Post Herpetic Neuralgia, Post Herpetic Itch & Trigeminal ... Herpetic Nerua… · the treatment of post herpetic neuralgia, post herpetic itch, and trigeminal neuralgia. VARICELLA

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Paul G. Mathew, MD, FAHSDirector of Continuing Medical Education

John R. Graham Headache CenterBrigham & Women’s Hospital

Staff NeurologistHarvard Vanguard Medical Associates

Cambridge Health AllianceHarvard Medical School

Post Herpetic Neuralgia, Post Herpetic Itch & Trigeminal Neuralgia

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OBJECTIVES: Participants will be able to

accurately diagnose post herpetic neuralgia, post herpetic itch, and trigeminal neuralgia

Participants will be able to explain the pathophysiology and natural history of post herpetic neuralgia, post herpetic itch, and trigeminal neuralgia

Participants will be able to select the optimal medication and interventional techniques used for the treatment of post herpetic neuralgia, post herpetic itch, and trigeminal neuralgia

VARICELLA ZOSTER VIRUS

3CDC Website, Dr. Erskine Palmer; B.G. Partin

Electron micrograph of Varicella Zoster Virus

Primary infection leads to Chicken Pox– A disease affecting immunocompetent

children– Symptoms include fever, malaise,

pharyngitis, generalized vesicular rash– Prior to vaccination, 95% of adults

experienced Chickenpox Usually benign and resulted in long-

term immunity

CHICKEN POX

4CDC Website, American Academy of Pediatrics

Typical diffuse vesicular rash

VZV VACCINATION TIME LINE

Goldman GS, King PG. Review of the United States universal varicella vaccination program: Herpes zoster incidence rates, cost-effectiveness, and vaccine efficacy based primarily on the Antelope Valley Varicella Active Surveillance Project data. Vaccine. 2013 Mar 25;31(13):1680-94.

1995 vaccine introduced

2006, 20% of vaccinees were experiencing breakthrough Chicken Pox– Initial vaccine at 12-16 months– CDC recommended a booster dose for children 4-6 years

old

2007, a shingles vaccination was approved for adults aged 60 years and older

SHINGLES Latent virus in neurons of cranial nerve ganglia, dorsal root ganglia, or

autonomic ganglia

Reactivation in immunocompromised individuals and as humans undergo a natural decline in cell-mediated immunity to VZV with age

CHICKEN POX SHINGLES

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SHINGLES Hemorrhagic inflammation of the peripheral nerve, dorsal root, and dorsal

root ganglion.

Pain and rash usually occur within days of each other

Pain is severe and usually burning in quality, but can have lancinating spikes

Can involve allodynia as well as sensory loss

Can present without skin eruptions “zoster sine herpete “– Radicular/Trigeminal Pain Distribution– Confirmed with PCR for VZV in CSF

SHINGLES

9Wolff K, Johnson R, Fitzpatrick TB. Fitzpatrick’s color atlas and synopsis of clinical dermatology. 5th Ed. McGraw-Hill Education; 2005: 66.

Typical unilateral painful skin vesicular rash that erupt along the distribution of a nerve in a single dermatome

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SHINGLES EPIDEMIOLOGY Study of 1019 Patients over 8 years

– 60% women and 40% were men – Mean age of 58 years (range 9-96 years)– Prevalence varied between 1.3 and 1.6 per 1000 per year – Location

Thoracic dermatomes- 56% Cervical dermatomes- 17% Lumbar dermatomes- 10% Sacral dermatomes- 5% Trigeminal nerve- 12%.

– Most common in the summer and least common in the spring– Incidence is 5 to 10 times greater for those older than 80 years

Glynn C, Crockford G, Gavaghan D, Cardno P, Price D, Miller J. Epidemiology of shingles. J R Soc Med. 1990;83(10):617.

ZOSTER COMPLICATIONS Postherpetic neuralgia (PHN) is most common complication

Postherpetic Itch (PHI)– Thought to have similar pathophysiology as PHN– Treatment is similar to PHN but PHI can be more resistant to treatment– Antihistamines may have a role in the treatment of PHI – Topical steroids typically used for pruritus have

not proven to be effective

111. Jagdeo J1, Kroshinsky D. A case of post-herpetic itch resolved with gabapentin. J Drugs Dermatol. 2011 Jan;10(1):85-8.2. Semionov V, Shvartzman P. Post herpetic itching--a treatment dilemma. Clin J Pain. 2008 May;24(4):366-8.

ZOSTER COMPLICATIONS Zoster can also result in

– Meningoencephalitis– Myelitis– Herpes zoster ophthalmicus (acute or progressive outer retinal necrosis)– Herpes zoster oticus (Ramsay Hunt Syndrome)

Hearing loss and facial paralysis – VZV vasculopathy

Transient ischemic attacks, ischemic and hemorrhagic stroke Temporal artery infection mimicking giant cell arteritis Extracranial vasculopathy Aneurysm with and without subarachnoid hemorrhage Arterial dissection Ischemic cranial neuropathies Cerebral venous sinus thrombosis Spinal cord infarction Peripheral thrombotic disease.

12Nagel MA, Gilden D. Update on varicella zoster virus vasculopathy. Curr Infect Dis Rep. 2014 Jun;16(6):407.

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POST HERPETIC NEURALGIA RISK FACTORS

Risk of PHN after Shingles– < 60 years of age < 2 %– 60 to 69 years of age 6.9 %– >70 years 18.5 %

Other Risk factors– Greater pain– Greater rash– Immunocompromise

Helgason S, Petursson G, Gudmundsson S, Sigurdsson JA. Prevalence of postherpetic neuralgia after a first episode of herpes zoster: prospective study with long term follow up. BMJ. 2000;321(7264):794.

Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005;352(22):2271.

POST HERPETIC NEURALGIA NATURAL HISTORY

Natural history is variable– 43 subjects

6 months 14 with PHN

Median 3.9 years 2 with PHN

– 10 subjects assessed at median 7.7 1 with PHN at 6 months developed PHN between 3.9 and 7.7 year follow-up

– Many subjects had abnormal quantitative sensory testing in the absence of pain Suggestive of some fibrosis and demyelination

14Reda H, Greene K, Rice FL, Rowbotham MC, Petersen KL. Natural history of herpes zoster: late follow-up of 3.9 years (n=43) and 7.7 years (n=10). Pain. 2013 Oct;154(10):2227-33.

ACUTE TREATMENT OF SHINGLES Antiviral therapy for patients who present within 72 for seven days.

– Acyclovir 800 mg five times daily– Famciclovir 500 mg three times daily– Valacyclovir 1000 mg three times daily– Medication choice may be driven by cost and convenience

Benefit less clear after 72 hours– New lesion formation means ongoing viral replication– All lesions encrusted, likely outside of antiviral treatment window

Antiviral therapy tends to improve healing time of cutaneous lesions, decrease intensity/duration of neuritis, and reduced tendency to develop post herpetic neuraliga

Better data for patients >50

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Wood MJ, Kay R, Dworkin RH, Soong SJ, Whitley RJ. Oral acyclovir therapy accelerates pain resolution in patients with herpes zoster: a meta-analysis of placebo-controlled trials. Clin Infect Dis. 1996;22(2):341.

Tyring S, Barbarash RA, Nahlik JE, Cunningham A, Marley J, Heng M, Jones T, Rea T, Boon R, Saltzman R. Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia. A randomized, double-blind, placebo-controlled trial. Collaborative Famciclovir Herpes Zoster Study Group. Ann Intern Med. 1995;123(2):89.

ACUTE TREATMENT OF SHINGLES

Antiviral therapy + Glucocorticoids?– Meta-Analysis

5 randomized, double-blind, placebo-controlled parallel group studies 787 participants. Primary outcome: Presence of postherpetic neuralgia six months after rash onset No significant difference between corticosteroid plus antiviral agents and placebo plus

antiviral agents groups No significant difference in any serious adverse event (death, acute cardiac

insufficiency, rash dissemination, bacterial pneumonia or haematemesis) or non serious adverse event (dizziness, nausea, vomiting, hypertension or hyperglycaemia).

– Glucocorticoids may increase the risk of secondary skin infections

16He L, Zhang D, Zhou M, Zhu C. Corticosteroids for preventing postherpetic neuralgia. Cochrane Database Syst Rev. 2008.

POST HERPETIC NEURALGIA TREATMENT

17Massengill JS, Kittredge JL. Practical considerations in the pharmacological treatment of postherpetic neuralgia for the primary care provider. J Pain Res. 2014; 7: 125–132.

HERPETIC NEURALGIA TIME COURSE

Acute- pain preceding or accompanying rash that persists up to 30 days from its onset

Subacute- pain that persists after rash but which resolves within four months of onset

Post Herpetic Neuralgia- pain persisting beyond four months

18Arani RB1, Soong SJ, Weiss HL, Wood MJ, Fiddian PA, Gnann JW, Whitley R. Phase specific analysis of herpes

zoster associated pain data: a new statistical approach. Stat Med. 2001 Aug 30;20(16):2429-39.

POST HERPETIC NEURALGIA TREATMENT

The American Academy of Neurology Quality Standards Subcommittee found the following agents effective in reducing the pain of post herpetic neuralgia– Gabapentin– Pregabalin– Tricyclic antidepressants– Lidocaine patch– Opioids

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Dubinsky RM, Kabbani H, El-Chami Z, Boutwell C, Ali H; Quality Standards Subcommittee of the American Academy of Neurology.Practice parameter: treatment of postherpetic neuralgia: an evidence-based report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2004 Sep 28;63(6):959-65.

POST HERPETIC NEURALGIA ORAL TREATMENT

Gabapentin– FDA approved

1993: Adjunctive therapy for adult partial seizures 2002: Post-herpetic neuralgia

– Used for the treatment of pain, alterations of sensation, and pruritus associated with dermatological conditions

– Dosing typically starts at 100mg HS– A dose of 1800 mg/day proved to be effective over 6 randomized clinical

trials– Dosing can reach 1200mg TID– Side Effects: somnolence, peripheral edema, and weight gain– Available in an extended release formulation for daily dosing

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1. Scheinfeld N. The role of gabapentin in treating diseases with cutaneous manifestations and pain. Int J Dermatol. 2003 Jun;42(6):491-5.2. Fan H, Yu W, Zhang Q, Cao H, Li J, Wang J, Shao Y, Hu X. Efficacy and safety of gabapentin 1800 mg treatment for post-herpetic neuralgia: a meta-analysis of randomized controlled trials. J Clin Pharm Ther. 2014 May 8.

POST HERPETIC NEURALGIA ORAL TREATMENT Pregablin

– FDA approved for 2004: Post herpetic neuralgia 2004: Diabetic peripheral neuropathy 2004: Adjunctive therapy for adult partial seizures 2007: Fibromyalgia

– Dosing typically starts at 25mg HS– Doses of 300-600 mg/day have demonstrated efficacy for PHN

Usually dosed BID– Side Effects: somnolence, peripheral edema, and weight gain– Often requires a prior authorization and a failed trial of gabapentin

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Dworkin RH, Corbin AE, Young JP Jr, Sharma U, LaMoreaux L, Bockbrader H, Garofalo EA, Poole RM . Pregabalin for the treatment of postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology. 2003 Apr 22;60(8):1274-83.

POST HERPETIC NEURALGIA ORAL TREATMENT

Tricyclic Antidepressants– Amitriptyline, Nortriptyline, and Desipramine are the most commonly used

agents– Amitriptyline FDA approved in 1961 for Depression– Cochrane 21 study analysis

No supportive unbiased evidence for a beneficial effect Decades of successful treatment of neuropathic pain and fibromyalgia There is no good evidence of a lack of effect

– Dosing typically starts at 10mg HS– Doses of 150mg HS have demonstrated some efficacy for neuropathic

pain of many types including PHN – Depression dosing can reach 300mg HS– Side Effects: Sedation, Weight Gain, Dry Mouth, Dry Eyes, Glaucoma

Exacerbation, QT prolongation

22Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ. Amitriptyline for neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2012 Dec 12;12:CD008242. 22

POST HERPETIC NEURALGIA TOPICAL & SYSTEMIC TREATMENT

PHN patients tend to be elderly or immunocompromised – Multiple medical conditions

Hepatic and renal issues affect pharmacokinetics Psychiatric co-morbidities may increase chances of adverse events

– Multiple medications

Topical therapies lack systemic side effects and can be used in place or in addition to oral systemic agents

Refractory cases may require oral polypharmacy in addition to topical agents

23Bruckenthal P, Barkin RL. Options for treating postherpetic neuralgia in the medically complicated patient. Ther Clin Risk Manag. 2013;9:329-40.

POST HERPETIC NEURALGIA TOPICAL TREATMENT

Capsaicin– Stimulates the transient receptor potential

cation channel subfamily V member 1 (TrpV1)– Derived from chili peppers – Initial stimulation causes intense burning, but

prolonged exposure leads to desensitization of local pain fibers Initial dose normally placed for 60 minutes under

local anesthesia Can cause first to third degree chemical burns at

application site– Benefits typically last for about 12 weeks

Repeated as needed

24Peppin JF, Pappagallo M. Capsaicinoids in the treatment of neuropathic pain: a review. Ther Adv Neurol Disord. 2014 Jan;7(1):22-32.


Capsaicin– Four studies involving 1272 participants

with PHN High concentration patch (8%) demonstrated

significant improvement of pain over placebo and low concentration capsaicin at 8 and 12 weeks

– Over the counter patch has a typical concentration of 0.025%

25Derry S, Sven-Rice A, Cole P, Tan T, Moore RA. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2013 Feb 28;2:CD007393.


Capsaicin Application

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The appropriate treatment of PHN neuropathic pain with a capsaicin patch

The inappropriate treatment of “pain not otherwise specified” with aerosolized capsacin (pepper spray)


Topical 5% Lidocaine– Patches applied for 12-24 hours at a time– Can be costly and insurance coverage can be difficult– Trials have yielded mixed results– 102 subjects

10 dropped out due to lack of efficacy 9 dropped out due to treatment-related adverse events 56 left the study for non-treatment-related reasons 27 still under treatment after 4 years 80% reported continued improvement of clinical global impression of change

(CGIC) and patients' global impression of change (PGIC) scores – Treatment overall found to be safe and well tolerated over years

27Sabatowski R1, Hans G, Tacken I, Kapanadze S, Buchheister B, Baron R. Safety and efficacy outcomes of long-term treatment up to 4 years with 5% lidocaine medicated plaster in patients with post-herpetic neuralgia. Curr Med Res Opin. 2012 Aug;28(8):1337-46.

POST HERPETIC NEURALGIA INJECTABLE TREATMENT

Botulinum Toxin (BTX) Injections– 30 subjects with PHN randomized BTX vs. Control

13/15 in BTX arm had a 50% reduction in visual analogue pain scores Benefit persisted for a median of 16 weeks

0/15 in control arm had a 50% reduction in visual analogue pain scores Safe and well tolerated

– 60 subjects with PHN randomized BTX vs. lidocaine 0.5% vs. saline BTX significantly decreased pain and reduced opioid use compared with

lidocaine and placebo at 3 months post-treatment.

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1. Apalla Z1, Sotiriou E, Lallas A, Lazaridou E, Ioannides D. Botulinum toxin A in postherpetic neuralgia: a parallel, randomized, double-blind, single-dose, placebo-controlled trial. Clin J Pain. 2013 Oct;29(10):857-64.

2. Xiao L1, Mackey S, Hui H, Xong D, Zhang Q, Zhang D. Subcutaneous injection of botulinum toxin a is beneficial in postherpetic neuralgia. Pain Med. 2010 Dec;11(12):1827-33.

POST HERPETIC NEURALGIA INJECTABLE TREATMENT

Intrathecal glucocorticoids– Intrathecal 3 ml of 3 percent lidocaine with 60 mg of methylprednisolone

Vs. Lidocaine Vs. No Treatment Control 270 Subjects per group 2/3 subjects received injections once per week x 4 weeks Use of pain medication decreased by 70% in mixed group

– Intrathecal found to be superior to epidural injections

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2. Kotani N, Kushikata T, Hashimoto H, Kimura F, Muraoka M, Yodono M, Asai M, Matsuki A. Intrathecal methylprednisolone for intractable postherpetic neuralgia.N Engl J Med. 2000;343(21):1514.3. Kikuchi A, Kotani N, Sato T, Takamura K, Sakai I, Matsuki A. Comparative therapeutic evaluation of intrathecal versus epidural methylprednisolone for long-term analgesia in patients with intractable postherpetic neuralgia. Reg Anesth Pain Med. 1999;24(4):287.

POST HERPETIC NEURALGIA OTHER TREATMENT OPTIONS

Opioids are typically adjunctive therapy and not first line– Tramadol, morphine, oxycodone, and methadone used

with mixed results– Physical dependence, tolerance, addiction, and

overdose

NMDA receptor antagonists– IV Ketamine provided some pain relief– Limited by IV access, sedation, dysphoria, and

dissociative episodes

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1. Gan EY, Tian EA, Tey HL. Management of herpes zoster and post-herpetic neuralgia. Am J Clin Dermatol. 2013 Apr;14(2):77-85.2. Eide PK, Jørum E, Stubhaug A, Bremnes J, Breivik H. Relief of post-herpetic neuralgia with the N-methyl-D-aspartic acid

receptor antagonist ketamine: a double-blind, cross-over comparison with morphine and placebo. Pain. 1994;58(3):347.

POST HERPETIC NEURALGIA OTHER TREATMENT OPTIONS Cryotherapy with liquid nitrogen

Thalamic stimulation

Electrocoagulation of the dorsal root

TENS

Intravenous lidocaine

Acupuncture

Peripheral Nerve Stimulation

3131

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TRIGEMINAL NEURALGIA (TN) DIAGNOSTIC CRITERIA A) At least three attacks of unilateral facial pain fulfilling criteria B and C

B) Occurring in one or more divisions of the trigeminal nerve, with no radiation beyond the trigeminal distribution

C) Pain has at least three of the following four characteristics:– Recurring in paroxysmal attacks lasting from a fraction of a second to two

minutes– Severe intensity– Electric shock-like, shooting, stabbing or sharp in quality– At least three attacks precipitated by innocuous stimuli to the affected side of

the face (some attacks may be, or appear to be, spontaneous)

●D) No clinically evident neurologic deficit

●E) Not better accounted for by another ICHD-3 diagnosis

Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013 Jul;33(9):629-808.

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TRIGEMINAL NEURALGIA FEATURES Triggered by trivial stimuli including washing, shaving,

smoking, talking and/or brushing the teeth (trigger factors) and frequently occurs spontaneously.

Usually involves the second or third divisions with first division involvement in <5% of patients


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TRIGEMINAL NEURALGIA FEATURES Between attacks the patient is usually pain free, but a dull

background pain may persist in some long-standing cases.

Between attacks, trigger zones remain inactive during refractory period


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TRIGEMINAL NEURALGIA FEATURES In some cases a paroxysm can be triggered from

somatosensory stimuli outside the trigeminal area, such as a limb, or by other sensory stimulation such as bright lights, loud noises or tastes.

Attack periods can last for weeks to months followed by remissions, but the pain usually returns

Usually responsive, at least initially, to pharmacotherapy


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TRIGEMINAL NEURALGIA FEATURES Pain can trigger a facial spasm hence the name tic douloureux TN does not typically involve unilateral autonomic features that

can be seen with Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT), short-lasting unilateral neuralgiform headache attacks with autonomic symptoms (SUNA)

Based on this image President Vladimir Putin is more likely to have SUNCT than TN


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TRIGEMINAL NEURALGIA EPIDEMIOLOGY

Annual incidence of TN is 4-13 per 100,000 people

Incidence increases with age, and most idiopathic cases occur to those over the age of 50

Male to female ratio of TN is about 1:1.7

Hypertension may be a risk factor

Katusic S, Williams DB, Beard CM, Bergstralh EJ, Kurland LT. Epidemiology and clinical features of idiopathic trigeminal neuralgia and glossopharyngeal neuralgia: similarities and differences, Rochester, Minnesota, 1945-1984. Neuroepidemiology. 1991;10(5-6):276.

Katusic S, Beard CM, Bergstralh E, Kurland LT. Incidence and clinical features of trigeminal neuralgia, Rochester, Minnesota, 1945-1984. Ann Neurol. 1990 Jan;27(1):89-95.

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“CLASSIC” TRIGEMINAL NEURALGIA Idiopathic

– Patients with possible compression not revealed on imaging or confirmed with surgery

Vascular Compression– Artery or vein near root entry zone of pons– Some estimates as high as 91% have vascular compression – Chronic compression thought to cause focal demyelination and aberrant

sensory impulses


Hamlyn PJ. Neurovascular relationships in the posterior cranial fossa, with special reference to trigeminal neuralgia. Neurovascular compression of the trigeminal nerve in cadaveric controls and patients with trigeminal neuralgia: quantification and influence of method. Clin Anat. 1997;10(6):380.

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TRIGEMINAL NEURALGIA RED FLAGS

According to the AAN and EFNS– Structural causes in up to 15% of patients – Features that increase risk of underlying lesion

Trigeminal sensory deficits Bilateral involvement of the trigeminal nerve Younger age

Gronseth G1, Cruccu G, Alksne J, Argoff C, Brainin M, Burchiel K, Nurmikko T, Zakrzewska JM. Practice parameter: the diagnostic evaluation and treatment of trigeminal neuralgia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the European Federation of Neurological Societies. Neurology. 2008 Oct 7;71(15):1183-90.

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TRIGEMINAL NEURALGIA TN due to secondary causes = Painful Trigeminal Neuropathy

– Acute herpes zoster/Postherpetic neuralgia Most commonly affects V1

– Post-traumatic trigeminal neuropathy– Multiple Sclerosis– Vestibular schwannoma/acoustic neuroma– Cerebellopontine Meningioma– Epidermoid or other cyst– Saccular aneurysm– Arteriovenous malformation


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TRIGEMINAL NEURALGIA PHARMACOTHERAPY

According to the AAN and EFNS– Carbamazepine (Level A, Established as effective)

100mg daily 600mg BID Test for HLA-B*1502 allele in patients of Asian ancestry

Stevens-Johnson syndrome and/or toxic epidermal necrolysis– Oxcarbazepine (Level B, Probably effective)

300mg daily 900mg BID– Baclofen (Level C, Possibly Effective)

5 mg PO q8hr 80 mg/day – Lamotrigine (Level C, Possibly Effective)

50mg daily 400mg daily– Phenytoin, Valproic acid, Gabapentin, Pregabalin, and

Topiramate have small study support

Gronseth G1, Cruccu G, Alksne J, Argoff C, Brainin M, Burchiel K, Nurmikko T, Zakrzewska JM. Practice parameter: the diagnostic evaluation and treatment of trigeminal neuralgia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the European Federation of Neurological Societies. Neurology. 2008 Oct 7;71(15):1183-90.

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TRIGEMINAL NEURALGIA PHARMACOTHERAPY

Other potentially agents with IV formulations, which may be useful in intractable cases and/or the ED

– Levetiracetam– Phenytoin– Valproic Acid

1. Tate R, Rubin LM, Krajewski KC. Treatment of refractory trigeminal neuralgia with intravenous phenytoin. Am J Health Syst Pharm. 2011 Nov 1;68(21):2059-61.

2. Zakrzewska JM1, Linskey ME. Trigeminal neuralgia. Clin Evid (Online). 2009 Mar 12;2009. pii: 1207.3. Mitsikostas DD1, Pantes GV, Avramidis TG, Karageorgiou KE, Gatzonis SD, Stathis PG, Fili VA, Siatouni AD,

Vikelis M. An observational trial to investigate the efficacy and tolerability of levetiracetam in trigeminal neuralgia. Headache. 2010 Sep;50(8):1371-7.

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TRIGEMINAL NEURALGIA BOTULINUM TOXIN INJECTIONS

Randomized controlled trial with 42 subjects with TN– 22 subjects received 75 units of BTX – 20 subjects received saline injections – Significant reduction in pain frequency at week 1 and intensity at week 2 – More responders in BTX group (68.18%) than in the placebo group

(15.00%). – BTX was well tolerated, with few treatment related adverse events at the

end of 12 weeks

Wu CJ1, Lian YJ, Zheng YK, Zhang HF, Chen Y, Xie NC, Wang LJ. Botulinum toxin type A for the treatment of trigeminal neuralgia: results from a randomized, double-blind, placebo-controlled trial. Cephalalgia. 2012 Apr;32(6):443-50.

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TRIGEMINAL NEURALGIA INTERVENTIONAL PROCEDURES In cases resistant to pharmacotherapy, there are multiple procedures that

can be used for the treatment of TN– Microvascular Decompression– Denervating/Destructive Procedures

Percutaneous Trigeminal Rhizotomy Radiofrequency, Glycerol, or Balloon

Stereotactic Radiosurgery Gamma Knife

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MICROVASCULAR DECOMPRESSION 2 inch craniotomy exposes area

posterior to ear

Under microscope, the superior cerebellar artery is decompressed from nerve, and teflon felt is placed in between

More invasive than other procedures, but no nerve destruction

Faster results and longer lasting

If no compression found, open denervation (microsurgical rhizotomy) could be performed

Destructive procedures could be considered in MVD failure

1. Pollock BE. Surgical management of medically refractory trigeminal neuralgia. Curr Neurol Neurosci Rep. 2012 Apr;12(2):125-31.

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RISKS OF NEUROSURGERY Highest rates of permanent

cranial nerve deficit

Meningitis/Encephalitis

Intracranial Hemorrhage/Stroke

Cranial Nerve Deficits/Neuralgias

CSF Leaks

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TRIGEMINAL NEURALGIA First denervating/destructive procedures were peripheral trigeminal

neurectomies– Caused dense numbness– Earlier recurrence of pain– Treated focused, small, superficial branch of TN

Proximal treatment (rhizotomy, root exit zone) has better results– Longer lasting– Less or no facial numbness

Worst case is anesthesia dolorosa

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TRIGEMINAL NEURALGIA Percutaneous Trigeminal Rhizotomy

– Needle inserted through cheek one inch from angle of the mouth– Needle advanced through foramen ovale using fluoroscopy

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TRIGEMINAL NEURALGIA Percutaneous Trigeminal Rhizotomy Via

– Radiofrequency Ablation (heat) 6205 patients Stimulation is performed prior to ablation to ensure correct target Only selective technique If V1 involved, caution to not over-numb corneal sensation, which risks

keratophathy Highest rates of initial pain relief and the lowest rates of pain recurrence

– Glycerol (chemical) 1217 patients CSF coming from needle is a good finding before bathing nerve Highest recurrence rate

– Balloon (mechanical) 759 patients More likely to affect mastication

1. Taha JM, Tew JM Jr. Comparison of surgical treatments for trigeminal neuralgia: reevaluation of radiofrequency rhizotomy. Neurosurgery. 1996 May;38(5):865-71.

2. Scrivani SJ, Mathews ES, Maciewicz R: Trigeminal Neuralgia. In Mehta N, Maloney GE, Bana D, Scrivani SJ (eds): Head, Face and Neck Pain: Science, Evaluation and Management. 1st ed., John Wiley & Sons, Inc., Hoboken, NJ, 465-510, 2009.

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TRIGEMINAL NEURALGIA Stereotactic Radiosurgery

– Used for treatment of tumors, vascular lesions, and functional disorders like TN– Highly focused beams of ionizing radiation with high precision– Useful for targets that are inaccessible for open surgery – Immediately outside of target there is a steep drop in radiation so surrounding

tissues are relatively spared Not useful for large targets

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TRIGEMINAL NEURALGIA Stereotactic Radiosurgery

– 497 patients presenting with TN underwent GKS No clear vascular compression or history of multiple sclerosis Results 169 patients became pain free within the first 48 hour

Pain recurrence in 66 patients (39%) Postoperative hypesthesia in 18 patients (13.7%)

194 patients became pain free within post treatment Day 3-30 Pain recurrence in 71 patients (36.6%) Postoperative hypesthesia in 30 patients (19%)

91 patients became pain free 30 days post-GKS Pain recurrence in 27 patients (29.7%) Postoperative hypesthesia in 22 patients (30.6%)

1. Tuleasca C, Carron R, et al. Patterns of pain-free response in 497 cases of classic trigeminal neuralgia treated with Gamma Knife surgery and followed up for least 1 year. J Neurosurg. 2012 Dec;117 Suppl:181-8.

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CONCLUSIONS OF PHN, PHI, TN There are many treatments for these 3 conditions

Medication trials should start at a low dose, and titrations should be fast/slow based on patient preference and side effects

Combination therapies should be considered

Do not hesitate to refer patients to another provider for treatments that you may not provide

With so many treatment options, there is little reason for our patients to not have their pain addressed

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THANK YOU!!!

JOHN R. GRAHAM HEADACHE CENTER

FELLOWS AND STAFF

2015-2016

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Post Herpetic Neuralgia, Post Herpetic Itch & Trigeminal ... Herpetic Nerua… · the treatment of post herpetic neuralgia, post herpetic itch, and trigeminal neuralgia. VARICELLA