Diagnosis and Management of Craniofacial Pain

Richard K. Osenbach, M.D.

Director, Neurosurgical Services

Cape Fear Valley Medical Center

Key Points

All facial pain IS NOT trigeminal neuralgia

There are no tests for trigeminal neuralgia or for that matter most causes of facial pain

The wrong diagnosis can lead to the wrong treatment

Despite all the advancements in medicine, it is not possible to cure all pain problems

Approach to the patient with craniofacial pain

Specific pain syndromes

Pharmacological Management

Surgical Treatments

Approach to the Patient with Craniofacial Pain

Single most important aspect is to ESTABLISH THE CORRECT DIAGNOSISCareful detailed pain history

LocationDurationTemporal characteristicsQualitySeverityCircumstances of onsetInfluencing factorsNeurological symptomsResponse to medications

The more paroxysmal the pain, the more likely that surgery may be beneficial

Neuropathic Craniofacial Pain Syndromes

Trigeminal neuralgia

Trigeminal neuropathic

Postherpetic trigeminal pain

Glossopharyngeal neuralgia

Geniculate neuralgia

Occipital neuralgia

Sphenopalatine neuralgia

Vidian neuralgia

Superior laryngeal neuralgia

Carotidynia

Headache SyndromesClassic migraine

Common migraine

Migraine variants

Chronic daily headache

Cluster headache

Muscle tension headache

Post-traumatic headache

Chronic paroxysmal hemicrania

Headache caused by other disorders

Eg. Brain tumor, hydrocephalus, etc.

Ocular and Periocular Disorders

Tolosa-Hunt Syndrome

Raeder’s paratrigeminal syndrome

Orbital apex syndrome

Cavernous sinus syndrome

Parasellar syndrome

Corneal pathology

Angle closure glaucoma

Optic neuritis

Orbital cellulits

Otologic Problems

Otitis externa and interna

Ramsey-Hunt Syndrome

Bullous myringitis

Tumors

Mastoiditis

Dental and Periodontal Pathology

Periodontal abscess

Bruxism

Burning mouth syndrome

Temporomandibular joint disorders

What’s The Point?

SUCCESSFUL TREATMENT DEPENDS ON MAKING THE CORRECT DIAGNOSIS

Classification of Facial PainTrigeminal neuralgia, type 1, (TN1): facial pain of spontaneous onset with greater than 50% limited to the duration of an episode of pain (temporary pain).

Trigeminal neuralgia, type 2, (TN2): facial pain of spontaneous onset with greater than 50% as a constant pain.

Trigeminal neuropathic pain, (TNP): facial pain resulting from unintentional injury to the trigeminal system from facial trauma, oral surgery, ear, nose and throat (ENT) surgery, root injury from posterior fossa or skull base surgery, stroke, etc.

Trigeminal deafferentation pain, (TDP): facial pain in a region of trigeminal numbness resulting from intentional injury to the trigeminal system from neurectomy, gangliolysis, rhizotomy, nucleotomy, tractotomy, or other denervating procedures.

Symptomatic trigeminal neuralgia, (STN): pain resulting from multiple sclerosis.

Postherpetic neuralgia, (PHN): pain resulting from trigeminal Herpes zoster outbreak.

Atypical facial pain, (AFP): pain predominantly having a psychological rather than a physiological origin

Pharmacological TherapyAnti-epileptics drugs (AEDs)

Antidepressant medications

Opiates

Neuroleptics

Antispasmodics

Miscellaneous drugs

Botox

General Principles of Pharmacological Management

Rule out surgical lesions (tumor, etc.)

Neuropathic vs. nociceptive?

Develop a strategy

Lay out a plan

Conservative initial dosing to avoid side effects

Monotherapy is preferable if possible

Escalate dose to effect or toxicity

If second drug needed, choose agent in different class

Na+ channel blcoker, GABA agonist, etc.

Antiepileptic Agents

Tegretol (carbamazepine)

Trileptal (oxcarbazepine)

Neurontin (gabpentin)

Lyrica (pregabalin)

Dilantin (phenytoin)

Depakote (valproic acid)

Topamax (topirimate)

Lamictal

(lamotrigene)

Keppra (levateracitam)

Gabatril

Benzodiazepines

Antiepileptic Drugs (AEDS)

Similarities in pathophysiology of neuropathic pain and epilepsy

All AEDS ultimately act on ion channels

Efficacy of AEDS most clearly established for neuropathic conditions characterized by episodic lancinating pain

Most clinical studies have focused on DPN and PHN

Use of AEDS in patients with FBSS is nearly entirely empiric

AEDS Studied in Neuropathic Pain

Mechanisms of Selected AEDSCarbamazepine (Tegretol)

Modulates voltage-gated Na+ channels

Reduces spontaneous activity in experimental neuromas

Inhibits NE uptake; promotes endogenous descending inhibitory mechanisms

Oxcarbazepine (Trileptal)

Modulates Na+ and Ca+2 channels, incease K+ conductance

Lacks toxicity of epoxide metabolites

Lamotrigine

Blocks voltage-gated Na+ channels

Inhibits glutamate release from pre-synaptic neurons

Gabapentin (Neurontin)

Structural analog of GABA

Binds to voltage-dependent calcium channels

Inhibits EAA release; Interacts with NMDA receptor at glycine site

Pregabalin (Lyrica)

Binds to voltage-gated calcium channels

Adverse Effects of AEDsAllergic reaction

Up to 7% with CBZ

Some cross-reactivity between CBZ and PHT

Cognitive changes

Sedation

Nystagmus, ataxia, diplopia, dizziness

Nausea, vomiting, headache

Adverse Effects of 2nd Generation AEDS

Antidepressant Analgesics

“The results suggest to us that antidepressants may have an analgesic action which is independent of their mood-altering effects”

Merskey & Hester 1972

Descending Pain ModulationEndorphin link from PAG to pontine raphe nuclei

Serotonergic conection to spinal dorsal horn

Noradrenergic pathway from locus ceruleus to dorsal horn

Antidepressant AnalgesicsCurrent Evidence

Relieves all components of neuropathic painRCT - clear separation of analgesic and antidepressant effectsAlthough other agents (eg anti-epileptics)) may be regarded as 1st line therapy over antidepressants, there is no good evidence for this practiceMore selective agents are either less effective or not useful (serotonergic, noradrenergic)Because of incomplete efficacy, combination therapy may be neededComparative data regarding other drugs using NNT figures now exists

Antidepressants in Neuropathic Pain-RCT

Watson et al.: reviewed 29 randomized clinical trials

16 involved PHN or PDNMixed SN agents – 18/21 + effects

Amitriptyline 10/13, Imipramine 5/5,Doxepin 1/1, Venlafexline 2/2

NA – 10/12 + effectsNortriptyline 3/4, desipramine 4/5, maprotiline 2/2, bupropion 1/1

Serotonergic agents – 4/5 + effectsParoxetine 1/2, clomipramine 2/2, citalopram 1/1

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Adverse Effect of Antidepressants

Anti-cholinergic autonomic effects (TCAs)Allergic and hypresensitivity reactionsCardiovascular effects

Orthostatic hypotension (avoid imipramine in elderly)Quinidine-like cardiac effects

CNS effectsSedation, tremor, seizures, atropine-like delerium, exacerbation of schizophrenia/mania

Acute overdose may be fatal (>2000mg)Withdrawal reactions

Guidelines for Use of Antidepressants in Pain Management

Eliminate all other ineffective analgesicsStart low and titrate slowly to effect or toxicityNortriptyline or amitriptyline for initial treatmentMove to agents with more noradrenergic effectsConsider trazadone in patients with poor sleep patternTry more selective agents if mixed agents ineffectiveDo NOT prescribe monoamine oxidase inhibitorsTolerance to anti-muscarinic side effects usually takes weeks to developWithdraw therapy gradually to avoid withdrawal syndrome

Opioids for Chronic Non-Malignant Pain

Well-established and accepted for acute/cancer pain

Extrapolation of outcomes to non-malignant pain flawed

Information is more anecdotal, contradictory, philosophical, and/or emotional than scientific

Limited number of well-designed RCT with inconclusive results

Reduction in pain scores of around 20% without major benefits on function or psychological outcomes

Principles of Opioid Therapy in Chronic Non-Malignant Pain

Opioids provide analgesic benefit for a selected subpopulation of patients

Less evidence exists regarding improvement in function

Benefits outweigh risks in well-selected patients

Most benefit in patients with pain from established nociceptive/neuropathic conditions

Identification of other appropriate patients is problematic, and valid diagnostic criteria do not exist

Implementation of Opioid TherapyPrerequisites

Failure of pain management alternatives; but not a last resortOpioids should only be use as part of a multimodality approachIdentification of realistic goals of treatmentPhysical and psychosocial assessment by multidisciplinary teamConsider history of substance abuse as a relative contraindicationDecision to prescribe by multidisciplinary team or at least two practitionersInformed written consentBest practice – prescribe a trial of opioids and withdraw use if the provision of analgesia does not result in functional improvement

Implementation of Opioid TherapyTherapeutic Trial Period

Appropriate oral or transdermal drug selection

Defined trial period with regular assessment and review

Opioid dose adjustment or rotation as needed

Decision for long-term treatment predicated upon demonstration of pain relief and/or functional improvement

Implementation of Opioid TherapyLong-Term Therapy

Opioid contract

Single defined prescriber

Regular assessment and review

Routine urine and serum drug screen

Ongoing effort to improve physical, psychological, and social function as a result of pain relief

Continued multidisciplinary approach to pain

Defined responses to psychosocial or behavioral problems (addiction, diversion, etc)

Opioid Therapy - RCTPain Type Study Control Results

Nociceptive Arner & Meyerson, 1988 Placebo Pos

Kjaersgaard-Anderson, 1990 Paracetamol Pos***

Neuropathic Arner & Meyerson, 1988 Placebo Neg

Dellemijn & Vanneste, 1997 Placebo/Valium Pos

Kupers, et al., 1991 Placebo Pos

Rowbotham et al., 1991 Placebo Pos

Idiopathic Arner & Meyerson, 1988 Placebo Neg

Kupers, et al., 1991 Placebo Neg

Moulin et al., 1996 Benztropine Pos***

Unspecified Arkinstall et al., 1995 Placebo Pos***

Mays et al., 1987 Placebo/Bupiv Pos

Opioid Therapy – Prospective Uncontrolled Studies

Pain Type Reference Results

Nociceptive McQuay et al., 1992 Pos

Neuropathic Fenollosa et al., 1992 Pos

McQuay et al., 1992 Mixed

Urban et al., 1986 Pos

Idiopathic McQuay et al., 1992 Neg

Mixed/Unspecified Auld et al. 1985 Pos

Gilmann & Lichtigfeld, 1981 Pos

Penn and Paice, 1987 Pos

Plummer et al., 1991 Mixed

Adverse Effects of Opioids

Common Occasional Rare

Nausea/vomiting Hallucinations Respiratory dep.

Constipation Myoclonus Seizures

Urinary retention Mood changes Delerium

Sedation Anxiety Hyperalgesia

Cognitive impairment Rigidity Allodynia

Pruritis Dry mouth

Gastric stasis

Bronchoconstriction

Tolerance, Physical Dependence, Addiction

Miscellaneous AgentsAntiarrhythmics - Mexilitene

Na+ channel blockade Reduce neuronal hyperexcitabilityPossible predictive effect of IV lidocaine challengeMay worsen AV conduction blockMonitor EKG, LFT, renal fxnSignificant incidence of treatment-limiting side effects

Baclofen

GABAB receptor antagonistEfficacious in TNStart 10mg QD and titrate until effect or sedationCannot abruptly withdraw drug!

Trigeminal Branch Stimulation

Trigeminal Branch StimulationStimulation of supraorbital, infraorbital nerves

Indications

Trigeminal neuropathic pain

Trigeminal deafferentation pain

Post-herpetic neuralgia

Chronic daily headache

Peripheral Trigeminal Branch Stimulation for Neuropathic Pain

Johnson M, Burchiel K, Neurosurgery, 2004

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Pain Relief

Medication Use Patient Satisfaction

Peripheral Trigeminal Branch Stimulation for Neuropathic Pain

Effective for trigeminal neuropathic pain

Less effective for PHN

Simple, low morbidity

Pain relief seems relatively durable

Major problem is erosion of connector

Motor Cortex Stimulation

Motor cortex stimulation is NOT FDA approved and represents an off-label use of the implanted device

History of MCS

Developed by Tsubokawa and colleagues during 1980sTreatment of central deafferentation pain

Poststroke painThalamic painBulbar pain

Alternative to other methods of neuromodulation forSCSDBS

Discovered that stimulation of motor rather than sensory cortex produced better pain relief

Nociceptive Input(Spinothalamic System)

Non-noxious Input(DCML System)

DorsalHorn

SensoryCortex

Thalamus

DCN

Thalamus

SensoryCortex

MotorCortex

InInhibitory

Inhibitory

Inhibitory

Relationship Between Spinothalamic and DCML System - Normal

Nociceptive Input(Spinothalamic System)

Non-noxious Input(DCML System)

DorsalHorn

SensoryCortex

Thalamus

DCN

Thalamus

SensoryCortex

MotorCortex

InInhibitory

Inhibitory

Facilitation

PNS AA, C-fiber

Thalamic Pain

Motor Cortex StimulationClinical Indications

Post-stroke pain

Post-herpetic neuralgia

Trigeminal neuropathic pain

Trigeminal deafferentation pain

Transcranial Magnetic Stimulation

VAPSPre VAPSPost

Sham 7.0 + 0.6 6.5 + 0.6

0.5 Hz TMS 6.4 + 0.7 5.5 + 0.7

10 Hz TMS 7.3 + 0.5 4.8 + 0.8

Localization of Motor Cortex

Complications

Stimulation-induced seizures

Pain at stimulation site

Epidural hematoma

CSF leak

Electrode fracture or migration

Infection

Results of MCSNguyen et. al.: Arch Med Res, 2000

32 patients with central or peripheral neuropathic pain

Mean follow-up 27 months

Substantial pain relief achieved in:

77% (10/13) with central pain

83% (10/12) with neuropathic facial pain

Satisfactory results in 1/3 patient with SCI pain, 1 patient with PHN, 1 patient with plexus avulsion

No patient developed seizures

Results of MCS

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Pre-Op VAS VAS 3 months VAS long-term

Unanswered Questions

What are the best indications for MCS?What is the value of preoperative pharmacological testing?Is there a predictive value to TMS?What is the optimum electrode location?Is there any value to using multiple electrodes?Are there optimum stimulation parameters?How often should stimulation be applied and for how long?Can long-term reduction in pain be explained by adaptation of the brain to chronic stimulation?

Deep Brain Stimulation

Deep brain stimulation is NOT FDA approved for pain and represents an off-label use of the implanted device

Stimulation-Produced Analgesia

Reynolds, 1969: scienceElectrical stimulation of rat midbrain results in profound analgesia without concurrent administration of analgesic drugs

Relationship between SPA and endogenous opioid system

Richardson, 19731st published report of PAG-PVG stimulation in humans

DBS Pain TargetsPVG AND PAG

Activation of endogenous opiate systemsDescending modulatory pathwaysBest for nociceptive pain

LEMNISCAL SYSTEMVc (VPL,VPm) nucleus, medial lemniscus, ICParesthesia-producing stimulation Best for neuropathic pain

Results of DBSOverall results variable

30% to 85% excellent/good pain relief

Richardson (Neurosurgery, 1977)

85% effective short-term; 65% at 1 year

Gybels & Kupers (Neurophys Clin, 1990)

initial 61%; 4 years 30%

Plotkin (Appl Neurophys, 1982)

60-65% good results

Results of Deep Brain Stimulation Gybels and Kupers

Literature review through 1998

1,863 patients (38 reports)

Latest results analyzed

Success defined as:

Pain relief scores of 50% or more

Verbal ratings of “good” or “excellent”

Lack of relief during trial considered failure

Deep Brain Stimulation Deafferentation Pain

Electrode Site No. Long-Term Success %

PAG-PVG 155 35 23

VPL-VPM 409 228 56

Overall 644 349 54

Deep Brain Stimulation Nociceptive Pain

Electrode Site No. Long-Term Success %

PAG-PVG 291 247 59

VPL-VPM 51 0 0

Overall 419 172 59

Pain Type vs. Site of Stimulation

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Nociceptive pain Deafferentation pain

PAG-PVG VPL-VPM Overall

Deep Brain StimulationComplications

NeurologicIntracranial hemorrhage 1 - 5%Infection 3 -14%Seizures 3 - 4%

Device-related 2 - 26%Lead fractureLead migration

Stimulation-relatedUsually transient, resolve with adjustments to stimulationHeadache, nausea, diplopia, vertica gaze palsy, nystagmus, uncomfortable paresthesias, unpleasant stimulation side effects

Cluster Headache

Unilateral headache syndrome

Pain mainly located in orbitotemporal region

Abrupt onset and cessation

Pain last 15 – 3 hours (HIS criteria)

One or multiple attacks per day

Autonomic symptoms

“Cluster periods” lasting weeks to months

Episodic or chronic forms

Surgical Treatment for Cluster Headache

Microvascular decompression of trigeminal nerve

Ablative trigeminal procedures

RF rhizotomy

Glycerol rhizolysis

Stereotactic radiosurgery

Section of nervus intermedius

Destruction of sphenopalatine ganglion

Deep brain stimulation

Proposed Eligibilty Criteria for DBS in Patients with Cluster HA

Diagnosis of CH according to HIS criteriaSymptoms present at least 24 monthsCH attacks on daily basis

Symptoms strictly unilateralAll state-of-the-art medications have been tried singly or in combination“Normal psychological profileNo medical/neurological contraindications to DBSNormal neurological exam and imaging studiesPatient agrees to discontinue smoking and/or EtOH consumption

DBS for Cluster Headache“Stimulation of the Posterior Hypothalamus for Treatment of Chronic Intractable Cluster Headache: First Reported Series” Neurosurgery (2003)

Stim. Parameters: Amp=.7-3V, PW=60, Rate=180 Hz

Nucleus Caudalis DREZ Procedure

Indications for Caudalis DREZ

Trigeminal deafferentation pain (following RF lesion)Recurrent refractory trigeminal neuralgiaTrigeminal neuropathic pain (post-traumatic)Post-herpetic neuralgiaCentral pain following brainstem infarctionCluster headacheIntractable migraine headacheAtypical facial painCancer pain

Anatomical Landmarks

Caudalis DREZ ResultsVAS Scores

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Pre-op VAS 7.6 9.5 8.7 8.8

Post-op VAS 6.1 6.6 8.4 7.6

AFP PHN TN Overall

Caudalis DREZ ResultsPercent Improvement

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Late 48 41 29 30

AFP PHN TN Overall

Occipital Neuralgia and Occipital Headache

Syndromes

Occipital NeuralgiaPain within the distribution of the greater and/or lesser occipital nerves

Neuralgic variant

Sharp, shooting, electric-like pain

Almost always unilateral

Bursts of pain lasting for several seconds to few minutes

Non-neuralgic variant

Dull, aching, throbbing, pounding pain

More constant pain

Often bilateral

Sensory dysfunction in C2 nerve territory

Responds to local blockade of occipital nerve

Causes of Occipital NeuralgiaIdiopathicPost-traumaticSpinal Disorders

C1 fractureC1-2 instabilityRA with cranial settlingC1-2 arthrosis syndromeHypertrophic facet joint

Inflammatory disorders

Post-OperativeVP shuntRetromastoid craniectomyMastoidectomy

Chiari malformationMetabolic disordersVascular lesionsTumors

Evaluation: Plain X-rays, CT, MRI

Chiari I Malformation

Basilar Invagination

Schwannoma of GON

Intradural Schwannoma

Chronic Daily Headache

Chronic migraine subset

Headache present at least 15 days per month

Near daily to continuous pain

Incidence 4% to 5%

Up to 50% unresponsive to medication

OCCIPITAL NERVE STIMULATION FOR OCCITAL

HEADACHE SYNDROMES

Indications for ONS

Appropriate clinical condition

Condition refractory to non-operative therapy

Acceptable psychological profile

Positive response to local anesthetic block

Positive response to temporary stimulation trial

ONS - Technique

ONS – Electrode Position

Complications of ONS

Infection

Connector erosion

Electrode migration

Electrode fracture

Motor stimulation

Stimulation tolerance

130 patients

Average duration of symptoms – 8 years

Unilateral – 88; Bilateral – 42

Mean VAS score – 9.2 (5-10)

Occipital Nerve Stimulation Outcome

Weiner, R

Results of ONS

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Chronic Migraine

Cluster Headache

(May, Bahra, Buchel, Frackowiak & Goadsby, Lancet 1998)