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 DIAGNOSIS

Careful detailed pain history Location Duration Temporal characteristics Quality Severity Circumstances of onset Influencing factors Neurological symptoms Response 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 Syndromes

Classic 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 Pain

Trigeminal 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 Therapy

Anti-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 AEDS

Carbamazepine (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 AEDs

Allergic 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 2 nd 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 Modulation

Endorphin link from PAG to pontine raphe nuclei Serotonergic conection to spinal dorsal horn Noradrenergic pathway from locus ceruleus to dorsal horn

Antidepressant Analgesics

Current Evidence

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

Antidepressants in Neuropathic Pain-RCT Watson et al.: reviewed 29 randomized clinical trials

100

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

80

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

60

2/2 NA – 10/12 + effects

40

Nortriptyline 3/4, desipramine 4/5, maprotiline 2/2, bupropion 1/1

20

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

0 86 Mixed NS 83 NA 80 Ser

Adverse Effect of Antidepressants

Anti-cholinergic autonomic effects (TCAs) Allergic and hypresensitivity reactions Cardiovascular effects Orthostatic hypotension (avoid imipramine in elderly) Quinidine-like cardiac effects CNS effects Sedation, 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 analgesics Start low and titrate slowly to effect or toxicity Nortriptyline or amitriptyline for initial treatment Move to agents with more noradrenergic effects Consider trazadone in patients with poor sleep pattern Try more selective agents if mixed agents ineffective Do

NOT

prescribe monoamine oxidase inhibitors Tolerance to anti-muscarinic side effects usually takes weeks to develop Withdraw 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 Therapy

Prerequisites

Failure of pain management alternatives; but not a last resort Opioids should only be use as part of a multimodality approach Identification of realistic goals of treatment Physical and psychosocial assessment by multidisciplinary team Consider history of substance abuse as a relative contraindication Decision to prescribe by multidisciplinary team or at least two practitioners Informed written consent Best practice – prescribe a trial of opioids and withdraw use if the provision of analgesia does not result in functional improvement

Implementation of Opioid Therapy

Therapeutic 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 Therapy

Long-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)

Pain Type

Nociceptive Neuropathic Idiopathic Unspecified

Opioid Therapy - RCT

Study

Arner & Meyerson, 1988 Kjaersgaard-Anderson, 1990 Arner & Meyerson, 1988 Dellemijn & Vanneste, 1997 Kupers, et al., 1991 Rowbotham et al., 1991 Arner & Meyerson, 1988 Kupers, et al., 1991 Moulin et al., 1996 Arkinstall et al., 1995 Mays et al., 1987

Control

Placebo Paracetamol Placebo Placebo/Valium Placebo Placebo Placebo Placebo Benztropine Placebo Placebo/Bupiv

Results

Pos Pos***

Neg

Pos Pos Pos

Neg Neg

Pos*** Pos*** Pos

Pain Type

Nociceptive Neuropathic

Opioid Therapy – Prospective Uncontrolled Studies

Idiopathic Mixed/Unspecified

Reference

McQuay et al., 1992 Fenollosa et al., 1992 McQuay et al., 1992 Urban et al., 1986 McQuay et al., 1992 Auld et al. 1985 Gilmann & Lichtigfeld, 1981 Penn and Paice, 1987 Plummer et al., 1991

Results

Pos Pos

Mixed

Pos

Neg

Pos Pos Pos

Mixed

Adverse Effects of Opioids

Common

Nausea/vomiting Constipation Urinary retention Sedation Cognitive impairment Pruritis

Occasional

Hallucinations Myoclonus Mood changes Anxiety Rigidity Dry mouth Gastric stasis Bronchoconstriction

Rare

Respiratory dep.

Seizures Delerium Hyperalgesia Allodynia

Tolerance, Physical Dependence, Addiction

Miscellaneous Agents

Antiarrhythmics - Mexilitene Na + channel blockade Reduce neuronal hyperexcitability Possible predictive effect of IV lidocaine challenge May worsen AV conduction block Monitor EKG, LFT, renal fxn Significant incidence of treatment-limiting side effects Baclofen GABA B receptor antagonist Efficacious in TN Start 10mg QD and titrate until effect or sedation Cannot abruptly withdraw drug!

Trigeminal Branch Stimulation

Trigeminal Branch Stimulation

Stimulation 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

8 6 4 2 0 6 4 2 0 0 25 50 Pain Relief Increase No Change Medication Use 75 100 Reduced 3 2 5 4 1 0 Slightly Somewhat Mostly Patient Satisfaction Completely

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 1980s Treatment of central deafferentation pain Poststroke pain Thalamic pain Bulbar pain Alternative to other methods of neuromodulation for SCS DBS Discovered that stimulation of motor rather than sensory cortex produced better pain relief

Motor Cortex Sensory Cortex Thalamus Dorsal Horn Inhibitory Sensory Cortex Inhibitory Thalamus DCN InInhibitory Nociceptive Input (Spinothalamic System) Non-noxious Input (DCML System) Relationship Between Spinothalamic and DCML System - Normal

Thalamic Pain A



, C-fiber PNS A



Motor Cortex Stimulation

Clinical Indications

Post-stroke pain Post-herpetic neuralgia Trigeminal neuropathic pain Trigeminal deafferentation pain

Transcranial Magnetic Stimulation

Sham 0.5 Hz TMS 10 Hz TMS VAPS Pre 7.0 + 0.6

6.4 + 0.7

7.3 + 0.5

VAPS Post 6.5 + 0.6

5.5 + 0.7

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 MCS

Nguyen 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

VAS score 100 90 80 70 60 50 40 30 20 10 0 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: science Electrical stimulation of rat midbrain results in profound analgesia without concurrent administration of analgesic drugs Relationship between SPA and endogenous opioid system Richardson, 1973 1 st published report of PAG-PVG stimulation in humans

DBS Pain Targets

PVG AND PAG

Activation of endogenous opiate systems Descending modulatory pathways Best for nociceptive pain

LEMNISCAL SYSTEM

Vc (VPL,VPm) nucleus, medial lemniscus, IC Paresthesia-producing stimulation Best for neuropathic pain

Results of DBS

Overall 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

PAG-PVG VPL-VPM Overall

No.

Long-Term Success

155 409 644 35 228 349

%

23 56 54

Deep Brain Stimulation

Nociceptive Pain

Electrode Site

PAG-PVG VPL-VPM Overall

No.

Long-Term Success

291 51 419 247 0 172

%

59 0 59

Pain Type vs. Site of Stimulation

60 50 40 Success Rate 30 20 10 0 Nociceptive pain PAG-PVG VPL-VPM Deafferentation pain Overall

Deep Brain Stimulation

Complications

Neurologic

Intracranial hemorrhage Infection Seizures

Device-related

Lead fracture Lead migration

Stimulation-related

1 - 5% 3 -14% 3 - 4% 2 - 26% Usually transient, resolve with adjustments to stimulation Headache, 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 criteria Symptoms present at least 24 months CH attacks on daily basis Symptoms strictly unilateral All state-of-the-art medications have been tried singly or in combination “Normal psychological profile No medical/neurological contraindications to DBS Normal neurological exam and imaging studies Patient 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 neuralgia Trigeminal neuropathic pain (post-traumatic) Post-herpetic neuralgia Central pain following brainstem infarction Cluster headache Intractable migraine headache Atypical facial pain Cancer pain

Anatomical Landmarks

Caudalis DREZ Results

VAS Scores

10 VAS Score 9 8 4 3 2 7 6 5 1 0 Pre-op VAS Post-op VAS AFP 7.6

6.1

PHN 9.5

6.6

TN 8.7

8.4

Overall 8.8

7.6

Caudalis DREZ Results

Percent Improvement

70 60 50 40 30 20 10 0 Immediate Late AFP 69 48 PHN 42 41 TN 14 29 Overall 32 30

Occipital Neuralgia and Occipital Headache Syndromes

Occipital Neuralgia

Pain 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 Neuralgia

Idiopathic Post-traumatic Spinal Disorders C1 fracture C1-2 instability RA with cranial settling C1-2 arthrosis syndrome Hypertrophic facet joint Inflammatory disorders Post-Operative VP shunt Retromastoid craniectomy Mastoidectomy Chiari malformation Metabolic disorders Vascular lesions Tumors

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

Occipital Nerve Stimulation

Outcome

130 patients Average duration of symptoms – 8 years Unilateral – 88; Bilateral – 42 Mean VAS score – 9.2 (5-10)

Weiner, R

50 45 40 35 30 25 20 15 10 5 0 Excellent Good

Results of ONS

5 4 3 2 1 0 10 9 8 7 6 Pre-Op VAS Post-Op VAS Fair Poor

Chronic Migraine

Cluster Headache

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