1. Professor of Neurology
Tension Type Headache
Rob Cowan, MD, FAHS, FAAN
Professor of Neurology
Stanford University
USA

2. Disclosures
I have no disclosures relevant to this presentation other than consulting for Tonix Pharmaceuticals which is developing a novel isomer of Isometheptine for the treatment of Tension-type Headache

3. Objectives
To present the current ICHD 3 (beta)diagnostic criteria for Tension-type Headache
To review the current understanding of the pathophysiology of Tension-type Headache
To discuss the differential diagnosis, work-up and management of Tension-type Headache

4. Previously used terms:
Tension headache
muscle contraction headache
Psychomyogenic headache
Stress headache
Ordinary headache
Essential headache
Idiopathic headache
Psychogenic headache

5. ICHD 3 (beta)Diagnostic criteria
2. Tension-type headache (TTH)
2.1 Infrequent episodic tension-type headache
2.1.1 Infrequent episodic tension-type headache associated with pericranial tenderness
2.1.2 Infrequent episodic tension-type headache not associated with pericranial tenderness
2.2 Frequent episodic tension-type headache
2.2.1 Frequent episodic tension-type headache associated with pericranial tenderness
2.2.2 Frequent episodic tension-type headache not associated with pericranial tenderness
2.3 Chronic tension-type headache
2.3.1 Chronic tension-type headache associated with pericranial tenderness
2.3.2 Chronic tension-type headache not associated with pericranial tenderness
2.4 Probable tension-type headache
2.4.1 Probable infrequent episodic tension-type headache
2.4.2 Probable frequent episodic tension-type headache
2.4.3 Probable chronic tension-type headache

6. Abbreviations TTH = Tension-type Headache (of any type)
ETTH = Episodic Tension-type Headache
CTH = Chronic Tension-type Headache
CDH = Chronic Daily Headache (of any type)
CM = Chronic Migraine
ICHD = International Classification of Headache Disorders

7. Introduction - History
Previously considered to be primarily psychogenic, studies strongly suggest a neurobiological basis, at least for the more severe subtypes of tension-type headache.
The division of Tension-type headache into episodic and chronic subtypes, introduced in ICHD-I, has proved extremely useful.
Infrequent episodic tension-type headache, which occurs in almost the entire population, usually has very little impact on the individual and, in most instances, requires no attention from the medical profession.
Frequent episodic tension-type headache can be associated with considerable disability, and sometimes warrants treatment with expensive drugs.
Chronic tension-type headache is a serious disease, causing greatly decreased quality of life and high disability.

8. Introduction - Pathogenesis
Multifactorial
Peripheral Mechanisms
Myofascial nociception
Predominates in Episodic Tension-type Headache
Central Mechanisms
Sensitization and inadequate endogenous pain control
Predominates in Chronic Tension-type Headache

9. Primary or secondary headache or both?
Tension-type headache can exist in isolation as a primary headache
The existence of identifiable trigger(s) does not make the headache secondary
Tension-type headache can co-exist with another primary headache (such as migraine)
Tension-type headache can co-exist with another secondary headache (such as Giant Cell Arteritis or Post-traumatic headache

10. Epidemiology TTHLifetime prevalence 79% (3% CTTH)
1 year prevalence (age 40) = 48.2%
1 year prevalence (age 26) = 11.1%
Mean life time prevalence is 46%
Higher in women 4:5) and declines with age
Prevalence increases with educational level
Can occur in children
Li S, et al. The global burden of headache: a documentation of headache prevalence and disability worldwide. Cephalalgia 2007;27:

11. Causes The exact mechanisms of Tension-type headache are not known.
Peripheral pain mechanisms most likely play a role in Infrequent and Frequent episodic tension-type headache.
Central pain mechanisms play a more important role in Chronic tension-type headache
Increased pericranial tenderness recorded by manual palpation is the most significant abnormal finding in patients with tension-type headache.
The tenderness is typically present interictally, increased during actual headache and increases with the intensity and frequency of headaches.
Pericranial tenderness is recorded by manual palpation by small rotating movements and a firm pressure with the second and third fingers on the frontal, temporal, masseter, pterygoid, sternocleidomastoid, splenius and trapezius muscles.

12. TTH and Muscle Tension?
Overall electromyographic activity is greater in CTTH than in controls, but not in individual muscles.
Onobotulinum toxin decreases temporalis EMG readings but does not affect TTH
Lactate levels in trapezius not different in TTH than in controls.
No inflammatory changes in muscles in CTTH
Ashina M, et al. Tender points are not sites of ongoing inflammation- in vivo evidence in patients with chronic tension-type headache. Cephalalgia 2003;23:109-16

13. Pericranial Tenderness in TTH?
Pericranial Tenderness is greater interictally in patients with TTH
Physical therapy improves neck mobility and anterocollis without any effect on TTH outcomes
Pain thresholds and pericranial tenderness are abnormal in CTTH but not in ETTH
Bendtsen L, et al. Decreased pain detection and tolerance thresholds in chronic tension-type headache. Arch Neurol 1996;53:373-6

14. Are ETTH and CTTH separate diseases?
Nociceptive reflexes are normal in ETTH and abnormal in CTTH (measured with painful stimulus to trigeminal region)
Pharmacologic modulation of temporalis exteroceptors blunts silent period (ES2) in CTTH, suggesting serotonergic inhibition.
May explain why Amitriptyline works only in CTTH
Biceps Femoris flexion reflex and Laser-evoked nociceptive potentials are abnormal in CTTH
deTommaso M, et al. Heat pain thresholds and cerebral event0related potentials following painful CO2laser stimulation in chronic tension-type headache. Pain 2003;104:111-19

15. Structural Brain Changes in TTH
fMRI shows DECREASED brain tissue mass in pain matrices in CTTH
Changes are similar to that seen in low back pain and phantom limb pain
These changes contrast with the INCREASED density seen in migraine.
Schmidt-Wilcke T, et al: Gray matter decrease in patients with chronic tension-type headache. Neurology 2005;65:1483-6

16. Neuropeptides in TTH
Glyceryl trinitrate induces TTH in patients with TTH as it induces Migraine in patients with Migraine! Suggests central sensitization to nitric oxide.
CGRP levels are not affected in TTH (but in CTTH with migrainous features, they are) Neither are Substance P or neuropeptide Y.
Serotonin data is very mixed and not consistent with finding in Migraine.

17. Genetics of TTH Risk of TTH same as general population in twin studies
High frequency ETTH and CTTH show greater risk in twin studies.
Genetic data is sparse
Russell MB, Genetics of Tension-type headache. The J Headache and Pain Apr :8(2): 71-6

18. Model of TTH Pathogenesis
After Fumal A, Schoenen J. Tension-type headache: current research and clinical management. Lancet Neurology. 2008;7(1) 70-83

19. Migraine or Tension-type?
Spectrum Study: 71% of patients who were initially diagnosed with TTH had their diagnosis changed to Migraine after chart review.
Lipton RB, et al. Diagnostic lessons from the spectrum study. Neurology 2002; 58:S27-31

20. Challenges to Diagnosis
Parameter
Migraine
Tension-type
Frequency
Variable
Duration*
4-72 hours**
30 min-7 days
Location
Unilat (40% bilat)
Bilateral
Description
Pulsating (50% non-pulsating)
Pressing/tighten-
ing (non pulsate)
Intensity
Moderate-Severe
Mild-Moderate
Effect of activity
Aggravates
Does not aggravate
Nausea or Vomit
Yes No
Photo/Phonophobia
One or both
None or one only
Attribution
None
Discrimination between tension-type headache and mild migraine without aura.
Patients with frequent headaches often suffer from both disorders
*untreated or unsuccessfully treated
** 2-72 hours in children
ICHD-3 (beta) Cephalalgia 2013; 33:

21. Differential diagnosis
Migraine – in chronic form characteristic features disappear and pain is less severe
Cervical Cephalgia– muscle tenderness of tension type headache may involve the neck
Medication overuse headache – consider in patients taking opioid or combination analgesics for an average of 10 days/month
New Daily Persistent Headache – abrupt onset, check for precipitating event

22. Infrequent episodic tension-type headache
typically bilateral
pressing or tightening in quality
mild to moderate intensity
lasting 30 minutes to 7 days
not worsened with routine physical activity
not associated with nausea
photo or phonophobia may be present.

23. Formal Diagnostic Criteria:
A. At least 10 episodes of headache occurring on <1 day per month on average (<12 days per year) and fulfilling criteria B-D
B. Lasting from 30 minutes to 7 days
C. At least two of the following four characteristics:
1. bilateral location
2. pressing or tightening (non-pulsating) quality
3. mild or moderate intensity
4. not aggravated by routine physical activity such as walking or climbing stairs
D. Both of the following:
1. no nausea or vomiting
2. no more than one of photophobia or phonophobia
E. Not better accounted for by another ICHD-3 diagnosis.

24. Infrequent episodic tension-type headache and pericranial tenderness
A. Episodes fulfilling criteria for 2.1 Infrequent episodic tension-type headache
B. Increased pericranial tenderness on manual palpation. OR
B. No increase in pericranial tenderness.

25. Frequent episodic tension-type headache
Frequent episodes of headache
typically bilateral
pressing or tightening in quality
mild to moderate intensity
pain not worsened by routine physical activity
not associated with nausea,
photo or phonophobia may be present.

26. Formal Diagnostic criteria:
A. At least 10 episodes of headache occurring on 1-14 days per month on average for >3 months (12 and <180 days per year) and fulfilling criteria B-D
B. Lasting from 30 minutes to 7 days
C. At least two of the following four characteristics:
1. bilateral location
2. pressing or tightening (non-pulsating) quality
3. mild or moderate intensity
4. not aggravated by routine physical activity such as walking or climbing stairs
D. Both of the following:
1. no nausea or vomiting
2. no more than one of photophobia or phonophobia
E. Not better accounted for by another ICHD-3 diagnosis.

27. Comments
Frequent episodic tension-type headache often coexists with 1.1 Migraine without aura.
Coexisting tension-type headache in migraineurs should preferably be identified through use of a diagnostic headache diary.
The treatment of migraine differs considerably from that of tension-type headache.
It is important to distinguish between these headache types in order to select the right treatment for each while avoiding medication overuse.

28. 2.3 Chronic tension-type headache
A disorder evolving from frequent episodic tension-type headache, with daily or very frequent episodes of headache
typically bilateral
pressing or tightening in quality
mild to moderate intensity
lasting hours to days, or unremitting
pain does not worsen with physical activity
may be associated with mild nausea, photo or phonophobia.

29. Diagnostic criteria:
A. Headache occurring on 15 days per month on average for >3 months (180 days per year), fulfilling criteria B-D
B. Lasting hours to days, or unremitting
C. At least two of the following four characteristics:
1. bilateral location
2. pressing or tightening (non-pulsating) quality
3. mild or moderate intensity
4. not aggravated by routine physical activity such as walking or climbing stairs
D. Both of the following:
1. no more than one of photophobia, phonophobiaor mild nausea
2. neither moderate or severe nausea nor vomiting
E. Not better accounted for by another ICHD-3 diagnosis.

30. Comments:
Chronic tension-type headache evolves over time from Frequent episodic tension-type headache
When these criteria are fulfilled by headache that, unambiguously, is daily and unremitting from less than 24 hours after its first onset, code as New daily persistent headache.
Chronic tension-type headache, headache on at least 15 days must meet the criteria for Tension-type headache
Chronic tension-type headache with migraine headache on at least 8 days meets the criteria for Chronic Migraine. Therefore, a patient can fulfill criteria for both these diagnosesby having headache on 25 days per month meeting migraine criteria on 8 days and tension-type headache criteria on 17 days. In these cases, only the diagnosis Chronic migraine should be given.

31. Chronic Tension-type headache and medication overuse
In cases in which there is overuse of medication and the criteria for Chronic tension-type headache are also fulfilled, the rule is to code for both Chronic tension-type headache and Medication-overuse headache .
After drug withdrawal, the diagnosis should be re-evaluated: not uncommonly the criteria for Chronic tension-type headache will no longer be fulfilled, with reversion to one or other episodic subtype.

32. Probable tension-type headache
Tension-type-like headache missing one of the features required to fulfill all criteria for a subtype of tension-type headache, and not fulfilling criteria for another headache disorder.

33. Clinical Presentation
May be episodic or chronic on presentation
Constitutional or neurological symptoms are uncommon
Detailed history
Natural history
Exacerbating/alleviating factors
Comorbidities

34. Examination and investigation
Head and Neck (ROM, auscultation, posture)
Neurological examination
Manual palpation of pericranial muscles ( frontal, temporal, masseter, pterygoid, sternomastoid, splenius and trapezius.
Fundoscopy for papilledema
Lab work and Testing
If neuro examination normal none needed

35. Imaging Neuroimaging should be arranged if
Atypical pattern of headache
History of seizures
Neurological signs or symptoms
Symptomatic illness
Immunocompromise

36. Acute Treatment Infrequent headache
Good results from non prescription medication
May need reassurance
Always consider non-pharmacologic options
Monitor for medication overuse
Rosen NL, Psychological issues in the evaluation and treatment of tension-type headache. Curr Pain Headache Rep Dec, 16(6):545-53

37. Acute Pharmacologic Treatment
Simple analgesia
Aspirin 500 – 1000mg
NSAIDS
Paracetamol less effective than NSAIDS
Combination drugs helpful – watch for medication overuse
Opioids or sedatives should not be used
Steiner TJ, Voelker M. Gastrointestinal tolerability of aspirin and the choice of over-the-counter analgesia for short-lasting acute pain. J Clin Pharm Ther APR,34(2):177-86
Diener HC at al. Use of a fixed combination of actylsalicylic acid, acetaminophen and caffeine compared with acetaminophen alone in episodic tension-type headache: meta-analysis of four randomized double-blind placebo-controlled, crossover studies. J Headache Pain 2014 Nov 19;15;76

38. Preventive Treatment
Consider when headaches are frequent or acute attacks don’t respond to abortive treatment
Best evidence is for Amitriptyline mg/day. It helps both pain and muscle tenderness. Works best when started at low dose and increased weekly
Mirtazipine 15-30mg/day
Unhelpful
SSRI’s
Botulinium toxin
Banzi R, et al. Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors for the prevention of tension-type headache in adults. Cochrane Database Syst Rev 2015 May 1;5CD)11681

39. Preventive Treatment Should be considered when:
diary or patient report indicates increasing frequency of headache days/mo.
there is evidence of medication overuse
headaches are significantly interfering with patient’s quality of life

40. Non-pharmacologic Treatment
Education, lifestyle and non-pharmacological treatment
Education, reassurance
Lifestyle modification (sleep, exercise, eating)
Cognitive and Behavioral therapies
Orr SL. Diet and nutraceutical interventions for headache management: A review of the evidence Cephalalgia Jun 11.
Christiansen S et al. Outpatient combined group and individual cognitive-behavioral treatment for patient with migraine and tension-type headache in a routine clinical setting. Headache Sep:55(8):

41. Treatment Summary
After Fumal A, Schoenen J. Tension-type headache: current research and clinical management. Lancet Neurology. 2008;7(1) 70-83

42. Advanced Treatment Refer to Specialist when:
Diagnosis is unclear or complex
Patient does not respond to treatment
Complicated by medication overuse
Local resources and facilities are not adequate

43. Prognosis
Remission from Chronic to Episodic form range from 30 to 67%.
25% of patients with Episodic will carry progress to Chronic
15 to 31% will remain Chronic
21% develop medication overuse
Crystal SC, Robbins MS. Epidemiology of tension-type headache. Current Pain and Headache Rep Dec 2010, 14(6);

44. Poor prognosis Chronic headache at presentation
Co-existing migraine, TMD, Depression, Anxiety,
Medication Overuse
Not being married
Sleep problems
Other Pain Syndromes

45. Good prognosis Onset of Older age
Episodic tension type headache at baseline
No co-existent pain syndromes
Obesity
Wang Y, et al. The prevalence of primary headache disorders and their associated factors among nursing staff in North China. J Headache Pain 2015 Jan13,16:4

46. Conclusions
TTH is a clinically and pathophysiologically heterogeneous entity.
Misdiagnosis is common in particular among those suffering from mild migraine
Pericranial myofascial mechanisms are probably of importance in episodic TTH, while sensitization of pain pathways in the CNS—due to prolonged nociceptive stimuli from pericranial myofascial tissues and inadequate endogenous pain control may account for the conversion from ETTH to CTTH.
Acute therapy with NSAIDs is generally effective for the treatment of ETTH
There is little scientific evidence to guide the selection of treatment modalities in CTTH but best evidence is for tricyclics.

47. Thank you for your kind attention
Please feel free to contact me at any time with qustions or comments