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Trigeminal neuralgia, facial pain in MS 
Prof Joanna Zakrzewska 
Head of facial pain unit 
Eastman Dental Hospital
Aims and Objectives 
Differential diagnosis 
Trigeminal neuralgia 
Diagnosis 
Investigations 
Medical management 
Surgical management 
Epidemiology 
Patho-physiology
Epidemiology TN 
Incidence : 4.5 / 100,000 
Prevalence : 0.001% - 0.3% 
Peak incidence : 50-60 years 
Multiple sclerosis (2- 4 % of TN 
patients) 
Hypertension 
Stroke 
Zakrzewska JM, Hamlyn PJ. In Epidemiology of 
Pain. IASP, 1999 
Mueller D et al Cephalagia 2011 
Pan et al Cephalagia 2011
Changing epidemiology of TN? 
Incidence 
per 100,000 
PY 
Hall et al 
2006 
Dieleman 
2008 
Koopman et 
al 2009 
Number 8,268 
322 118 
Incidence 26.8 
28.9 12.6
What are other causes of 
unilateral episodic facial pain?
Drangsholt et al 2001
Dental causes of pain
Dental Pain – acute/ chronic
Chronic continuous pain 
Yes No 
Unilateral continuous orofacial pain 
Yes No 
• Post herpetic 
neuralgia 
• Post traumatic 
trigeminal pain 
• Anesthesia 
dolorosa 
• Persistent 
dentoalveolar 
pain 
• Referred pain 
• Temporomandibular 
disorders** 
• Persistent orofacial 
muscle pain ** 
Unilateral episodic orofacial pain 
Yes No 
• Trigeminal 
neuralgia 
classical (type 1) 
• Trigeminal 
neuralgia 
symptomatic 
• Trigeminal 
neuralgia + 
concomitant pain 
( type 2) 
• Glossopharyngeal 
neuralgia 
• Tension type 
headache 
• Medication 
overuse 
headache 
• Post stroke pain 
• Giant cell arteritis * 
Cancer pain 
Burning mouth 
syndrome 
Chronic migraine 
• Trigeminal autonomic 
cephalagias 
• Episodic migraine * 
Persistent idiopathic facial 
pain 
Zakrzewska BJA 2013
Temporomandibular Disorders 
musculoskeletal 
© Zakrzewska
TMD 
© Zakrzewska
Education- explanation 
© Zakrzewska
Education vs splint 
Michelotti JADA 2012;143:47-53 © Zakrzewska
TMD management 
Reassurance, education, 
relaxation, behaviour 
changes, intermittent 
NSAID 
Physiotherapy/ 
acupuncture, pain coping 
strategies, reinforce self 
care, address 
psychological distress 
Tricyclic antidepressants, 
cognitive behaviour 
therapy, reinforce self 
care 
© Zakrzewska
Why is the right diagnosis important? 
• Epidemiological studies 
• Genetic studies 
• Recruiting into clinical trials 
• Appropriate managements and referrals 
• Variants may involve different 
mechanisms 
© Zakrzewska
Who makes the diagnosis? 
HCP making 
diagnosis 
TN 
5287 
ATN 
189 
OFP 
857 
General medical 
practitioner % 36 36 18 
Neurologist % 29 30 17 
Dentist % 20 15 10 
Other specialists % 15 19 55
Listen to your patient he is 
telling you the diagnosis
The Story of Pain 
curiosity to ask “tell me about yourself” 
patience to wait for the answer 
Platt et al 2001
Stories 
• patients tell stories to become who they are 
• patient stories are addressed to someone 
• the clinician must listen 
• the quality of attention is important and 
you " have to be caught up” – it is an act of 
surrender
What are the features of 
trigeminal neuralgia? 
Misery by Rosa Sepple
Character of TN pain 
The character of trigeminal neuralgia is very 
distinctive and pts will use words such electric 
shock, lightening – implies speed as well as severity
© Zakrzewska 
Duration 
 paroxysmal 
 pain of abrupt onset and termination 
 refractory intervals 
 no background pain 
memorable first attack
Temporal features 
Classical TN TN – Type 2, concomitant pain 
© Zakrzewska 
Refractory period
Periodicity of TN
Site and Radiation 
Rare
Provoking factors 
© Zakrzewska 
R Conelly 
Evoked vs spontaneous
Trigeminal Neuralgia –IASP 
“ a sudden, usually unilateral, 
severe, brief, stabbing, recurrent 
pain in the distribution of one or 
more branches of the fifth cranial 
nerve”.
How does TN affect quality of life ? 
© Zakrzewska 
© R. Sepple
Associated features 
Loneliness – isolation – how can 
you go to social activities when 
you cannot eat, 
how can you be intimate when 
you cannot bear your face to be 
touched 
How do you get across the 
message that despite looking 
normal you have one of the most 
suicide pain 
Depression is common 
Fear of a returning attack is 
always with the patients and 
psychologist will tell us that this 
drives further pain
Fear 
©Eastman
Tolle et al 
Pain Practice 2006
The Patient’s Journey 
Through Trigeminal Neuralgia 
Zakrzewska Padfield May 2014
Trigeminal Neuralgia 
Limonadi et al 2006, Obermann et al 2007
What is the diagnosis of this 
patient ?
Symptomatic TN 
Trigeminal 
nerve 
Tumour 
© Zakrzewska
TG 
MS plaque
vessel 
nerve 
Neurovascular compression
Aetiology / Pathophysiology
Nerve Structure 
© Zakrzewska
Root entry zone, change in nerve 
structure
Love and Coakham, Brain 2001: 124, 2347 – 2360
Management
Outcomes 
% pain Therapy 
relief 
Decreased 
intensity 
frequency 
Character of pain 
Provoking factors 
Side 
effects 
Beliefs 
concerns 
Objective 
measures 
Health utilisation 
© Zakrzewska
Medical management
Systematic reviews guidelines 
www.aan.com
Which have been evaluated in 
Randomised controlled trials - RCTs? 
carbamazepine baclofen 
clonazepam 
epanutin valproate lamotrigine
Which have been evaluated in RCTs? 
gabapentin 
oxcarbazepine pregabalin 
sumatriptan 
leviteracetam 
Dextromethorphan 
Topiramate 
Botox
Carbamazepine 
3 RCT studies (total 160 patients) 
NNT 1.7 for >50% pain relief 
Maximum 2.4 g / day 
Usual dose 200-1,200 mg 
NNH 2.6 
Multiple drug interactions
Carbamazepine adverse events 
osteoporosis 
© Zakrzewska
Oxcarbazepine 
Starting 300 mg bd 
Dose range 600-1,200 mg /day 
Maximum 2,400 mg/day 
Hyponatraemia higher doses 
Few drug interactions
Side effects to anticonvulsants
Acute management 
 Fosphenytoin infusion 
 Sumatriptan 3mg sc 
24 patients in RCT 
12/24 improved for mean 8 hours 
 Lidocaine 
Injection 
Intranasal 
IV 
Cheshire Fosphenytoin J Pain Sympt 2001 
Kania Sumatriptan Head 2006 
Han Lidocaine Clin Prac 2008, Kania Br J Aneasth 2006
Results of RCTs in TN 
carbamazepine 
oxcarbazepine 
lamotrigine 
baclofen 
gabapentin + LA 
pimozide = 
tizanidine ? 
tocainide 
dextromethorphan ? 
topiramate ?
AAN/ EFNS Guideline
New drug for TN
Novel Sodium Channel Blocker 
CNV1014802 June 2014 
• Treatment failure rate 
33% CNV1014802 vs 65% placebo 
• Decrease in pain severity 
55% CNV1014802 vs 18% placebo 
• Average reduction in number of paroxysms 
60% CNV1014802 vs 12% placebo
Medications 
There is a medicine 
you can take 
But it’s not the cure 
It may make your 
drowsy 
It may make you sick 
There are more pills 
to take 
And there’s no 
miracle fix
Response to medication
Insufficient evidence to say 
when surgery should be offered 
Patients should be given details of all 
surgical procedures
Systematic review surgery 
Cochrane Database of Systematic 
Reviews 2011, Issue 9 
3 studies 
2 radiofrequency 
thermocoagulation 
comparing techniques 
1 stereotactic surgery 
comparing dosages 
Grading
Gasserian Ganglion procedures 
Radiofrequency 
rhizotomy 
Glycerol rhizotomy 
Balloon compression
Microvascular 
decompression 
Partial sensory 
rhizotomy 
Posterior fossa 
Zakrzewska Coakham 
Current Neurol 2012
Posterior fossa 
Trigeminal nerve 
compressed by 
superior cerebellar 
artery 
© Prof H Coakham
Gamma knife 
Radiation doses of 90- 70Gy 
Non invasive ablative 
procedure
Complete pain relief after surgery 
100 
90 
80 
70 
60 
50 
40 
30 
20 
10 
0 
0 1 2 3 4 5 
years 
% probability 
radiofrequency thermocoagulation percutaneous glycerol rhizotomy 
microvascular decompression gamma knife 
© Zakrzewska
Complications 
Mortality 
0.2 - 0.5 % for MVD 
data from 14 studies in 2785 patients 
© Zakrzewska
Complications 
Peripheral 
ganglion 
lesions 
© Zakrzewska
Complications 
© Zakrzewska
How 302 patients with MS and TN 
compare with 7982 TN only patients ? 
Same age and demographics 
More constant, bilateral pain 
Use wider range of drugs 
Undergo more ablative surgery
Why are there few TN Drug Trials ? 
Diagnosis strictly clinical 
Condition relatively rare 
Medications may interfere with other drugs 
Medications may take time to work 
Spontaneous remission common 
Side-effects may take time to appear 
Pain very severe: justify using placebo
AAN/EFNS guidelines
Patient Information 
© Zakrzewska
Support groups 
US , UK, Australia , Canada 
Web sites : http://www.tna-support.org/ 
http://www.tna.org.uk/ 
© Zakrzewska
Drug therapy 
Microvascular 
decompression 
MS 
Drug 
therapy 
Neurovascular 
compression 
Tumours etc 
Idiopathic TN 
MRI 
Blood tests 
Symptomatic TN 
Ablative procedures Gasserian 
ganglion 
Gamma knife 
Trigeminal neuralgia 
Primary care 
Carbamazepine 
Initial good control but now failing 
Refer pain clinic 
Neurology headache 
Neurosurgery 
Carbamazepine 
Oxcarbazepine 
Lamotrigine 
Baclofen 
Pregablin 
Gabapetin 
Poor 
quality of 
life 
Joint neurosurgery 
clinic 
Psychology 
© Zakrzewska
Choice, Option, Decision 
http://www.advancingqualityalliance.nhs.uk/SDM
References / further 
reading
TN Review BMJ 2014
Guideline website 
www.aan.com
Resources – e-learning
TMD & trigeminal neuralgia 
http://cks.nice.org.uk/trigeminal-neuralgia 
http://cks.nice.org.uk/tmj-disorders
Educational material 
http://www.efic.org/ 
Year against orofacial pain
Summary 
• Epidemiology provides 
clues to aetiology 
• Differential diagnosis 
• Important diagnostic 
features of TN 
• Causes 
• Investigations 
• Management 
• References 
@ R.Sepple
Thank you 
Face to face Rosa Sepple

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Trigeminal neuralgia, facial pain in MS

  • 1. Trigeminal neuralgia, facial pain in MS Prof Joanna Zakrzewska Head of facial pain unit Eastman Dental Hospital
  • 2. Aims and Objectives Differential diagnosis Trigeminal neuralgia Diagnosis Investigations Medical management Surgical management Epidemiology Patho-physiology
  • 3. Epidemiology TN Incidence : 4.5 / 100,000 Prevalence : 0.001% - 0.3% Peak incidence : 50-60 years Multiple sclerosis (2- 4 % of TN patients) Hypertension Stroke Zakrzewska JM, Hamlyn PJ. In Epidemiology of Pain. IASP, 1999 Mueller D et al Cephalagia 2011 Pan et al Cephalagia 2011
  • 4. Changing epidemiology of TN? Incidence per 100,000 PY Hall et al 2006 Dieleman 2008 Koopman et al 2009 Number 8,268 322 118 Incidence 26.8 28.9 12.6
  • 5. What are other causes of unilateral episodic facial pain?
  • 8. Dental Pain – acute/ chronic
  • 9. Chronic continuous pain Yes No Unilateral continuous orofacial pain Yes No • Post herpetic neuralgia • Post traumatic trigeminal pain • Anesthesia dolorosa • Persistent dentoalveolar pain • Referred pain • Temporomandibular disorders** • Persistent orofacial muscle pain ** Unilateral episodic orofacial pain Yes No • Trigeminal neuralgia classical (type 1) • Trigeminal neuralgia symptomatic • Trigeminal neuralgia + concomitant pain ( type 2) • Glossopharyngeal neuralgia • Tension type headache • Medication overuse headache • Post stroke pain • Giant cell arteritis * Cancer pain Burning mouth syndrome Chronic migraine • Trigeminal autonomic cephalagias • Episodic migraine * Persistent idiopathic facial pain Zakrzewska BJA 2013
  • 13. Education vs splint Michelotti JADA 2012;143:47-53 © Zakrzewska
  • 14. TMD management Reassurance, education, relaxation, behaviour changes, intermittent NSAID Physiotherapy/ acupuncture, pain coping strategies, reinforce self care, address psychological distress Tricyclic antidepressants, cognitive behaviour therapy, reinforce self care © Zakrzewska
  • 15. Why is the right diagnosis important? • Epidemiological studies • Genetic studies • Recruiting into clinical trials • Appropriate managements and referrals • Variants may involve different mechanisms © Zakrzewska
  • 16. Who makes the diagnosis? HCP making diagnosis TN 5287 ATN 189 OFP 857 General medical practitioner % 36 36 18 Neurologist % 29 30 17 Dentist % 20 15 10 Other specialists % 15 19 55
  • 17. Listen to your patient he is telling you the diagnosis
  • 18. The Story of Pain curiosity to ask “tell me about yourself” patience to wait for the answer Platt et al 2001
  • 19. Stories • patients tell stories to become who they are • patient stories are addressed to someone • the clinician must listen • the quality of attention is important and you " have to be caught up” – it is an act of surrender
  • 20. What are the features of trigeminal neuralgia? Misery by Rosa Sepple
  • 21. Character of TN pain The character of trigeminal neuralgia is very distinctive and pts will use words such electric shock, lightening – implies speed as well as severity
  • 22. © Zakrzewska Duration  paroxysmal  pain of abrupt onset and termination  refractory intervals  no background pain memorable first attack
  • 23. Temporal features Classical TN TN – Type 2, concomitant pain © Zakrzewska Refractory period
  • 26. Provoking factors © Zakrzewska R Conelly Evoked vs spontaneous
  • 27. Trigeminal Neuralgia –IASP “ a sudden, usually unilateral, severe, brief, stabbing, recurrent pain in the distribution of one or more branches of the fifth cranial nerve”.
  • 28. How does TN affect quality of life ? © Zakrzewska © R. Sepple
  • 29. Associated features Loneliness – isolation – how can you go to social activities when you cannot eat, how can you be intimate when you cannot bear your face to be touched How do you get across the message that despite looking normal you have one of the most suicide pain Depression is common Fear of a returning attack is always with the patients and psychologist will tell us that this drives further pain
  • 31. Tolle et al Pain Practice 2006
  • 32. The Patient’s Journey Through Trigeminal Neuralgia Zakrzewska Padfield May 2014
  • 33. Trigeminal Neuralgia Limonadi et al 2006, Obermann et al 2007
  • 34. What is the diagnosis of this patient ?
  • 35. Symptomatic TN Trigeminal nerve Tumour © Zakrzewska
  • 39. Nerve Structure © Zakrzewska
  • 40. Root entry zone, change in nerve structure
  • 41.
  • 42. Love and Coakham, Brain 2001: 124, 2347 – 2360
  • 44. Outcomes % pain Therapy relief Decreased intensity frequency Character of pain Provoking factors Side effects Beliefs concerns Objective measures Health utilisation © Zakrzewska
  • 47.
  • 48. Which have been evaluated in Randomised controlled trials - RCTs? carbamazepine baclofen clonazepam epanutin valproate lamotrigine
  • 49. Which have been evaluated in RCTs? gabapentin oxcarbazepine pregabalin sumatriptan leviteracetam Dextromethorphan Topiramate Botox
  • 50. Carbamazepine 3 RCT studies (total 160 patients) NNT 1.7 for >50% pain relief Maximum 2.4 g / day Usual dose 200-1,200 mg NNH 2.6 Multiple drug interactions
  • 51. Carbamazepine adverse events osteoporosis © Zakrzewska
  • 52. Oxcarbazepine Starting 300 mg bd Dose range 600-1,200 mg /day Maximum 2,400 mg/day Hyponatraemia higher doses Few drug interactions
  • 53. Side effects to anticonvulsants
  • 54. Acute management  Fosphenytoin infusion  Sumatriptan 3mg sc 24 patients in RCT 12/24 improved for mean 8 hours  Lidocaine Injection Intranasal IV Cheshire Fosphenytoin J Pain Sympt 2001 Kania Sumatriptan Head 2006 Han Lidocaine Clin Prac 2008, Kania Br J Aneasth 2006
  • 55. Results of RCTs in TN carbamazepine oxcarbazepine lamotrigine baclofen gabapentin + LA pimozide = tizanidine ? tocainide dextromethorphan ? topiramate ?
  • 58. Novel Sodium Channel Blocker CNV1014802 June 2014 • Treatment failure rate 33% CNV1014802 vs 65% placebo • Decrease in pain severity 55% CNV1014802 vs 18% placebo • Average reduction in number of paroxysms 60% CNV1014802 vs 12% placebo
  • 59. Medications There is a medicine you can take But it’s not the cure It may make your drowsy It may make you sick There are more pills to take And there’s no miracle fix
  • 60.
  • 62. Insufficient evidence to say when surgery should be offered Patients should be given details of all surgical procedures
  • 63. Systematic review surgery Cochrane Database of Systematic Reviews 2011, Issue 9 3 studies 2 radiofrequency thermocoagulation comparing techniques 1 stereotactic surgery comparing dosages Grading
  • 64. Gasserian Ganglion procedures Radiofrequency rhizotomy Glycerol rhizotomy Balloon compression
  • 65. Microvascular decompression Partial sensory rhizotomy Posterior fossa Zakrzewska Coakham Current Neurol 2012
  • 66. Posterior fossa Trigeminal nerve compressed by superior cerebellar artery © Prof H Coakham
  • 67. Gamma knife Radiation doses of 90- 70Gy Non invasive ablative procedure
  • 68. Complete pain relief after surgery 100 90 80 70 60 50 40 30 20 10 0 0 1 2 3 4 5 years % probability radiofrequency thermocoagulation percutaneous glycerol rhizotomy microvascular decompression gamma knife © Zakrzewska
  • 69. Complications Mortality 0.2 - 0.5 % for MVD data from 14 studies in 2785 patients © Zakrzewska
  • 70. Complications Peripheral ganglion lesions © Zakrzewska
  • 72. How 302 patients with MS and TN compare with 7982 TN only patients ? Same age and demographics More constant, bilateral pain Use wider range of drugs Undergo more ablative surgery
  • 73. Why are there few TN Drug Trials ? Diagnosis strictly clinical Condition relatively rare Medications may interfere with other drugs Medications may take time to work Spontaneous remission common Side-effects may take time to appear Pain very severe: justify using placebo
  • 76. Support groups US , UK, Australia , Canada Web sites : http://www.tna-support.org/ http://www.tna.org.uk/ © Zakrzewska
  • 77.
  • 78. Drug therapy Microvascular decompression MS Drug therapy Neurovascular compression Tumours etc Idiopathic TN MRI Blood tests Symptomatic TN Ablative procedures Gasserian ganglion Gamma knife Trigeminal neuralgia Primary care Carbamazepine Initial good control but now failing Refer pain clinic Neurology headache Neurosurgery Carbamazepine Oxcarbazepine Lamotrigine Baclofen Pregablin Gabapetin Poor quality of life Joint neurosurgery clinic Psychology © Zakrzewska
  • 79. Choice, Option, Decision http://www.advancingqualityalliance.nhs.uk/SDM
  • 83.
  • 85. TMD & trigeminal neuralgia http://cks.nice.org.uk/trigeminal-neuralgia http://cks.nice.org.uk/tmj-disorders
  • 86. Educational material http://www.efic.org/ Year against orofacial pain
  • 87. Summary • Epidemiology provides clues to aetiology • Differential diagnosis • Important diagnostic features of TN • Causes • Investigations • Management • References @ R.Sepple
  • 88. Thank you Face to face Rosa Sepple