbamazepine ((TegretolTegretol))

•• ValproicValproic acid (acid (DepakoteDepakote))

•• BaclofenBaclofen ((LioresalLioresal))

•• ClonazepamClonazepam ((KlonopinKlonopin))

•• GabapentinGabapentin ((NeurontinNeurontin))

•• LamotrigineLamotrigine ((LamictalLamictal))

•• TopiramateTopiramate ((TopamaxTopamax))•• OxcarbazepineOxcarbazepine ((TrileptalTrileptal))•• TiagabineTiagabine ((GabatrilGabatril))•• LevetiracetamLevetiracetam ((KeppraKeppra))•• ZonisamideZonisamide ((ZonegranZonegran))•• PregabalinPregabalin ((LyricaLyrica))

Lidocaine Lidocaine MexilitineMexilitine ((MexitilMexitil))

Anticonvulsants and Neuropathic PainAnticonvulsants and Neuropathic Pain

•• Trigeminal Neuralgia Trigeminal Neuralgia

•• PostPost--herpetic Neuralgiaherpetic Neuralgia

•• Peripheral Diabetic Neuropathy/NeuralgiaPeripheral Diabetic Neuropathy/Neuralgia

•• HIV Neuropathy/NeuralgiaHIV Neuropathy/Neuralgia

•• Central Pain StatesCentral Pain States

•• MigraineMigraine

Anticonvulsants and Neuropathic PainAnticonvulsants and Neuropathic PainMcQuayMcQuay, Carroll, , Carroll, JadadJadad, , WiffenWiffen, Moore: BMJ. 311:1047, Moore: BMJ. 311:1047--1052, 1995.1052, 1995.

•• MetaMeta--analysis analysis –– randomized controlled trials randomized controlled trials (1966(1966--1994)1994)

•• 37 identified, 20 met selection criteria37 identified, 20 met selection criteria

•• 1 placebo1 placebo--controlled study for acute paincontrolled study for acute pain

•• TN TN –– 56% vs. 18%56% vs. 18%

•• PDN PDN –– 82% vs. 43%82% vs. 43%

•• Migraine Migraine –– 85% vs. 22%85% vs. 22%

Anticonvulsants and Acute and Anticonvulsants and Acute and Chronic PainChronic Pain

Cochrane Collaboration, Cochrane Pain, Palliative and SupportiveCochrane Collaboration, Cochrane Pain, Palliative and Supportive Care. 3, Care. 3, Feb. 23, 2000.Feb. 23, 2000.

•• Randomized controlled trials (1966Randomized controlled trials (1966--1999)1999)

•• 23 trial of 6 anticonvulsant drugs (1,074 23 trial of 6 anticonvulsant drugs (1,074 patients)patients)

•• Anticonvulsants more effective than placeboAnticonvulsants more effective than placebo

•• GabapentinGabapentin not superior to not superior to carbamazepinecarbamazepine

•• No trials compared different anticonvulsantsNo trials compared different anticonvulsants

RCTsRCTs and and AEDsAEDs for TNfor TN

•• BaclofenBaclofen –– Fromm, Terrence, Fromm, Terrence, ChatthaChattha, 1984; , 1984; Fromm, Terrence, 1987.Fromm, Terrence, 1987.

•• CarbamazepineCarbamazepine –– Campbell, et al, 1966; Campbell, et al, 1966; Killian, Fromm, 1968; Killian, Fromm, 1968; NicolNicol, 1969., 1969.

•• TizanidineTizanidine (vs. CBZ) (vs. CBZ) –– VilmingVilming, et al, 1986., et al, 1986.•• LamotrigineLamotrigine –– ZakrzewskaZakrzewska, et al, 1997., et al, 1997.•• TopiramateTopiramate –– GilronGilron, et al, 2001., et al, 2001.

AEDsAEDs for TN for TN –– Open Label & Case Open Label & Case ReportsReports

••ValproicValproic acid acid

••ClonazepamClonazepam

••GabapentinGabapentin

••LamotrigineLamotrigine

••OxcarbazepineOxcarbazepine

••PregabalinPregabalin

Pharmacological Therapy for Pharmacological Therapy for Trigeminal NeuralgiaTrigeminal Neuralgia

Mathews ES, Scrivani SJ: Mount Sinai Journal of Medicine. 67:288Mathews ES, Scrivani SJ: Mount Sinai Journal of Medicine. 67:288--299, 2000.299, 2000.

61% of patients with TN61% of patients with TN54 patients prospectively followed:54 patients prospectively followed:

•• Excellent pain control (no pain)Excellent pain control (no pain) 27(50%)27(50%)

•• Good pain control (satisfactory)Good pain control (satisfactory) 19 (35%)19 (35%)

•• Fair/Poor pain control (unsatisfactory)Fair/Poor pain control (unsatisfactory) 8 (15%)8 (15%)

Pharmacological TherapyPharmacological TherapyScrivani SJ, Mathews ES, Scrivani SJ, Mathews ES, RabinovichRabinovich A: AAOP, 2004.A: AAOP, 2004.

152 patients 152 patients –– retrospective surveyretrospective survey•• GabapentinGabapentin ((NeurontinNeurontin) = 39.3%) = 39.3%•• CarbamazepineCarbamazepine ((TegretolTegretol) = 60.0%*) = 60.0%*•• GabapentinGabapentin + other = 78%+ other = 78%•• CarbamazepineCarbamazepine + other = 70%+ other = 70%•• Other Other AEDsAEDs –– baclofenbaclofen, , clonazepamclonazepam, , topiramatetopiramate, etc. , etc. •• Side effects Side effects –– N = 12%**N = 12%**

TegTeg = 31%= 31%

Negative outcome coNegative outcome co--factors factors –– duration & tactile triggersduration & tactile triggers

EvidenceEvidence--based approach to the medical based approach to the medical management of trigeminal neuralgia.management of trigeminal neuralgia.

JornsJorns TP, TP, ZakrzewskaZakrzewska JM: Br J JM: Br J NeurosurgNeurosurg. 21:253. 21:253--261, 2007.261, 2007.

•• 4 systematic reviews, of which one was a meta4 systematic reviews, of which one was a meta--analysis analysis and 18 randomized controlled trials (RCT) on and 18 randomized controlled trials (RCT) on medical management of trigeminal neuralgia. medical management of trigeminal neuralgia.

•• The evidence suggests that The evidence suggests that carbamazepinecarbamazepine is still the is still the first line drug for medical management, but this first line drug for medical management, but this should be changed to should be changed to oxcarbazepineoxcarbazepine if there is poor if there is poor efficacy and an unacceptable side effect profile. efficacy and an unacceptable side effect profile.

•• Combination of Combination of carbamazepinecarbamazepine with with lamotriginelamotrigine or or baclofenbaclofen is the second line treatment when is the second line treatment when monotherapymonotherapy fails, but the evidence is weak. fails, but the evidence is weak.

TOPICAL AGENTSTOPICAL AGENTS

•• NSAIDsNSAIDs ((DiclofenacDiclofenac gel & patch=gel & patch=FlectorFlector))

•• Opioids (Opioids (TransdermalTransdermal & & transmucosaltransmucosal fentanylfentanyl))

•• Local anesthetics (Local anesthetics (LidocaineLidocaine==LidodermLidoderm))

•• CorticosteroidsCorticosteroids

•• Anticonvulsants (Anticonvulsants (AEDsAEDs))

•• CapsaisinCapsaisin ((ZostrixZostrix & & QutenzaQutenza))

•• ClonidineClonidine

•• KetamineKetamine **CannabinoidsCannabinoids????•• Cold/IceCold/Ice

Treatment of Acute AttacksTreatment of Acute Attacks

••Trigeminal nerve blockadeTrigeminal nerve blockadeLocal AnesthesiaLocal Anesthesia

BotulinumBotulinum toxin??toxin??

••Intravenous therapyIntravenous therapy

LidocaineLidocaine

FosphenytoinFosphenytoin ((CerebyxCerebyx))

ValproicValproic acid (acid (DepaconDepacon))

SURGICAL INTERVENTIONSSURGICAL INTERVENTIONS

••Peripheral ProceduresPeripheral Procedures

••Intracranial ProceduresIntracranial Procedures

PERIPHERAL PROCEDURESPERIPHERAL PROCEDURES

••INJECTIONINJECTIONAlcoholAlcohol

GlycerolGlycerol

Local anesthetic +/Local anesthetic +/-- steroidsteroid

Streptomycin +/Streptomycin +/-- local anestheticlocal anesthetic

Retrograde Retrograde adriamycinadriamycinganglionectomyganglionectomy

••SURGICALSURGICALNerve decompressionNerve decompression

NeurectomyNeurectomy

ElectrocauteryElectrocautery

CryotherapyCryotherapy

Bone curettageBone curettage

LOCAL ANESTHETIC NERVE LOCAL ANESTHETIC NERVE BLOCK INJECTIONSBLOCK INJECTIONS

Botulinum Toxin??Botulinum Toxin??

INTRACRANIAL PROCEDURESINTRACRANIAL PROCEDURES•• INJECTIONINJECTION

**RetrogasserianRetrogasserian Lidocaine InjectionLidocaine Injection*Glycerol or Phenol *Glycerol or Phenol GangliolysisGangliolysis

•• SURGICALSURGICAL**PercutaneousPercutaneous Stereotactic Radiofrequency ThermalStereotactic Radiofrequency Thermal

RhizotomyRhizotomy*PFE/MVD*PFE/MVD*Gamma Knife *Gamma Knife Radiosurgery/CyberknifeRadiosurgery/Cyberknife RadiosurgeryRadiosurgery**GasserianGasserian Balloon Balloon GanglionotomyGanglionotomy*Partial Sensory *Partial Sensory RhizotomyRhizotomy*DREZ Lesion*DREZ Lesion*Nucleus *Nucleus CaudalisCaudalis TractotomyTractotomy ((CordotomyCordotomy))**GasserianGasserian Ganglion Chronic Electrical Ganglion Chronic Electrical

NeurostimulationNeurostimulation*Brain Stimulation (Motor Cortex)*Brain Stimulation (Motor Cortex)

COMPARISON OF DIFFERENT PROCEDURES IN THE COMPARISON OF DIFFERENT PROCEDURES IN THE TREATMENT OF TRIGEMINAL NEURALGIATREATMENT OF TRIGEMINAL NEURALGIA

Technique Technique ImmedImmed Recurrence Recurrence DysesthesiaDysesthesia AnesthAnesth Weakness Weakness MorbMorb MortMortrelief (%)relief (%) dolorosadolorosa

______________________________________________________________________________________________________________________________________________________

MVDMVD 95(70) 1795(70) 17--25 0.525 0.5 0.10.1 0.10.1 1010 0.60.6

GKRGKR 80(54) 580(54) 5--30? 12(25) 3(12) 0 10 030? 12(25) 3(12) 0 10 0

RTRRTR 95(91) 23 95(91) 23 1010 1.51.5 2424 1.21.2 00

*RTR*RTR 87(83) 2787(83) 27 8.48.4 1.81.8 2929 1.81.8 0 0

*Scrivani, et al: J Oral and *Scrivani, et al: J Oral and MaxillofacMaxillofac SurgSurg, 1999., 1999.* Mathews, Scrivani: Mt Sinai J Med, 2000.* Mathews, Scrivani: Mt Sinai J Med, 2000.

Radiofrequency Thermal Radiofrequency Thermal RhizotomyRhizotomySweet WH, Sweet WH, WepsicWepsic JG: Controlled JG: Controlled thermocoagulationthermocoagulation of trigeminal ganglion and of trigeminal ganglion and

rootlets for differential destruction of pain fibers: trigeminalrootlets for differential destruction of pain fibers: trigeminal neuralgia, J neuralgia, J NeurosurgNeurosurg. . 39:14339:143--156, 1974.156, 1974.

•• 274 patients with facial pain274 patients with facial pain

•• 214 with TN214 with TN

•• 154 patients treated with RTR154 patients treated with RTR

•• 140/154 (91%) 140/154 (91%) –– complete pain reliefcomplete pain relief

•• 25/154 (16%) 25/154 (16%) –– inadequate pain relief or pain inadequate pain relief or pain recurred within daysrecurred within days

•• 16/25 (64%) 16/25 (64%) –– repeat procedure and pain reliefrepeat procedure and pain relief

•• LongLong--term followterm follow--up up –– 125 patients followed for 125 patients followed for

2 2 ½½ to 6 years, the late recurrence rate was 22%to 6 years, the late recurrence rate was 22%

A prospective 15A prospective 15--year follow up of 154 patients with year follow up of 154 patients with trigeminal neuralgia treated by trigeminal neuralgia treated by percutaneouspercutaneous

stereotactic radiofrequency stereotactic radiofrequency rhizotomyrhizotomyTahaTaha and and TewTew: J : J NeurosurgNeurosurg. 83:989, 1995. 83:989, 1995

*Initial pain relief *Initial pain relief -- 99%99%

*Recurrence requiring reoperation *Recurrence requiring reoperation -- 23 (15%)23 (15%)

*Recurrence not requiring reoperation *Recurrence not requiring reoperation -- 10 (6%)10 (6%)

**DysesthesiaDysesthesia -- 31 (23%)31 (23%)

*Median pain free *Median pain free -- 32 mo. for mild 32 mo. for mild hypoalgesiahypoalgesia

15 yrs. for dense 15 yrs. for dense hypoalgesiahypoalgesia/analgesia/analgesia

**15 years after 1 or 2 PSR = 95% rated the procedure **15 years after 1 or 2 PSR = 95% rated the procedure excellent or good excellent or good

Mathews ES, Scrivani SJ: The Mount Sinai Journal of Medicine, 20Mathews ES, Scrivani SJ: The Mount Sinai Journal of Medicine, 200000

****258 PATIENTS (1991258 PATIENTS (1991--1997)1997)Early pain relief (0Early pain relief (0--6 months):6 months):•• Excellent or good (successful)Excellent or good (successful) 224/258 (87%)224/258 (87%)•• Fair (unsuccessful)Fair (unsuccessful) 21/258 (8%)21/258 (8%)•• Poor (failures)Poor (failures) 13/258 (5%)13/258 (5%)

•• Recurrences(reRecurrences(re--operation) operation) 24 (11%) 24 (11%) •• Recurrences(no reRecurrences(no re--operation) operation) 35 (16%)35 (16%)

Long term overall pain relief (12 mo.Long term overall pain relief (12 mo.--80 mo.) (83%)80 mo.) (83%)Mean = 40 monthsMean = 40 months

Systematic review of ablative neurosurgical techniques Systematic review of ablative neurosurgical techniques for the treatment of trigeminal neuralgiafor the treatment of trigeminal neuralgia

Lopez BC. Hamlyn PJ. Lopez BC. Hamlyn PJ. ZakrzewskaZakrzewska JM. Neurosurgery. 54(4):973JM. Neurosurgery. 54(4):973--82; discussion 98282; discussion 982--3, 2004.3, 2004.

•• Of 175 studies identified, 9 could be used to evaluate Of 175 studies identified, 9 could be used to evaluate rates of complete pain relief on a yearly basis and 22 rates of complete pain relief on a yearly basis and 22 could be used to evaluate complications. could be used to evaluate complications.

•• Radiofrequency Radiofrequency thermocoagulationthermocoagulation offered higher offered higher rates of complete pain relief, compared with glycerol rates of complete pain relief, compared with glycerol rhizolysisrhizolysis and stereotactic and stereotactic radiosurgeryradiosurgery, although it , although it demonstrated the demonstrated the greatest number of complications. greatest number of complications.

•• There are presently insufficient goodThere are presently insufficient good--quality data on quality data on percutaneouspercutaneous BC for evaluation of its results, in BC for evaluation of its results, in comparison with the other techniques. comparison with the other techniques.

The LongThe Long--Term Outcome of Term Outcome of MicrovascularMicrovascularDecompression for Trigeminal NeuralgiaDecompression for Trigeminal Neuralgia

Barker FG, Barker FG, JannettaJannetta PJ, et al: NEJM, 1996PJ, et al: NEJM, 1996

•• 1185 patients, 201185 patients, 20--year followyear follow--upupImmediate Immediate postoppostop relief= 82%relief= 82%Partial relief= 16%Partial relief= 16%No relief= 2%No relief= 2%

•• 30% Recurrence, mean 6.2 yrs.30% Recurrence, mean 6.2 yrs.•• 10 years: 70% pain free, no meds10 years: 70% pain free, no meds•• Complications: 2 deaths, 1 brainstem infarct Complications: 2 deaths, 1 brainstem infarct

and 16 hearing loss (1.4%)and 16 hearing loss (1.4%)

Predictors of Outcome in Surgically Managed Patients with Predictors of Outcome in Surgically Managed Patients with Typical and Atypical Trigeminal Neuralgia: Comparison of Typical and Atypical Trigeminal Neuralgia: Comparison of

Results Following Results Following MicrovascularMicrovascular DecompressionDecompressionTylerTyler--KabaraKabara EC, EC, KassamKassam AB, Horowitz MH, AB, Horowitz MH, UrgoUrgo L, Levy EI, L, Levy EI, CahngCahng YF: J YF: J NeurosurgNeurosurg 96:52796:527--531, 2002.531, 2002.

•• 2003 TN2003 TN•• Complete postoperative pain relief: 80%Complete postoperative pain relief: 80%•• LongLong--term pain relief (> 5 yrs.):term pain relief (> 5 yrs.):

TN TN –– 73% excellent, 7% good = 80%73% excellent, 7% good = 80%•• Recent onset was a predictors of better postoperative Recent onset was a predictors of better postoperative

pain reliefpain relief•• Preoperative sensory loss was a negative predictor for Preoperative sensory loss was a negative predictor for

satisfactory longsatisfactory long--term pain reliefterm pain relief

MicrovascularMicrovascular decompression for primary trigeminal neuralgia: longdecompression for primary trigeminal neuralgia: long--term term effectiveness and prognostic factors in a series of 362 consecuteffectiveness and prognostic factors in a series of 362 consecutive patients ive patients

with clearwith clear--cut neurovascular conflicts who underwent pure cut neurovascular conflicts who underwent pure decompression.decompression.

SindouSindou M, M, LestonLeston J, J, DecullierDecullier E, E, ChapuisChapuis F: J F: J NeurosurgNeurosurg. 107: 1144. 107: 1144--1153, 2007.1153, 2007.

•• PainPain--free without any medication was 91% at 1 year free without any medication was 91% at 1 year

•• Estimated to be 73.38% after 15 years of followEstimated to be 73.38% after 15 years of follow--up.up.

•• Involvement of all three divisions of the nerve had a Involvement of all three divisions of the nerve had a negative effect on outcome. negative effect on outcome.

•• Neither the type of the compressive vessel nor its Neither the type of the compressive vessel nor its location along or around the root was found to be location along or around the root was found to be significant. However, the severity of compression was significant. However, the severity of compression was importantimportant--the more severe the degree of compression, the more severe the degree of compression, the better the outcome (p = 0.002). the better the outcome (p = 0.002).

Endoscopic vascular decompression versus Endoscopic vascular decompression versus microvascularmicrovasculardecompression of the trigeminal nervedecompression of the trigeminal nerve

KabilKabil MS, MS, EbyEby JB, JB, ShahinianShahinian HK: Minimally Invasive Neurosurgery. 48(4):207HK: Minimally Invasive Neurosurgery. 48(4):207--12, 2005.12, 2005.

•• 255 patients who underwent EVD of the trigeminal 255 patients who underwent EVD of the trigeminal nervenerve

•• Initial, complete, postoperative success rate in 95 % of Initial, complete, postoperative success rate in 95 % of patients (3 months & no medications)patients (3 months & no medications)

•• 118 patients 118 patients -- 93 % complete success rate at least a three93 % complete success rate at least a three--year followyear follow--up period. up period.

•• Complication rates were compared to those reported for Complication rates were compared to those reported for MVD. There were no serious complications or mortality MVD. There were no serious complications or mortality in this series. in this series.

Gamma Knife UnitGamma Knife Unit

Gamma Knife Gamma Knife radiosurgeryradiosurgery for treatment of trigeminal for treatment of trigeminal neuralgia: idiopathic and tumor related neuralgia: idiopathic and tumor related

Young RF, et al: Neurology, 1997. Young RF, et al: Neurology, 1997. MaciewiczMaciewicz, Scrivani (Editorial), Scrivani (Editorial)

•• 51 patients with trigeminal neuralgia unrelated to tumors 51 patients with trigeminal neuralgia unrelated to tumors •• 38 of 51 patients (74.5%) were completely free of pain and 38 of 51 patients (74.5%) were completely free of pain and

eventually all medications were tapered off. eventually all medications were tapered off. •• An additional seven patients (13.7%) experienced An additional seven patients (13.7%) experienced

reductions in pain from 50 to 90% and utilized little or reductions in pain from 50 to 90% and utilized little or no medications. no medications.

•• Mean FU of 16.3 months (range 6Mean FU of 16.3 months (range 6--36 months) after 36 months) after treatment, 41 patients (80.4%) remained paintreatment, 41 patients (80.4%) remained pain--free or had free or had marked pain reduction. marked pain reduction.

•• No patient experienced either loss of facial sensation or No patient experienced either loss of facial sensation or any other complication any other complication

Gamma Knife Gamma Knife RadiosurgeryRadiosurgeryBrismanBrisman R, et al: Neurosurgery, 2000.R, et al: Neurosurgery, 2000.

•• ExcellentExcellent –– 49/81 (60%) 49/81 (60%)

•• GoodGood –– 23/81 (28%)23/81 (28%)

•• PoorPoor –– 4/81 (5%)4/81 (5%)

•• FailureFailure –– 5/81 (7%)5/81 (7%)

*Second GKR *Second GKR –– 4/81 (5%)4/81 (5%)

3 of 4 (75%) had M.S.3 of 4 (75%) had M.S.

Latency interval = 1 day Latency interval = 1 day –– 3 months 3 months

•• Paresthesia/dysesthesiaParesthesia/dysesthesia –– 8/81 (10%)8/81 (10%)

•• Anesthesia Anesthesia –– 00

•• Anesthesia dolorosa Anesthesia dolorosa –– 00

•• No shortNo short--term complications (0term complications (0--7 days)7 days)

GKRGKRRogers CL, Rogers CL, ShetterShetter AG, Fiedler JA, Smith K, Han PP, AG, Fiedler JA, Smith K, Han PP, SpeiserSpeiser BL: BL: IntInt J J

RadiatRadiat OncolOncol BiolBiol Phys, 2000.Phys, 2000.

•• 19971997--2000: 54 patients2000: 54 patients•• 3535--40 40 GyGy..•• Excellent/good/fair/poor (BNI pain index)Excellent/good/fair/poor (BNI pain index)•• Median FU= 12 mo. (3Median FU= 12 mo. (3--28)28)•• 52/54 (96%) experienced some pain relief??52/54 (96%) experienced some pain relief??19/54 (35%) = excellent19/54 (35%) = excellent3/54 (6%) = good3/54 (6%) = good26/54 (48%) = fair26/54 (48%) = fair4/54 (7%) = poor4/54 (7%) = poor

GKRGKRKondziolkaKondziolka D, D, LundsfordLundsford D, D, FlickingerFlickinger JC: JC: ClinClin J Pain, 2002.J Pain, 2002.

•• 19921992--2002: 220 patients2002: 220 patients•• 135 (61.4%) had prior surgery135 (61.4%) had prior surgery•• Median dose= 80 Median dose= 80 GyGy (60(60--90)90)•• Median FU= 2 yrs. (max.= 6.5 yrs.)Median FU= 2 yrs. (max.= 6.5 yrs.)•• Complete or partial pain relief = 85.6% at 1 Complete or partial pain relief = 85.6% at 1

year and 55.8% at 5 yearsyear and 55.8% at 5 years•• 10% developed new or increased subjective 10% developed new or increased subjective

facial numbnessfacial numbness

Gamma knife Gamma knife radiosurgeryradiosurgery for trigeminal neuralgia: for trigeminal neuralgia: results and potentially predictive parametersresults and potentially predictive parameters----part I: part I:

Idiopathic trigeminal neuralgia.Idiopathic trigeminal neuralgia.LonghiLonghi M, Rizzo P, M, Rizzo P, NicolatoNicolato A, A, ForoniForoni R, Reggio M, R, Reggio M, GerosaGerosa M: Neurosurgery. 61:1254M: Neurosurgery. 61:1254--1260, 20071260, 2007

•• 160 patients with TN were included in this study160 patients with TN were included in this study•• In 92 patients, GKR represented the first nonmedical option In 92 patients, GKR represented the first nonmedical option

("primary GKR"). In 68 patients, invasive treatments had been ("primary GKR"). In 68 patients, invasive treatments had been previously attempted. previously attempted.

•• Treatment outcome results were classified as: Treatment outcome results were classified as: Grade I (painGrade I (pain--free with no pharmacological treatment), free with no pharmacological treatment), Grade II (painGrade II (pain--free with pharmacological treatment), and free with pharmacological treatment), and Grade III (no result). Grade III (no result).

•• Grade I = 98/160 (61%) Grade I = 98/160 (61%) Grade II = 45/160 (29%)Grade II = 45/160 (29%)Grade III = 17 (10%) Grade III = 17 (10%)

•• Favorable prognostic factors include "primary GKR" and Favorable prognostic factors include "primary GKR" and maximal GKR dose ranging between 80 and 90 maximal GKR dose ranging between 80 and 90 GyGy..

MicrovascularMicrovascular decompression vs. gamma knife decompression vs. gamma knife radiosurgeryradiosurgery for typical trigeminal neuralgia: for typical trigeminal neuralgia:

preliminary findings.preliminary findings.BrismanBrisman R: Stereo & R: Stereo & FunctFunct NeurosurgNeurosurg. 85:94. 85:94--98, 2007.98, 2007.

•• Prospectively evaluated with a uniform protocol. Prospectively evaluated with a uniform protocol.

•• 24 patients were treated with MVD and 61 with GKR. 24 patients were treated with MVD and 61 with GKR.

•• Complete pain relief (no pain, no medicines) [12 and 18 Complete pain relief (no pain, no medicines) [12 and 18 months]:months]:

MVD MVD –– 68% and 68% 68% and 68%

GKR GKR –– 58% and 24% (p = 0.089)58% and 24% (p = 0.089)

•• There were no permanent complications. There were no permanent complications.

•• MVD is more likely than GKR to result in complete MVD is more likely than GKR to result in complete pain relief. pain relief.

CyberknifeCyberknife RadiosurgeryRadiosurgery

CyberKnifeCyberKnife radiosurgeryradiosurgery for idiopathic for idiopathic trigeminal neuralgiatrigeminal neuralgia

Lim M, Villavicencio AT, Lim M, Villavicencio AT, BurneikieneBurneikiene S, Chang SD, S, Chang SD, RomanelliRomanelli P, McNeely L, McIntyre M, P, McNeely L, McIntyre M, ThramannThramann JJ, Adler JJ, Adler JR: Neurosurgical Focus. 18(5):E9, 2005.JR: Neurosurgical Focus. 18(5):E9, 2005.

•• 41 patients41 patients•• 38 (92.7%) experienced initial pain relief at a median of 7 days38 (92.7%) experienced initial pain relief at a median of 7 days

after treatment (range, 24 hoursafter treatment (range, 24 hours--4 months). 4 months). Excellent Excellent -- 36 patients (87.8%)36 patients (87.8%)Moderate Moderate -- 2 (4.9%)2 (4.9%)No change No change -- 3 (7.3%) 3 (7.3%)

•• 6 (15.8%) of the 38 patients with initial relief experienced a 6 (15.8%) of the 38 patients with initial relief experienced a recurrence of pain at a median of 6 months (range 2recurrence of pain at a median of 6 months (range 2--8 8 months). months).

•• 32 (78%) had pain relief at mean of 11 months.32 (78%) had pain relief at mean of 11 months.•• 21 (51.2%) experienced numbness after treatment. 21 (51.2%) experienced numbness after treatment.

ELECTRICAL STIMULATIONELECTRICAL STIMULATION

•• TENSTENS•• Peripheral Nerve Stimulation (Implant)Peripheral Nerve Stimulation (Implant)

Trigeminal nerve branchesTrigeminal nerve branchesGreater occipital nerveGreater occipital nerve

•• Trigeminal Ganglion StimulationTrigeminal Ganglion Stimulation•• Deep Brain StimulationDeep Brain Stimulation•• Brainstem Stimulation (Trigeminal tract)Brainstem Stimulation (Trigeminal tract)•• Motor Cortex StimulationMotor Cortex Stimulation

Complementary and Alternative Complementary and Alternative Medicine (CAM)Medicine (CAM)

•• MeditationMeditation•• HypnosisHypnosis•• Guided ImageryGuided Imagery•• BiofeedbackBiofeedback•• Relaxation TherapyRelaxation Therapy•• CBTCBT•• Prayer and SpiritualityPrayer and Spirituality•• HomeopathyHomeopathy•• TCMTCM•• Bodywork and Movement Bodywork and Movement

TherapyTherapy

•• AcupunctureAcupuncture•• AyurverdicAyurverdic MedicineMedicine•• Physical MedicinePhysical Medicine•• Chiropractic TherapyChiropractic Therapy•• Energy MedicineEnergy Medicine•• Dietary MedicineDietary Medicine•• Herbal MedicineHerbal Medicine•• Massage TherapyMassage Therapy•• NaturopathyNaturopathy•• Neural TherapyNeural Therapy•• Magnet TherapyMagnet Therapy

NonNon--Pharmacological TherapyPharmacological Therapy

•• Biofeedback/Relaxation TherapyBiofeedback/Relaxation Therapy

•• Manual lymph drainage massage therapyManual lymph drainage massage therapy

•• B group vitaminsB group vitamins

•• Acupuncture (50Acupuncture (50--80% success)80% success)

•• BloodBlood--letting puncture (1997)letting puncture (1997)

Not herbal remediesNot herbal remedies