Benign Headache and Diagnosis Pathophysiology. Dr Andrew J Dowson Director of the King s Headache Service King s College Hospital London

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1 Benign Headache and Diagnosis Pathophysiology Dr Andrew J Dowson Director of the King s Headache Service King s College Hospital London

2 Case histories

3 Case 1 Male, 46 y - Truck driver - Headaches since 26 y Trigger light - Oncoming traffic - Reflection off windscreen - Winter sun First symptoms - Black hole in vision gradually enlarging - At 25 min vision normal At 30 minutes - Right frontal pain - Throbs - Worse with activity - Moderate - Photophobia - No nausea / phonophobia

4 Case 1 Male, 46 y - Truck driver - Headaches since 26 y Trigger light - Oncoming traffic - Reflection off windscreen - Winter sun First symptoms - Black hole in vision gradually enlarging - At 25 min vision normal At 30 minutes - Right frontal pain - Throbs - Worse with activity - Moderate - Photophobia - No nausea / phonophobia Migraine with aura

5 Migraine phases Aura Prodrome Headache Resolution / recovery Impact Time

6 Migraine with aura: CBF Hypoperfusion Hyperperfusion Normal CBF Aura Headache Hours after angiography

7 Defective central antinociceptive system Areas of red indicate cerebral blood flow increases (P<0.001). Weiller C, et al. Nat Med

8 Patent foramen ovale (PFO) What is a PFO? Association between PFO and migraine The MIST trial

9 What is a PFO?

10 Syndromes associated with right to left shunts (PFO Arterial hypoxaemia Paradoxical thromboembolism and stroke Paradoxical gas embolism and decompression illness Migraine with aura Transient global amnesia

11 PFO identified using a TTE with contrast bubble study

12 Prevalence and size of shunts 27.3% of population have a PFO. (Mayo Clin Proc 1984;59:17-20) Using our criteria/technique 27.6% of controls have a shunt but only 7.3% are large - 4.9% at rest and 2.4% only with Valsalva. (Clinical Science 2000;99:65-75) Risk of DCI is related to shunt size.

13 Association between PFO and migraine Numerous studies have demonstrated an increased prevalence of PFO and other right to left shunts in migraine patients, particularly those with aura Inheritance of migraine is linked to inheritance of atrial shunts in some families 1 Prevalence of migraine is related to the size of the shunt 2 1 Heart 2004;90: ; 2 Clin Sci 2005;108:365-7.

14 Migraine with aura associated with shunt size (n = 400) % Migraine with aura None Small Medium Large Clin Sci 2005;108:365-7.

15 Effect of PFO closure on migraine Study Wilmshurst 2000 No. migraine/ no. closed (%) % migraine improved or cured Length of follow up (months) 21/37 (57%) 86% up to 30 Morandi /62 (27%) 88% all 6 Schwerzmann /215 (22%) 81% all 12 Post /66 (39%) 65% cured all 6 Reisman /120 (42%) 90% mean 4 Azarbal /89 (42%) 76% all 3 Reisman /162 (35%) 70% all 12

16 Effect of PFO closure on migraine Study Wilmshurst 2000 No. migraine/ no. closed (%) % migraine improved or cured Length of follow up (months) 21/37 (57%) 86% up to 30 Morandi /62 (27%) 88% all 6 Schwerzmann 2004 Migraine improved in 80% of people following PFO closure 48/215 (22%) 81% all 12 Post /66 (39%) 65% cured all 6 Reisman /120 (42%) 90% mean 4 Azarbal, /89 (42%) 76% all 3 Reisman /162 (35%) 70% all 12

17 The MIST (Migraine Intervention with STARFlex Technology) trial A prospective, randomised, multicentre, double-blind, placebocontrolled trial to evaluate the effectiveness of patent foramen ovale closure with the STARFlex septal repair implant to prevent migraine headache

18 MAA Clinic Files News Patient source Headache Clinic visit scheduled and patient receives PIS and video V1-24hr later C1+CRFs for Inclusion/Exclusion V2- C2/TTE/Implant Ed/Bloods V1-V10= visits C1-C3=consents signed Nrs. Coordinator TTE/ Brompton or Shrewsbury Nrs. Coordinator TOE/Implant Centre MIPCA V3- C3/ECG/TOE/IVRS call/then Sham or Implant and ECG/TTE. website V4-9 Surveys, etc. V10 TTE Implant pt only

19 Inclusion Criteria yrs Male and female One year or more documented history of migraine Onset of migraine at age 50 yrs or less Minimum of 5 migraine headache days per month Minimum of 7 headache free days per month Migraine with aura Failure of 2 classes of prophylactic migraine medication PFO demonstrates moderate to large shunt

20 Inclusion Criteria PFO demonstrated by TTE & bubble study Shunt capacity grade 2-3 (moderate to large)

21 Prevalence and size of shunts in population studies 27.3% of population have a PFO 1 Transthoracic contrast echocardiography shows that 27.6% of controls have a shunt but only 7.3% are large - 4.9% at rest and 2.4% only with Valsalva 2 1 Mayo Clin Proc 1984;59:17-20; 2 Clin Sci 2000;99:65-75.

22 MIST: Shunts found in migraine patients (Jan-May 2005) n = 370 Migraine with aura (%) None 16.5 Small shunts 4.9 Large pulmonary 0.5 ASD 37.6 Large PFOs Large shunts (all types) = 43.0% Total shunts = 59.5%

23

24 Starflex septal occluder

25 PFO anatomy & closure

26 PFO anatomy & closure

27 PFO closure

28 Case 2 Female, 42 y - Teacher - Headaches since 12 y: 2 per mo - Wakes with headache - First day in bed with severe pain - Second day at 50%, but no headache - Left temporal sharp - Constant - Unable to move - Severe photophobia/ phonophobia / nausea

29 Case 2 Female, 42 y - Teacher - Headaches since 12 y: 2 per mo - Wakes with headache - First day in bed with severe pain - Second day at 50%, but no headache - Left temporal sharp - Constant - Unable to move - Severe photophobia/ phonophobia / nausea Migraine without aura

30 Triptans: Anti-migraine action Relief from pain and associated symptoms Cortex Thalamus Trigeminal ganglia 1 5-HT 1B Vasoconstriction 3 5-HT 1D Decreased pain transmission 2 Trigeminal Inhibition

31 Ergots versus triptans Ergots Triptan 5-HT 1A B D A +++ 2C +++ Adrenergic α α Dopamine D2 +++ Nausea/Emesis/ Dysphoria Anti-migraine Unnecessary Vascular Effects Asthenia Dizziness G.I./Nausea/Emesis

32 Case 3 Girl, 14 y - Schoolgirl - Headaches for 6/12: 1 per mo Trigger - Periods First symptom - Headache before evening meal Symptoms - Occipital - Throbbing - Worse with activity has fainted - Severe - Nausea has vomited - Photophobia

33 Case 3 Girl, 14 y - Schoolgirl - Headaches for 6/12: 1 per mo Trigger - Periods First symptom - Headache before evening meal Symptoms - Occipital - Throbbing - Worse with activity has fainted - Severe - Nausea has vomited - Photophobia Migraine without aura

34 Case 4 Male, 42 y - Primary care physician - Headaches for 10 y, variable frequency Towards end of stressful day - Generalised - Constant pressure - No relationship to exertion - Mild - No nausea - Mild photophobia

35 Case 4 Male, 42 y - Primary care physician - Headaches for 10 y, variable frequency Towards end of stressful day - Generalised - Constant pressure - No relationship to exertion - Mild - No nausea - Mild photophobia Muscle contraction (tension) headache

36 Case 5 Female, 46 y - Mother - Headache since horse-riding accident 20 years ago - Intermittent until 6/12 ago, now constant exacerbations - Occipital - Constant - Worse with activity - Can be severe - Nausea - Photophobia Treatments - Compound analgesic up to 10/d - Ibuprofen up to 3/d - Migraine specific up to 2/d

37 Case 5 Female, 46 y - Mother - Headache since horse-riding accident 20 years ago - Intermittent until 6/12 ago, now constant exacerbations - Occipital - Constant - Worse with activity - Can be severe - Nausea - Photophobia Treatments - Compound analgesic up to 10/d - Ibuprofen up to 3/d - Migraine Specific up to 2/day Chronic daily headache

38 Chronic daily headache (CDH) 10 a. Chronic tension-type headache Headache severity Months

39 Chronic daily headache (CDH) 10 b. Migraine superimposed over CTTH Headache severity Months

40 Chronic daily headache (CDH) 10 c. Chronic migraine Headache severity Weeks

41 CDH presentations Headache severity 10 5 Chronic tension-type headache Headache severity 10 Chronic migraine Months 10 Migraine superimposed over CTTH Weeks Headache severity Months

42 Case 6 Boy, 12 y - Schoolboy - Monthly attacks abdominal pain - 2 days off school - Divorced parents - Both parents have migraine - No headache - Site varies during an attack and between attacks

43 Case 6 Boy, 12 y - Schoolboy - Monthly attacks abdominal pain - 2 days off school - Divorced parents - Both parents have migraine - No headache - Site varies during an attack and between attacks Abdominal pain syndrome Migraine equivalent

44 Other migraine equivalents Cyclical vomiting Paroxysmal vertigo Flitting limb pains

45 Case 7 Female, 54 y - Secretary - Intermittent headaches all life - For last 4 weeks different - Wakes in middle of night - Paces round bedroom - Red right eye - Blocked right nostril - Lasts for 90 min

46 Case 7 Female, 54 y - Secretary - Intermittent headaches all life - For last 4 weeks different - Wakes in middle of night - Paces round bedroom - Red right eye - Blocked right nostril - Lasts for 90 min Cluster headache

47 Case 8 Female, 64 y - Frontal headache for 2 d - Wants Rx for sinusitis Examination - No temperature - No nasal discharge

48 Case 8 Female, 64 y - Frontal headache for 2 d - Wants Rx for sinusitis Examination - No temperature - No nasal discharge - Often preceded by lethargy for 1 d - Has numb right hand for 30 min before attack - Headache clears after 2 days following antibiotics

49 Case 8 Female, 48 y - Frontal headache for 2 d - Wants Rx for sinusitis Examination - No temperature - No nasal discharge - Often preceded by lethargy for 1 d - Has numb right hand for 30 min before attack - Headache clears after 2 days following antibiotics Not sinusitis Migraine with aura

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