**5. Discussion**

92 Sleep Disorders

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

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

Headache subjects - satisfied by their sleep 11,4 94,6 5,4 Headache subjects - not satisfied by their sleep 15,1 94,2 6,8 Controls - satisfied by their sleep 23,3 93,1 12,8 Controls - not satisfied by their sleep 23,4 92,6 16,5

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

 **AHI SaO2 media T<90%**  Headache subjects with short sleep latency 15,6 94,3 6,8 Headache subjects with long sleep latency 9,6 94,5 4,2 Controls with short sleep latency 26,0 92,8 14,3 Controls with long sleep latency 14,8 93,7 17,7

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

**AHI SaO2 media T<90%** 

short vs long sleep latency and patients with frequent vs sporadic awakenings.

*Respiratory sleep parameters in different sleep behavior groups* 

quality.

parameters during sleep.

blood oxygenation.

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 condition during sleep, also in allodynic cases.

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 unbalance.

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 included.

**1. Introduction** 

(Mohsenin, 2003; Yaggi, 2003).

**8** 

Rafał Rola

*Poland* 

**Sleep-Disordered** 

*Institute of Psychiatry and Neurology* 

**Breathing in Neurological Diseases** 

Episodes of hypoxia and hypercapnia occurring during apneas significantly dilate blood vessels in the brain (both hypercapnia and hypoxia are potent stimuli of cerebral blood vessels dilation - Guyton, 2005). This results, together with a concomitant increase of mean arterial pressure, in average blood flow increase in the cerebral vessels. Studies in healthy volunteers (Przybylowski, 2003) have shown that episodes of breath apneas cause an increase of cerebral blood flow compared with resting conditions (43% on average). Following an episode of apnea, hyperventilation (with normoxia and hypocapnia) significantly decreases flow in the middle cerebral artery as compared to quiet breathing by 20% (Przybylowski, 2003). In normal subjects sleep reduces the vasodilatation response to a hypoxia (Meadows, 2004). A number of different mechanisms triggered during sleep apneas can influence the blood flow in the brain. The increase in intracranial pressure, together with a negative pressure in the chest, may reduce the perfusion of the brain (Jennum, 1989). More frequent significant carotid artery stenosis (Silvestrini et al, 2002; Nachtmann et al, 2003) and flow disturbances in the intracranial arteries (Behrens et al, 2002; Nachtmann et al, 2003) were found in patients with sleep-disordered breathing as compared with a population of healthy controls. There was also found that: cerebrovascular autoregulation reserve and hypercapnia triggering cerebral blood vessels dilatation are reduced in patients with obstructive sleep apneas as compared with the control group (Balfors, 1994). Similarly, studies of cerebral blood flow autoregulation in patients with sleep disordered breathing show impaired and delayed expansion of cerebral blood vessels in response to hypoxia (Urbano, 2008). Short-term mechanisms, associated with airway obstruction and hypoxia during sleep, are of paramount importance in the pathophysiology of cerebral circulation disorders and ischemic stroke. During obstructive apnea there is a temporary increase in blood flow through the brain vessels due to hypoxia and hypercapnia, but this increase is smaller than that of healthy people. Hyperventilation which follows the apnea causes hypocapnia and normoxia with significant reduction of blood flow through the brain vessels. Obstructive sleep apnea promotes a substantial fall in cerebral blood flow (Culebras et al, 2004; Netzer et al, 1998). It seems that short-term mechanisms, associated with apnea during sleep, underlie the observed periodicity of brain ischemic stroke occurrence during the day and more frequent prevalence of ischemic stroke in the early morning hours

To explore this unexpected hypothesis, we grouped both headache and non-headache subjects by sleep subjective satisfaction, sleep latency, and presence of awakenings. Comparing groups (headache subjects with short vs long sleep latency, with frequent vs sporadic awakenings and satisfied vs non-satisfied) no significant difference emerged, at least after Bonferroni correction. Probably the relatively small cohort dimension may have influenced the analysis.

The fact that patients with chronic headaches have a high prevalence of sleep complaints is well documented [09] and a high frequency of headache among patients with pathological breathing during sleep is well defined [02], but in the transitional phase toward sleep breathing disturbances, allodynia may be a useful para-physiological modification instead of a symptom of migraine transformation/chronification.
