Central modulation in cluster headache patients treated with occipital nerve stimulation: an FDG-PET study

Peer reviewe

Neuroimaging in cluster headache and other trigeminal autonomic cephalalgias

The central nervous system mechanisms involved in trigeminal autonomic cephalalgias, a group of primary headaches characterized by strictly unilateral head pain that occurs in association with ipsilateral craniofacial autonomic features, are still not comprehensively understood. However, functional imaging methods have revolutionized our understanding of mechanisms involved in these primary headache syndromes. The present review provides a brief overview of the major modern functional neuroimaging techniques used to examine brain structure, biochemistry, metabolic state, and functional capacity. The available functional neuroimaging data in cluster headache and other TACs will thus be summarized. Although the precise brain structures responsible for these primary headache syndromes still remain to be determined, neuroimaging data suggest a major role for posterior hypothalamus activation in initiating and maintaining attacks. Furthermore, pathophysiological involvement of the pain neuromatrix and of the central descending opiatergic pain control system was observed. Given the rapid advances in functional and structural neuroimaging methodologies, it can be expected that these non-invasive techniques will continue to improve our understanding into the nature of the brain dysfunction in cluster headache and other trigeminal autonomic cephalalgias

Abnormal cortical responses to somatosensory stimulation in medication-overuse headache

BACKGROUND: Medication-overuse headache (MOH) is a frequent, disabling disorder. Despite a controversial pathophysiology convincing evidence attributes a pivotal role to central sensitization. Most patients with MOH initially have episodic migraine without aura (MOA) characterized interictally by an absent amplitude decrease in cortical evoked potentials to repetitive stimuli (habituation deficit), despite a normal initial amplitude (lack of sensitization). Whether central sensitization alters this electrophysiological profile is unknown. We therefore sought differences in somatosensory evoked potential (SEP) sensitization and habituation in patients with MOH and episodic MOA. METHODS: We recorded median-nerve SEPs (3 blocks of 100 sweeps) in 29 patients with MOH, 64 with MOA and 42 controls. Episodic migraineurs were studied during and between attacks. We measured N20-P25 amplitudes from 3 blocks of 100 sweeps, and assessed sensitization from block 1 amplitude, and habituation from amplitude changes between the 3 sequential blocks. RESULTS: In episodic migraineurs, interictal SEP amplitudes were normal in block 1, but thereafter failed to habituate. Ictal SEP amplitudes increased in block 1, then habituated normally. Patients with MOH had larger-amplitude block 1 SEPs than controls, and also lacked SEP habituation. SEP amplitudes were smaller in triptan overusers than in patients overusing nonsteroidal anti-inflammatory drugs (NSAIDs) or both medications combined, lowest in patients with the longest migraine history, and highest in those with the longest-lasting headache chronification. CONCLUSIONS: In patients with MOH, especially those overusing NSAIDs, the somatosensory cortex becomes increasingly sensitized. Sensory sensitization might add to the behavioral sensitization that favors compulsive drug intake, and may reflect drug-induced changes in central serotoninergic transmission

Altered processing of sensory stimuli in patients with migraine

Migraine is a cyclic disorder, in which functional and morphological brain changes fluctuate over time, culminating periodically in an attack. In the migrainous brain, temporal processing of external stimuli and sequential recruitment of neuronal networks are often dysfunctional. These changes reflect complex CNS dysfunction patterns. Assessment of multimodal evoked potentials and nociceptive reflex responses can reveal altered patterns of the brain's electrophysiological activity, thereby aiding our understanding of the pathophysiology of migraine. In this Review, we summarize the most important findings on temporal processing of evoked and reflex responses in migraine. Considering these data, we propose that thalamocortical dysrhythmia may be responsible for the altered synchronicity in migraine. To test this hypothesis in future research, electrophysiological recordings should be combined with neuroimaging studies so that the temporal patterns of sensory processing in patients with migraine can be correlated with the accompanying anatomical and functional changes

A review of diagnostic and functional imaging in headache

The neuroimaging of headache patients has revolutionised our understanding of the pathophysiology of primary headaches and provided unique insights into these syndromes. Modern imaging studies point, together with the clinical picture, towards a central triggering cause. The early functional imaging work using positron emission tomography shed light on the genesis of some syndromes, and has recently been refined, implying that the observed activation in migraine (brainstem) and in several trigeminal-autonomic headaches (hypothalamic grey) is involved in the pain process in either a permissive or triggering manner rather than simply as a response to first-division nociception per se. Using the advanced method of voxel-based morphometry, it has been suggested that there is a correlation between the brain area activated specifically in acute cluster headache — the posterior hypothalamic grey matter — and an increase in grey matter in the same region. No structural changes have been found for migraine and medication overuse headache, whereas patients with chronic tension-type headache demonstrated a significant grey matter decrease in regions known to be involved in pain processing. Modern neuroimaging thus clearly suggests that most primary headache syndromes are predominantly driven from the brain, activating the trigeminovascular reflex and needing therapeutics that act on both sides: centrally and peripherally

Placebo and other psychological interactions in headache treatment

We present a theory according which a headache treatment acts through a specific biological effect (when it exists), a placebo effect linked to both expectancy and repetition of its administration (conditioning), and a non-specific psychological effect. The respective part of these components varies with the treatments and the clinical situations. During antiquity, suggestions and beliefs were the mainstays of headache treatment. The word placebo appeared at the beginning of the eighteenth century. Controversies about its effect came from an excessive interpretation due to methodological bias, inadequate consideration of the variation of the measure (regression to the mean) and of the natural course of the disease. Several powerful studies on placebo effect showed that the nature of the treatment, the associated announce, the patients’ expectancy, and the repetition of the procedures are of paramount importance. The placebo expectancy is associated with an activation of pre-frontal, anterior cingular, accumbens, and periacqueducal grey opioidergic neurons possibly triggered by the dopaminergic meso-limbic system. In randomized control trials, several arms design could theoretically give information concerning the respective part of the different component of the outcome and control the natural course of the disease. However, for migraine and tension type headache attacks treatment, no three arm (verum, placebo, and natural course) trial is available in the literature. Indirect evidence of a placebo effect in migraine attack treatment, comes from the high amplitude of the improvement observed in the placebo arms (28% of the patients). This figure is lower (6%) when using the harder criterium of pain free at 2 h. But these data disregard the effect of the natural course. For prophylactic treatment with oral medication, the trials performed in the last decades report an improvement in 21% of the patients in the placebo arms. However, in these studies the duration of administration was limited, the control of attacks uncertain as well as the evolution of the co-morbid psycho-pathology. Considering the reviews and meta-analysis of complex prophylactic procedures, it must be concluded that their effect is mostly linked to a placebo and non-specific psychological effects. Acupuncture may have a slight specific effect on tension type headache, but not on migraine. Manual therapy studies do not exhibit difference between manipulation, mobilization, and controls; touch has no proven specific effect. A comprehensive efficacy review of biofeedback studies concludes to a small specific effect on tension type headache but not on migraine. A review of behavioral treatment conclude to an interesting mean improvement but did not demonstrated a specific effect with the exception of a four arm study including a pseudo meditation control group. Expectation-linked placebo, conditioning, and non-specific psychological effects vary according clinical situations and psychological context; likely low in RCT, high after anempathic medical contact, and at its maximum with a desired charismatic healer. The announcements of doctors strongly influence the beliefs of patients, and in consequence their pain and anxiety sensibilities; this modulates the amplitude of the placebo and the non-specific psychological effects and is therefore a major determinant of the therapeutic success. Furthermore, any repetitive contact, even through a placebo, may interfere positively with the psychopathological co-morbidity. One has to keep in mind that the non-specific psychological interactions play a major role in the improvement of the majority of the headache sufferers