M. Leone

Specific hypothalamic activation during a spontaneous cluster headache attack

Cluster headache, the most severe pain condition among the primary headache syndromes, is characterized by unilateral excruciating head pain and autonomic dysfunction.1 Functional neuroimaging has recently improved the pathophysiologic understanding of the different primary headache syndromes. Thereby, brainstem activation was found in migraine,2,3⇓ and hypothalamic overactivity was observed in nitrate-induced cluster headache4 and in short-lasting, unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT).5 Results of voxel-based morphometry support the role of the posterior hypothalamus in the pathogenesis of cluster headache because an increased gray matter density has been shown in this structure.6 However, the cluster headache attacks investigated so far were triggered with nitroglycerin (NTG). Although clinical and experimental data show NTG-provoked and spontaneous cluster attacks to be comparable and NTG does not alter regional cerebral blood flow (rCBF) significantly,4 the vasoactive properties of nitrates have to be considered, and data from spontaneous cluster attacks are desirable to confirm the mentioned results. We present a case of a spontaneous cluster attack during an ongoing H215O-PET study.nnA man (aged 30 years, right-handed, no medication) with a 2-year history of chronic cluster headache …

Lessons from 8 years' experience of hypothalamic stimulation in cluster headache

Neuroimaging studies in cluster headache (CH) patients have increased understanding of attack-associated events and provided clues to the pathophysiology of the condition. They have also suggested stimulation of the ipsilateral posterior inferior hypothalamus as a treatment for chronic intractable CH. After 8 years of experience, stimulation has proved successful in controlling the pain attacks in almost 60% of chronic CH patients implanted at various centres. Although hypothalamic implant is not without risks, it has generally been performed safely. Implantation affords an opportunity to perform microrecordings of individual posterior hypothalamic neurons. These studies are at an early stage, but suggest the possibility of identifying precisely the target site by its electrophysiological characteristics. Autonomic studies of patients undergoing posterior hypothalamic stimulation provide further evidence that long-term stimulation is safe, revealing that it can cause altered modulation of the mechanisms of orthostatic adaptation without affecting the baroreflex, cardiorespiratory interactions or efferent sympathetic and vagal functions. Chronically stimulated patients have an increased threshold for cold pain at the site of the first trigeminal branch ipsilateral to the stimulated side; when the stimulator is switched off, changes in sensory and pain thresholds do not occur immediately, suggesting that long-term stimulation is required to induce sensory and nociceptive changes. Posterior inferior hypothalamic stimulation is now established as a treatment for many chronic CH patients. The technique is shedding further light on the pathophysiology of the disease, and is also providing clues to functioning of the hypothalamus itself.

Increased familial risk of cluster headache

The authors studied the occurrence of cluster headache in the families of 220 Italian patients with cluster headache. A positive family history was found in 20% (44/220) of the families. Compared with the general population, first-degree relatives had a 39-fold significantly increased risk of cluster headache. Second-degree relatives had an eightfold significantly increased risk. The increased familial risk strongly supports the hypothesis that cluster headache has a genetic component in some families.

Sphenopalatine Endoscopic Ganglion Block: A Revision of a Traditional Technique for Cluster Headache

The diagnosis of chronic cluster headache (CH), the most painful form of headache, is based on typical clinical features characterized by strictly unilateral pain with no side shift and ipsilateral oculofacial autonomic phenomena. The attacks occur several times a day for periods of 1 to 2 months in the episodic form of the disease or less frequently on a daily basis in the chronic form. The pathogenesis of CH involves the activation of parasympathetic nerve structures located within the sphenopalatine ganglion (SPG), which explains many of the associated symptoms, whereas the activation of the ipsilateral hypothalamic gray matter may explain its typical circadian and circannual periodicity. A number of surgical approaches have been tried in cases of chronic CH resistant to pharmacologic therapy, of which SPG blockade has been shown to have certain efficacy. We have adopted a new technique based on endoscopic ganglion blockade that approaches the pterigo‐palatine fossa by way of the lateral nasal wall and consists of the injection of a mixture of local anesthetics and corticosteroids, which was performed in 20 selected patients with chronic CH, according to the International Headache Society criteria (18 male, 2 female; mean age 40 yr), who were selected for SPG blockade because they were totally drug resistant. The symptoms improved significantly, but always only temporarily, in 11 cases. These results should be considered rather good because, unlike other frequently used techniques, SPG blockade is not invasive and should therefore always be attempted before submitting patients to more invasive surgical approaches.

Acute hypothalamic stimulation and ongoing cluster headache attacks

Long-term hypothalamic stimulation is effective in improving drug-resistant chronic cluster headache (CH). We assessed acute hypothalamic stimulation to resolve ongoing CH attacks in 16 patients implanted to prevent chronic CH, investigating 136 attacks. A pain intensity reduction of ≥50% occurred in 25 of 108 evaluable attacks (23.1%). Acute hypothalamic stimulation is not effective in resolving ongoing CH attacks, suggesting that hypothalamic stimulation acts by complex mechanisms in CH prevention.

Health‐related quality of life in patients with cluster headache during active periods

Cluster headache is characterized by excruciatingly painful headaches which occur one or several times during the day. Little is known about the functional consequences of this severe headache form. We assessed health-related quality of life in 56 consecutive patients, 34 of whom were episodic cluster headache patients during an active period, and 22 had chronic cluster headache. All patients completed the Short Form-36 (SF-36). We found lower scores in the studied patients than in those reported in the general population for all SF-36 domains. For most scales the difference was significant (P < 0.0001, Students t-test, Bonferroni correction). Our findings suggest that cluster headache has marked functional consequences even when appropriate treatments are used.

Neuroimaging and pain: a window on the autonomic nervous system.

Pain is one of the most common experiences of humans. Neuroimaging techniques can visualize the main brain areas involved in pain modulation, the pain matrix. It is noteworthy that many of the brain areas forming the pain matrix are also involved in modulating autonomic nervous system (ANS) activity that in turn plays a major role in determining the best adaptive response to the pain experience. The tight connection between the pain system and ANS is also evident from neuroanatomical studies indicating that the lamina 1 neurons receive both painful and visceral stimuli from all visceral organs giving rise to the spinothalamocortical pathway concerned with conveying interoceptive information to central structures. The resulting interoceptive stream projects to the viscerosensory cortex in the mid-insula and onto the right anterior insula and orbitofrontal cortices. Right anterior insula activation is involved in the sympathetic arousal associated with mental tasks. This brain region receives numerous other inputs including pain and painful stimuli are conveyed somatotopically to both insulae. A similar somatotopic organization of painful stimuli has also been shown in the basal ganglia involved in cognitive, affective, motor and autonomic states. This highly specialized organization of nociceptive information in these brain areas may subserve a number of functions, particularly of coupling pain with the most appropriate autonomic states and affective/emotional states. The anterior cingulated cortex, another brain area playing a crucial role in nociception, is also directly involved in the control of autonomic functions such as arousal during volitional behaviour, including effortful cognitive processing. It is evident that the nociceptive system and ANS closely interact in many processes involved in maintaining internal homeostatis and in order to give the most appropriate biological substrate for cognitive, affective and emotional states.

Chronic high frequency stimulation of the posteromedial hypothalamus in facial pain syndromes and behaviour disorders

Chronic high frequency stimulation (HFS) of the posteromedial hypothalamus (PMH) has been the first direct therapeutic application of functional neuroimaging data in a restorative reversible procedure for the treatment of an otherwise refractory neurological condition; in fact, the target coordinates for the stereotactic implantation of the electrodes have been provided by positron emission tomography (PET) studies, which were performed during cluster headache attacks. HFS of PMH produced a significant and marked reduction of pain attacks in patients with chronic cluster headache (CCH) and in one patient with short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT). The episodes of violent behaviour and psychomotor agitation during the attacks of CCH supported the idea that the posteromedial hypothalamus could be also involved in the control of aggressiveness; this has been previously suggested, in the seventies, by the results obtained in Sanos hypothalamotomies for the treatment of abnormal aggression and disruptive behaviour. On the basis of these considerations, we have performed HFS of the PMH and controlled successfully violent and disruptive behaviour in patients refractory to the conventional sedative drugs. Finally, we also tested the same procedure in three patients with refractory atypical facial pain, but unfortunately, they did not respond to this treatment.

Clinical features and outcomes in spontaneous intracranial hypotension: a survey of 90 consecutive patients

Spontaneous intracranial hypotension (SIH) is a rare disabling condition whose main clinical manifestation is orthostatic headache. We analysed clinical characteristics in relation to time to resolution in 90 consecutive patients diagnosed with SIH at our centre between 1993 and 2006. After excluding 7 patients lost to follow-up, the remaining 83 cases were divided into four groups: Group A (53 cases) with progressively worsening orthostatic headache; Group B (3 cases) with severe acute-onset orthostatic headache; Group C (9 cases) with fluctuating non-continuous headache, of mild severity, that, in 33% of cases, did not worsen on standing; Group D (18 cases), 5 with a previous history of headache, 14 with orthostatic headache, and 10 with altered neurological examination. Complete symptoms and neuroradiological resolution occurred during follow-up in Groups A, B and D, but was longer in Group D probably in relation to more severe clinical picture with altered neurological examination. However, after a mean of 52xa0months (range 24–108), none of the nine Group C patients had MRI indicating complete resolution. The main characteristic of Group C related to incomplete resolution was delayed diagnosis. These preliminary findings suggest that early diagnosis of SIH correlates with better outcome, further suggesting that patients with a new headache that may worsen on standing or sitting should undergo MRI with contrast to expedite a possible SIH diagnosis, even if the pain is relatively mild.

The serotonergic agent m-chlorophenylpiperazine induces migraine attacks: A controlled study

Article abstract In a double-blind study versus placebo, the serotonergic agent m-chlorophenylpiperazine (mCPP) was administered to 20 healthy control subjects and 19 migraineurs to investigate the ability of mCPP (0.5 mg/kg) to induce typical migraine attacks. In the following 24 hours there were more migraines after mCPP than after placebo in both groups. These findings are consistent with involvement of 5HT2B,2C,1A receptor subtypes in the pathophysiology of migraine.