**4. Results**

Among the enrolled subjects, 198 did not suffer from headache (mean age 60.3 ± 12.7 years, 159 men and 39 women) and 104 had history of headache (mean age 51.4 ± 12.3 years, 66 men and 38 women) of which 67 migraineurs (Mig - mean age 50.8 ± 14.9 years, 37 men and 30 women) and 37 with tension type headache (TTH - mean age 51.4 ± 13.3 years, 29 men and 8 women).

Out of 104 subjects with headache, 50 were allodynic. Allodynia was found in 41 out of 67 migraineurs and in 9 out of 37 patients with tension type headache.

*Headache and allodynia distribution in the sample* 

In our population, headache was present in 34.4% of the studied subjects (104 out of 302 individuals, of which 67 with migraine and 37 with tension type headache ) and allodynia during pain attacks was present in 48% of headache patients (50 out of 104 subjects). Allodynia was more frequent among migraineurs (41 out of 67) than in tension type patients (9 out of 37).

After grouping by gender, headache was present in 29,3% of men and in 49,3% of women. Migraine was found in 30 out of 39 female headache patients (30 out of 116 enrolled women, 25% of the female cohort) and in 37 out of 159 male patients with headache (37 out of 225 observed men, 16% of the male population studied). Headache distributions in the different groups are shown in Table 1.


Table 1. Presence of headache in subjects who underwent a full cardiopulmonary monitoring for presumed respiratory problems during sleep.

*Respiratory sleep parameters in different diagnostic groups* 

As summarized in Table 2, respiratory parameters among subjects with headache were always better than in subjects without headache.

Breathing Sleep Disturbances and Migraine: A Dangerous Synergy or a Favorable Antagonism? 91

As previously observed, allodynic subjects with headache, especially if migraineurs, complain of difficulties in falling asleep and of frequent awakenings that disrupt their nocturnal sleep. Tabs 3a, 3b and 3c summarize sleep characteristics in different groups of

> allodynic subjects n° (%)

Satisfied 111 (56) 37 (36) 17 (25) 20 (54) 11 (22) 26 (48) 6 (15) 11 (42) 5 (56) 15 (54) not satisfied 87 (44) 67 (64) 50 (75) 17 (46) 39 (78) 28 (52) 35 (85) 15 (58) 4 (44) 13 (46) tot. 198 104 67 37 50 54 41 26 9 28

Table 3a. Sleep behavior: subjective perception of sleep quality (satisfied/not-satisfied). Migraineurs – particularly allodynic ones – have a worse perception of their sleep quality

> allodynic subjects n° (%)

<30 minutes 159 (80) 72 (69) 42 (63) 30 (81) 30 (60) 42 (78) 22 (54) 20 (77) 8 (89) 22 (79) >30 minutes 39 (20) 32 (31) 25 (37) 7 (19) 20 (40) 12 (22) 19 (46) 6 (23) 1 (11) 6 (21) tot. 198 104 67 37 50 54 41 26 9 28

Table 3b. Sleep behavior: sleep onset latency. Migraineurs – particularly allodynic ones – take more time to fall asleep with respect to subjects without headache (chi2 test - p< 0.01 in

not allodynic subjects n° (%)

not allodynic subjects n° (%)

mig with allodynia n° (%)

mig with allodynia n° (%)

mig without allodynia n° (%)

mig without allodynia n° (%)

TTH with allodynia n° (%)

TTH with allodynia n° (%)

TTH without allodynia n° (%)

TTH without allodynia n° (%)

TTH without allodynia n° (%)

*Sleep behavior in different forms of headache* 

headache n° (%)

> Headache n° (%)

no headache n° (%)

<2 nights/month 70 (39) 26 (25) <sup>16</sup>

>3 nights/month 120 (61) 78 (75) <sup>51</sup>

headache n° (%)

mig n° (%)

(24)

(76)

TTH n° (%)

10

27

allodynic patients n° (%)

tot. 198 104 67 37 50 54 41 26 9 28

Table 3c. Sleep behavior: nocturnal awakenings. Migraineurs – particularly allodynic ones – wake more frequently during night with respect to subjects without headache (chi2 test - p<

not allodynic patients n° (%)

mig with allodynia n° (%)

(27) 7 (14) 19 (35) 4 (10) 12 (46) 3 (33) 7 (25)

(73) 43 (86) 35 (65) 37 (90) 14 (54) 6 (67) 21 (75)

mig without allodynia n° (%)

TTH with allodynia n° (%)

mig n° (%)

TTH n° (%)

with respect to subjects without headache (chi2 test - p< 0.01 in both cases).

TTH n° (%)

mig n° (%)

patients.

subjective satisfaction

> Sleep latency

both cases).

Nocturnal awakenings

0.01 in both cases).

no headache n° (%)

no headache n° (%)

The Apnea Hypopnea Index, that expresses the number of episodes of apnoea per hour, was 23.3 among subjects without headache and 13.8 in the headache group (p<0.01), without significant differences between different kinds of headache (14.2 in migraineurs and 13.1 in the tension type group).

Blood oxygenation during sleep was significantly better among headache patients (mean SpO2 94.4% and T90 6.3%) with respect to controls (mean SpO2 92.9% and T90 14.7%).

No differences were found between allodynic and non allodynic headache patients also with regard to specific diagnostic groups.


Table 2. Distribution of respiratory parameters among the different groups

Fig. 1. Blood oxygenation was better among migraineurs. In this diagnostic group, the time period with SpO2 < 90% was globally significantly shorter than in the other groups.

### *Sleep behavior in different forms of headache*

90 Sleep Disorders

The Apnea Hypopnea Index, that expresses the number of episodes of apnoea per hour, was 23.3 among subjects without headache and 13.8 in the headache group (p<0.01), without significant differences between different kinds of headache (14.2 in migraineurs and 13.1 in

Blood oxygenation during sleep was significantly better among headache patients (mean SpO2 94.4% and T90 6.3%) with respect to controls (mean SpO2 92.9% and T90 14.7%). No differences were found between allodynic and non allodynic headache patients also with

> **AHI Apnea Hypopnea Index**  (events/hour)

**SpO2** (mean oxygen saturation) (%)

**T<90%**  % of time with SpO2 < 90% (%)

**n°** 

Table 2. Distribution of respiratory parameters among the different groups

Fig. 1. Blood oxygenation was better among migraineurs. In this diagnostic group, the time

period with SpO2 < 90% was globally significantly shorter than in the other groups.

Subjects without headache, 198 23.3 92.9 14.7 **Headache subjects (Mig+TTH)** 104 13.8 94.4 6.3 Allodynic headache subjects 50 15.6 94.5 6.2 Non-allodynic headache subjects 54 12.1 94.3 6.4 **Subjects with TTH** 37 13.1 93.9 8.9 Allodynic TTH subjects 9 15.9 93.5 10.5 Non-allodynic TTH subjects 28 12.1 94.0 8.5 **Subjects with Mig** 67 14.2 94.7 4.8 Allodynic migraineurs 41 15.6 94.7 5.3 Non-allodynic migraineurs 26 12.0 94.7 4.0

the tension type group).

regard to specific diagnostic groups.

As previously observed, allodynic subjects with headache, especially if migraineurs, complain of difficulties in falling asleep and of frequent awakenings that disrupt their nocturnal sleep. Tabs 3a, 3b and 3c summarize sleep characteristics in different groups of patients.


Table 3a. Sleep behavior: subjective perception of sleep quality (satisfied/not-satisfied). Migraineurs – particularly allodynic ones – have a worse perception of their sleep quality with respect to subjects without headache (chi2 test - p< 0.01 in both cases).


Table 3b. Sleep behavior: sleep onset latency. Migraineurs – particularly allodynic ones – take more time to fall asleep with respect to subjects without headache (chi2 test - p< 0.01 in both cases).


Table 3c. Sleep behavior: nocturnal awakenings. Migraineurs – particularly allodynic ones – wake more frequently during night with respect to subjects without headache (chi2 test - p< 0.01 in both cases).

Breathing Sleep Disturbances and Migraine: A Dangerous Synergy or a Favorable Antagonism? 93

**AHI SaO2 media T<90%** 

awakenings 10,6 94,8 5,1

awakenings 15,0 94,2 6,8 controls with sporadic nocturnal awakenings 20,6 93,0 13,2 controls with frequent nocturnal awakenings 25,3 92,8 15,1

The study gave to somewhat unexpected results. Namely, the evidence of the significant difference observed between headache and non headache subjects in terms of mean AHI (p< 0.01), SpO2 (p < 0.01) and T <90% (p < 0.01) with better respiratory parameters among headache sufferers, particularly amongst the migraineurs. In fact, when we had planned the study, we were looking for possible endogenous elements able to induce and/or transform headache and we hypothesized that a sleep breathing disturbance might be one of this factors. On the contrary, it emerged that headache patients have a better respiratory

The analysis of sleep behavior in different groups showed that migraineurs took more time to fall asleep and awake more frequently during night with a reduced global sleep satisfaction. In conclusion, if compared to controls, migraineurs seem to sleep worse but to breathe better. However, the hypothesis that there is an allostatic function of migraine and allodynia could also be made: the presence of these conditions might inhibit deep sleep, and thus avoid prolonged apneas. The observation that allodynic patients complain of a poor subjective satisfaction by sleep with frequent awakenings and difficulties in starting sleep may be the time when an allostatic load (episodic migraine) becomes an allostatic overload (allodynic migraine), or it may correspond to a further allostatic adjustment to maintain an equilibrium: migraine is "sufficient" until the metabolic unbalance is such, that allodynia is needed. Allodynia is more frequently observed among subjects with chronic/transformed migraine, but it is also present in a large portion of episodic migraineurs. Probably transformed migraine is the true manifestation of the overwhelmed allostatic capacity of migraine (allostatic

overload) while the presence of allodynia is still a marker of a functional modification.

Overall, using an allostatic perspective, migraine may be considered a functional strategy to maintain equilibrium and to reverse situations potentially dangerous for the hyperexcitable and hypoenergetic migraineurs brain [08]. Transformed migraine may than represent the failure of this strategy (allostatic over-load), without the capacity to counteract the energetic

Allodynia (the perception of pain by non-painful stimuli) is largely considered as a marker of migraine transformation, but the observation that it is frequently present also among episodic migraineurs, offers another possible way to interpret this symptom. Allodynia may be an additional manifestation of migraine in an extreme effort to correct a metabolic or energetic or homeostatic disequilibrium, nocturnal sleep related blood oxygenation

Table 4c. Sleep behavior: subjects grouped by presence of nocturnal awakenings.

Respiratory parameters do not significantly differ among groups.

headache subjects with sporadic nocturnal

headache subjects with frequent nocturnal

condition during sleep, also in allodynic cases.

**5. Discussion** 

unbalance.

included.

Fig. 2. Migraineurs, particularly if allodynic, are less satisfied about their subjective sleep quality.

#### *Respiratory sleep parameters in different sleep behavior groups*

As showed in tables 4a, 4b and 4c, both subjects with and without headache were grouped by sleep behaviour characteristics (satisfaction, sleep latency and presence of nocturnal awakenings). No differences in terms of respiratory parameters were found comparing, in both headache and headache-free groups, subjects satisfied vs not satisfied, subjects with short vs long sleep latency and patients with frequent vs sporadic awakenings.


Table 4a. Sleep behavior: subjects grouped by subjective perception of sleep quality. Respiratory parameters among different groups. No significant differences between satisfied and not-satisfied in both headache and non-headache group with regard to respiratory parameters during sleep.


Table 4b. Sleep behavior: subjects grouped by sleep onset latency. Apnea episodes (AHI) are meanly more frequent among subjects with rapid sleep onset in both headache and nonheadache subjects (no difference after Bonferroni correction). No differences in term of blood oxygenation.


Table 4c. Sleep behavior: subjects grouped by presence of nocturnal awakenings. Respiratory parameters do not significantly differ among groups.
