Difficulties in work activities and the pervasive effect over disability in patients with episodic and chronic migraine.

Migraine is associated with reduced productivity in work-related activities. The degree to which problems with work are, in turn, associated to the level of migraine-related disability as well as to headache frequency has been poorly explored. The aim of the study was to assess if migraine patients with different degrees of work difficulties showed a different level of migraine-related disability. A consecutive sample of patients with episodic migraine (EM) or with chronic migraine (CM) with medication overuse (MO) attending the Headache Centre of the Neurological Institute C. Besta of Milan was studied. All patients completed the MIDAS and the WHODAS 2.0 questionnaires. The total scores of both questionnaires, frequency of headaches, average pain intensity, and the scores of each subscale of the WHODAS 2.0 were calculated separately for EM and CM patients. The score of WHODAS 2.0 "Work difficulties" subscale was used to divide the studied patients into two groups, i.e. those above and those below the median "Work difficulties" subscale score. Independent sample t test was used to compare these two groups as far as all the other studied variables. A total of 296 patients (102 with EM and 194 with CM-MO) were enrolled. Patients with higher work difficulties score also displayed higher scores in the other WHODAS 2.0 subscales; for those with CM-MO, the differences were significant. The results of this study indicate that having more and more severe workplace problems is associated to a higher disability level in migraineurs. Further studies are needed to better understand workplace disability in different migraine forms, particularly in a qualitative way.

Prevalence and profile of obsessive-compulsive trait in patients with chronic migraine and medication overuse.

Patients with chronic migraine (CM) and medication overuse headache (MOH) have high frequency of psychiatric comorbidity or psychopathological traits, the presence of which can influence the clinical course. The presence of subclinical obsessive compulsive disorder (OCD) is underestimated in migraine patients. The aim of this study was to estimate the prevalence and profile of obsessive-compulsive (OBS) trait in a sample of CM patients with MOH using the OBS questionnaire of Spectrum Collaborative Project. According to the new international classification of headache disorders (ICHD-III beta) criteria, 106 patients (15 M, 91 F, mean age 47.3 years) were selected in a consecutive clinical series. Our results showed that 36 % of patients with CM and MOH were positive at OBS-questionnaire. As far as the profile of OBS trait, we performed an evaluation of prevalence of items separating the first part of the questionnaire (childhood/adolescence and doubts in lifetime) from the other five domains: 21 % of the patients showed prevalence of items in childhood/adolescence domain; 79 % in doubts in lifetime domain; as for other five domains, 10.5 % of patients had prevalence of pathological answers among hypercontrol, 5.2 % in spending time, 23.7 % in perfectionism, 29 % in repetition and automation, and 31.5 % in specific themes (obsessive thoughts). The presence of subclinical OCD in migraine patients, and the link between progression to CM, particularly through MO, and OBS trait is still not well defined. The use of specific tools to assess this possible comorbidity should be encouraged in clinical and research settings.

Occipital neurostimulation in primary headaches: update.

A subset of headache patients are chronic and results refractory to standard medical treatments, they are unsatisfied or unable to tolerate the side effects of medications. In the lack of more effective prophylactic treatment, there is need of alternative approach. Migraine is conceptualized as a chronic and potentially progressive disorder. It is conceivable that more aggressive therapeutic efforts could be warranted in drug-refractory chronic migraine. In this prospective, the new, device-based therapies that allow to affect brain function in less invasive ways may represent a therapeutic opportunity. Peripheral occipital neurostimulation resulted in several trials and case reports to be beneficial in a large variety of headache and craniofacial pain disorders, with chronic primary headache the most studied. We comment on our experience in the application of ONS in drug-refractory chronic cluster headache and chronic migraine patients.

Positive outcome of occlusal freeway space reestablishment in patients with medication overuse due to chronic migraine.

Considering the great chapter of migraines, it is important to note the signs and symptoms caused by an alteration of the relationship of the facial musculature and the occlusal freeway space (FWS) that is the distance from maximal intercuspation to the habitual rest position (measurable in 1.4-2.5 mm). To any mandible position changing (detected by periodontal, muscle and joint proprioceptors), there is an influence on the neuromuscular system and then an alteration of the FWS. A group of 60 patients with chronic migraine (CM) underwent a withdrawal of overused medication and were subjected to electromyographic and kinesiographic evaluation. All those who presented an alteration of the FWS at rest position have been subjected to treatment with orthosis device for about 12 months. The aim of our work is to obtain and define a correct mandibular position, physiological, in agreement with the neuromuscular structures of the patient. Clinical results obtained on this pool of patients, in terms of reduction of the VAS, let us understand the importance of the inviolability of the FWS and to eliminate any type of mandibular deviation with respect to the closure trajectory induced by TENS in patients suffering from CM.

Outcome of patients with chronic migraine with medication overuse and depression after duloxetine: influence of coexisting obsessive compulsive disorder.

Patients with chronic migraine (CM) and medication overuse (MO) have high frequency of psychiatric comorbidity. Aims of this open label, prospective, independent study were: to evaluate the efficacy of duloxetine in a sample of patients with MO due to CM and with concomitant depression; to investigate, if the presence of OCD influences the outcome in this subgroup of patients. A total of 50 consecutive patients (40 F,10 M, aged 20-65 years, mean 39.4 years) from those attending our Headache Center to undergo an inpatient withdrawal programme followed by anti-migraine prophylaxis was enrolled. After a 1-month baseline period, all patients were prescribed duloxetine 30 mg in the morning for the first week, and 60 mg for the following 12 weeks. They filled a daily headache diary during the whole study period. They also completed Hamilton depression rating scale (HDRS) and migraine disability assessment scale (MIDAS) at baseline and at the 12-week follow-up. The primary outcome measure was the percentage of responders, i.e. of patients with a reduction ≥50 % in headache frequency as well as in symptomatic drug consumption. Comparison between patients with and without OCD was performed. Our results showed a rather high responder rate in the total sample (64 %), while none of the patients with OCD fell among responders. MIDAS and HDRS scores had a more evident decrease in patients without OSD. These findings suggest that duloxetine may be effective in patients with MO due to CM and with comorbid depression. They also confirm the importance of a systematic assessment of the psychopathological profile in these patients, and indicate that clinicians should be aware of the relevant prognostic role of OCD in favoring a poor outcome and persistent disability in headache patients with MO.

Drug-resistant chronic migraine: the Italian GON project.

Chronic daily headache is a major problem due to severe disability and high socio-economic costs. In the last years, some trials have shown potential benefit from new therapeutic approach by occipital neurostimulation techniques, already applied with some success for the treatment of chronic cluster headache. Due to the extremely heterogeneous population suffering from refractory chronic daily headaches, we propose a national multicenter experimental study involving Italian ANIRCEF Headache Centres with the aim to evaluate the efficacy of occipital neurostimulation in a selected group representative for the drug-resistant chronic migraine. Patients with chronic migraine according to Manzoni's modified IHS criteria-2011, with or without medication overuse headache, will be selected. Duration of illness should be at least 2 years and pharmacological refractoriness defined strictly for experimental-surgical purposes as those patients who have properly tried without success almost all available classes of prophylactic medications. Those presenting with medication overuse should have tried at least two previous detoxification treatments. A full psychopathological assessment will be performed by a psychiatrist, to exclude mainly psychotic disorder, ongoing severe status of an affective disorder, severe post traumatic stress disorder. Headache characteristics and abortive treatments used will be reported daily on a predisposed diary during 3-month baseline and continuously through the post implant follow up, while disability and QoL scale (MIDAS, SF-12) will be completed baseline, 6 and 12 months after implant.

Psychopathological profile of patients with chronic migraine and medication overuse: study and findings in 50 cases.

Patients with chronic migraine (CM) have high frequence of psychiatric comorbidity or psychological distress. The presence of depression, anxiety, panic or obsessive disorders in these patients contributes to poor quality of life and can influence prognosis and treatment. A systematic investigation of psychiatric comorbidity is needed in patients with CM especially in those with medication overuse (MO), in order to reach a more comprehensive clinical management. We assessed the psychological profile of 50 patients, 40 women and 10 men suffering from CM with MO. The Spectrum Project, a complementary way of describing and assessing psychopathology with structured clinical interviews, was used for the psychological evaluation of the patients to explore personality traits. Spectrum instruments mood disorders (MOODS), panic agoraphobic disorders (PAS) and obsessive-compulsive disorder (OBS) were applied to study patients. OBS-questionnaire was positive in 28% of the patients, MOODS-questionnaire in 44%, PAS-questionnaire in 46%. 19 on 50 patients (38%) presented positivity to 2 or to all questionnaires in variable associations. None of the patients of the studied group had complete normal findings in the questionnaires. Clinical records of patients with OBS-questionnaire positivity showed a worse clinical course and tendency to relapse. These results suggest that psychological assessment is an essential step in the evaluation and treatment of patients with CM and MO. The remarkable percentage of OBS-questionnaire positivity in this group indicates that obsessive-compulsive trait represents besides depression and anxiety, a major risk of chronification and overusing.

Polytherapy for the prophylaxis of chronic migraine: an Italian survey.

Chronic migraine (CM) represents an important medical issue, due to morbidity, high disability, presence of comorbidities, and medication overuse (MO). The prophylaxis of CM has not been extensively explored so far. Patients with CM are often treated with two or more compounds, although there is no clear evidence that polytherapy may be superior to monotherapy. We evaluated the percentage of prescription of polytherapy for the prophylaxis of CM in a clinical sample. We examined the charts of 98 CM patients admitted to our Headache Center for inpatient withdrawal program to stop MO. Results showed that only one drug for prophylaxis was prescribed in 20.4% cases, two or more drugs in 79.6%, with 63.3% of the total sample falling in the group "true polytherapy", i.e. all the drugs prescribed on daily basis were given to treat CM, and not only to treat concomitant conditions. In more than 60% cases a combination of drugs indicated for migraine prophylaxis and drugs only indicated for other conditions (mainly for psychiatric disorders) was prescribed. Our survey indicates that polytherapy may be rather common in CM, and suggests that comorbidities may strongly influence treatment choices.

Painful ophthalmoplegia: a retrospective study of 23 cases.

Painful ophthalmoplegia is a rare pathologic condition caused by non-specific inflammation of the cavernous sinus, but other causes such as tumours, vasculitis, basal meningitis, neurosarcoidosis, diabetes can be responsible for the syndrome. Aim of this study is a review of the cases of painful ophthalmoplegia admitted to our Institute in the last 20 years in order to verify the incidence of symptomatic versus benign forms in a clinical case series, with particular focus on the cases in which a long term (at least 4 years) and detailed follow-up did not revealed spread of any systemic disease or other presumed causes for painful ophthalmoplegia. Twenty-three patients were retrospectively studied, 12 patients (52%) were classified as benign forms and their disease course was again evaluated and 11 cases (48%) were designated as symptomatic. The present study suggests that in the clinical practice the incidence of benign forms among the painful ophthalmoplegias is more elevate than the symptomatic ones and underlines the need of a specific nosography for benign forms.

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.

Functional neuroimaging and headache pathophysiology: new findings and new prospects.

In the last ten years pathophysiology of primary headaches has received new insights from neuroimaging studies. Positron emission tomography (PET) showed activation of specific brain structures, brainstem in migraine and hypothalamic grey in trigeminal autonomic cephalalgias. This brain activation suggests it may intervene both in a permissive or triggering manner and as a response to pain driven by the first division of the trigeminal nerve. Voxel-based morphometry has 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. New insights into mechanisms of head pain have emerged thanks to neuroimaging obtained in experimentally induced headaches, and during peripheral and central neurostimulation.

Deep brain stimulation in craniofacial pain: seven years' experience.

Cluster headache (CH) is a primary headache with excruciatingly painful attacks that are strictly unilateral. About 10% of cases experience no significant remission, and about 15% of these do not respond to medication, so surgery is considered. Neuroimaging studies show that the posterior inferior hypothalamus is activated during CH attacks and is plausibly the CH generator. We report on 16 chronic CH patients, with headaches refractory to all medication, who received long-term hypothalamic stimulation following electrode implant to the posterior inferior hypothalamus. After a mean follow-up of 23 months, a persistent pain-free to almost pain-free state was achieved in 13/16 patients (15/18 implants; 83.3%) a mean of 42 days (range 1-86 days) after monopolar stimulation initiation. Ten patients (11 implants) are completely pain-free. A common side effect was transient diplopia, which limited stimulation amplitude. In one patient, a small non-symptomatic haemorrhage into the 3rd ventricle occurred following implant, but regressed 24 h later. Persistent side effects are absent except in one patient with bilateral stimulation, in whom stimulation was stopped to resolve vertigo and worsened bradycardia, but was resumed later without further problems. Hypothalamic stimulation is an effective, safe and well tolerated treatment for chronic drug-refractory CH. It appears as a valid alternative to destructive surgical modalities, and has the additional advantage of being reversible.

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.

Trigeminofacial reflexes in primary headaches.

Nociceptive processing in trigeminal system is likely to undergo to significant changes in chronic pain disorders such as in primary headache. The electrophysiological testing of brainstem reflexes seems to offer a valuable adjunct to the clinical evaluation, providing direct evidence for central dysmodulation of sensory and pain neurotransmission, i.e. dishabituation pattern and reduced pain threshold. We review the contribution of trigeminofacial reflex studies in the light of those recent data supporting the view of a dysfunctional sensory processing in primary headache.

Comparison of visual and auditory evoked cortical potentials in migraine patients between attacks.

OBJECTIVE: As both habituation of pattern reversal visual evoked potentials (PR-VEP) (Schoenen J, Wang W, Albert A, Delwaide PJ. Potentiation instead of habituation characterizes visual evoked potentials in migraine patients between attacks. Eur J Neurol 1995;2:115-122) and intensity dependence of auditory evoked cortical potentials (IDAP) (Wang W, Timsit-Berthier M, Schoenen J. Intensity dependence of auditory evoked potentials in migraine: an indication of cortical potentiation and low serotonergic neurotransmission? Neurology 1996;46:1404-1409) were found abnormal in migraine between attacks, we have searched for intraindividual correlations between both tests in 59 migraine patients (22 with aura [MA], 37 without aura [MO]) and in 23 healthy volunteers (HV). METHODS: Amplitude change of the PR-VEP N1-P1 was measured between the 1st and 5th block of 50 sequential averagings during continuous stimulation at 3.1 Hz. IDAP was computed from N1-P2 amplitudes of 100 averagings during stimulations at 40, 50, 60 and 70 dB SL. Amplitude-stimulus intensity function (ASF) slopes and amplitude changes between 40 and 70 dB were calculated. MO and MA differed from HV in PR-VEP amplitude change (P=0.007) and IDAP slope (P = 0.0004). RESULTS: There was no significant correlation between VEP amplitude changes and IDAP slopes, nor between the latter two and attack frequency or disease duration. A negative correlation was found between the amplitude of the first block of averaged responses and potentiation of VEP in all subject groups (P = 0.03) as well as between the amplitude of the auditory evoked potential, at 40 dB, and the percentage of amplitude increase between 40 and 70 dB in MO (P = 0.004) and MA (P = 0.007). ASF slopes and 40 dB amplitudes were significantly correlated only in the MA group (P = 0.002). These results confirm the interictal deficit of habituation in cortical processing of repetitive visual and auditory information in migraine. Since there is no intraindividual correlation between the cortical responses to these sensory modalities they are complementary tools for the study of migraine and may help to identify subgroups of patients with distinct pathophysiological mechanisms. CONCLUSIONS: The strong negative correlation between the initial amplitude of evoked potentials and their amplitude increase during subsequent averaging confirms that the response potentiation in migraine is likely to be due to a reduced preactivation level of sensory cortices.

From neurophysiology to genetics: cortical information processing in migraine underlies familial influences--a novel approach.

Migraine patients show impaired cortical information processing between attacks with deficient habituation of pattern-reversal visual evoked potentials (VEP), and strong intensity dependence of auditory cortical evoked potentials (IDAP). This could be a genetic trait as certain genetic patterns are known for evoked potentials in healthy subjects. VEP-habituation and IDAP were studied in 40 migraine patients, i.e. pairs of 20 parents and their children. We developed a novel approach based on Monte Carlo statistics to selectively assess vertical familial influences. Both groups, parents and children, were characterized by abnormal VEP-habituation and IDAP. However, similarity between related pairs was far more pronounced than similarity between unrelated pairs. Assessed with a novel statistical approach, familial influences proved to be highly significant in determining cortical information processing in migraineurs, thus supporting the important role of genetic factors.

Familial influences on cortical evoked potentials in migraine.

Cortical information processing in migraine patients is impaired between attacks, showing deficient habituation of pattern-reversal visual evoked potentials (VEP), and strong intensity dependence of auditory cortical evoked potentials (IDAP). This could be a genetic trait as certain genetic patterns are known for evoked potentials in healthy subjects. We investigated VEP habituation and IDAP in 20 pairs of migraineurs made up of parents and their children. Using a Monte-Carlo statistical method, we selectively assessed vertical familial influences. VEP habituation and IDAP were abnormal in both parents and children. However, similarity was far more pronounced between related pairs than between unrelated pairs. Familial influences are highly significant in determinants of cortical information processing in migraineurs, hence supporting the important role of genetic factors.

Neurophysiological approach to primary headache pathophysiology.

Electroencephalography (EEG), evoked potentials (EP), and electromyography (EMG) techniques are useful tools in the clinical assessment of headache and in understanding the pathophysiological mechanisms of these pathologies. EEG and EP studies in migraine revealed functional abnormalities in cortical electrical activity and in sensory processing. EMG studies resulted in pain syndromes involving nerves or myofascial structures such as tension-type headache and cluster headache. Moreover, it was possible to test the effect of old and new drugs with the help of these neurophysiological techniques. An updated review is reported of the literature.

Psychiatric comorbidity in chronic daily headache.

Clinical evidence suggests that chronic daily headache (CDH) occurs in association with psychopathologies: previous studies have focused particularly on migraine. To evaluate this association, we studied, using the DSM-IIIR criteria, a population of 88 patients (18M, 70F) affected by CDH (mean duration 7.4 +/- 8.7 years). We documented the presence of a psychiatric disorder in 90% of this population. The most frequent diagnosis was a comorbidity of anxiety and mood disorders. The comorbidity of psychiatric disorders and headache has important implications as far as treatment is concerned.