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Persistent idiopathic craniofacial pain (PIFP) is a heterogeneous group of pain syndromes whose main characteristic is the daily presence of persistent pain for at least 3 months. The pathophysiology of PIFP is still not entirely known and probably related to biological and psychological factors. Although PIFP has been attributed to the central neuron activity, the importance of masticatory muscles as a possible pathogenic mechanism was recently demonstrated. The main purpose of our paper was to identify the physiological rest position of the mandible with minimal tonus of both the elevator and depressor muscles and the neuromuscular trajectory of mouth closing obtained by transcutaneous electrical stimulation (TENS) and maintained with the use of an occlusal device, known as orthotic. The VAS scale for facial pain and the migraine disability assessment score (MIDAS) index for patient quality of life were evaluated at the beginning of the study for the 38 subjects that came to our attention. Our research included two phases. The first phase consisted of kinesiographic and electromyographic (EMG) examinations of the masticatory muscles and a 45-min application of TENS in order to deprogram the muscular activity. Kinesio-electromyographic examinations were repeated in the second phase. The main evaluated parameter was jaw deflection or deviation on the sagittal and frontal planes before and after TENS during patient tooth occlusion. Patients that showed a significant modification of this parameter were treated with orthotics for 12 months. The results of a 12-month follow-up show a sharp reduction of the VAS (pre-orthotic 9.05, range 8–10, SD 0.8; post-orthotic 5.87, range 1–5, SD 0.7) and an improvement in the quality of life (MIDAS). Our study demonstrated the usefulness of TENS as a screening method for the application of orthotics. This non-invasive and/or non-painful procedure could be a useful complementary treatment in this patient population. The results of the study also confirm the role of masticatory muscle dynamics as a possible pathogenic mechanism in patients with PIFP.

Persistent idiopathic craniofacial pain (PIFP) is a heterogeneous group of pain syndromes whose main characteristic is the daily presence of persistent pain for at least 3 months. The pathophysiology of PIFP is still not entirely known and probably related to biological and psychological factors. Although PIFP has been attributed to the central neuron activity, the importance of masticatory muscles as a possible pathogenic mechanism was recently demonstrated. The main purpose of our paper was to identify the physiological rest position of the mandible with minimal tonus of both the elevator and depressor muscles and the neuromuscular trajectory of mouth closing obtained by transcutaneous electrical stimulation (TENS) and maintained with the use of an occlusal device, known as orthotic.The VAS scale for facial pain and the migraine disability assessment score (MIDAS) index for patient quality of life were evaluated at the beginning of the study for the 38 subjects that came to our attention. Our research included two phases. The first phase consisted of kinesiographic and electromyographic (EMG) examinations of the masticatory muscles and a 45-min application of TENS in order to deprogram the muscular activity. Kinesio-electromyographic examinations were repeated in the second phase. The main evaluated parameter was jaw deflection or deviation on the sagittal and frontal planes before and after TENS during patient tooth occlusion. Patients that showed a significant modification of this parameter were treated with orthotics for 12 months.The results of a 12-month follow-up show a sharp reduction of the VAS (pre-orthotic 9.05, range 8-10, SD 0.8; post-orthotic 5.87, range 1-5, SD 0.7) and an improvement in the quality of life (MIDAS).Our study demonstrated the usefulness of TENS as a screening method for the application of orthotics. This non-invasive and/or non-painful procedure could be a useful complementary treatment in this patient population. The results of the study also confirm the role of masticatory muscle dynamics as a possible pathogenic mechanism in patients with PIFP.

The authors tried to establish whether there is any electrophysiological difference of masticatory muscle activity between patients with persistent idiopathic facial pain (PIFP) and healthy subjects. Twenty-eight PIFP patients (6 men and 22 women, mean age 40 years) and 28 normal subjects (12 men and 16 women, mean age 40 years) underwent EMG of temporal and masseter muscles before and after transcutaneous electric nerve stimulation (TENS). After TENS stimulation, the mean amplitude difference was found to be smaller than the baseline before TENS in the PIFP patients compared with healthy subjects. The peculiar behavior of masticatory muscles after TENS could be relevant in order to explain the well-known improvement of pain reported by some PIFP patients after orthosis positioning.

Background Medication reconciliation has been carried out since 2015 in the internal medicine ward. However, prescription errors at admission still occur, mainly linked to the transcription in the CPOE system by the physician of the medication history (MH) collected by the pharmacy. In order to improve the quality of prescription at admission, we studied the implementation of a pharmacist pre-prescription (PpP) process. Purpose To evaluate the impact of the PpP on the number of unintentional medication discrepancies (UMD) at admission. Material and methods Interventional prospective study before/after in a 24–bed internal medicine unit. Eligibility criteria: age >65 years and/or >three chronic treatments at admission. Pre–intervention phase (2 months): MH provided by the pharmacist and used by the physician to write the admission prescription. Intervention phase (2 months): MH entered by the pharmacist in the CPOE system as a PpP and then used by the physician to electronically generate an admission prescription without any transcription. Data collected: age, sex, number of UMD on the admission prescription, potential of harm for the patient (minor, moderate or severe) evaluated by the prescriber and the pharmacist, prescriber satisfaction (survey). Results Eighty patients (29 males, 51 females; age 68.4±18.6; medications at admission: 8.8±4.0) were included in the pre-intervention phase. 36.2% of patients had at least one UMD (0.53±0.80 UMD/patient). 40.4% of UMDs had a moderate or severe potential of harm for the patient. The main UMDs were dosage errors (38.0%) and omissions (33.3%). In the intervention phase, 47 patients (28 males, 19 females; age 66.3±18.7; medications at admission: 8.0±4.5) were included and PpP was used for 83% of them. Patients with at least one UMD decreased to 8.5% (p=4.2 × 10–5). Among the 39 patients for whom PpP was used, no UMDs were observed. The four physicians of the ward were satisfied with this new process as it allowed a reduction in medication errors and their time spent on admission prescription. Conclusion This study shows that pre-prescription by pharmacists decreases the number of UMD at admission. The main challenge for the future will consist in integrating PpP as part of the clinical pharmacist’s routine. References and/or acknowledgements No acknowledgements. No conflict of interest.

Background The hospital to community transition puts patients at an increased risk of having medication errors. In 2015, a discharge medication reconciliation (MR) process was implemented in the internal medicine ward. However, because discharge orders were being written at patients’ discharge, MR was completed once the patient had already left the hospital. This process made correction of discrepancies time-consuming (phone call to patient and patient’s GP). This is why in 2016, we decided, in collaboration with the internal medicine prescribers, to reorganise the discharge MR process. Purpose Implementation and assessment of a pre-discharge MR process in an internal medicine ward. Material and methods Discharge process from the internal medicine ward was reorganised and discharge orders were completed the day before patient’s discharge. Every morning, the pharmacist reviewed the discharge prescriptions of all the patients returning home and having received MR at admission (patients≥65 years old and/or having at least three chronic treatments). The discharge prescription was compared to the best possible medication history performed at admission and to the hospital prescription on the day of discharge in order to identify all the medication discrepancies. Discrepancies were then assessed with the prescriber to determine whether they were unintentional (UMD). UMD prevalence on discharge prescription and rate of UMD corrected were assessed and compared to the previous organisation (MR performed after patient’s discharge). Results During 3 months, 52 patients were included. Among the 436 medications prescribed at discharge, UMD prevalence was 6.4% (30) among which 93% (28) were corrected, leading to an uncorrected and maintained UMD prevalence of 0.5% (2/436) in discharge orders. This new MR discharge organisation led to a 79.6% decrease (2.3% to 0.5%) in UMD prevalence and a 2.3-fold increase (40% to 93%) in correction rate in comparison with the previous organisation model. Conclusion This study shows that anticipation of discharge prescriptions combined with MR is more effective in reducing UMD at discharge than a post-discharge MR. However, anticipation can sometimes be challenging in cases of numerous and/or unplanned discharge. In these cases, post-discharge MR could be performed to intercept and correct the main medication errors. No conflict of interest

BACKGROUND: The diagnostic accuracy of colonoscopy requires a perfect visualisation of the colonic mucosa, making bowel preparation a fundamental requisite of the procedure. Failure to adequately cleanse the bowel for colonoscopy results in an increase in costs and risks for patients, such as failed detection of neoplastic lesions, prolonged procedure duration and repetition of the examination. Due to recurrent failures observed in our hospital settings, a problem-solving approach was undertaken. PURPOSE: The aim of this study was to evaluate the quality of the pre-colonoscopy process of in- and outpatients (IOP) and identify potential dysfunctions. MATERIAL AND METHODS: In a 411-bed general hospital performing on average 90 colonoscopies per month, the colonoscopy reports of IOP from 1 January to 31 March 2017 were analysed. The rating of bowel preparation quality was determined according to the Boston Bowel Preparation Scale (BBPS). The laxative treatments used and the therapeutic indications were also recorded. A multidisciplinary team (MT) composed of a gastroenterologist, pharmacist, anaesthetist, nurse, senior nurse, endoscopist, dietetician and nurse-assistant met regularly for 6 months to assess the process, identify failure factors, create value-added flow and propose solutions to improve it. To compare the two groups, Student’s t or X (2) tests were used for continuous or dichotomous variables, respectively. RESULTS: Two hundred and ninety-seven colonoscopy reports corresponding to 284 patients were analysed (13 patients repeated the examination). Eighty patients (28%) experienced an inadequate bowel preparation (BBPS ≤6 or annotation on report). The most widely used laxative was polyethylene glycol. The number of failures was significantly higher among inpatients compared to outpatients (p

The aim of this study was to explore the possible role of tryptamine in the pathogenesis of chronic cluster headache along with that of adrenaline and noradrenaline (α-agonists) together with arginine metabolism in the origin of cluster bouts. Plasma levels of tyramine, tryptamine, serotonin, 5-hydroxyindolacetic acid, noradrenalin, adrenalin and the markers of arginine metabolism such as arginine, homoarginine, citrulline, ADMA and NMMA, were measured in 23 chronic cluster headache patients (10 chronic cluster ab initio and 13 transformed from episodic cluster) and 28 control subjects. The plasma levels of tyramine, tryptamine, noradrenalin and adrenalin were found several times higher in chronic cluster headache patients compared to controls, whereas the plasma levels of arginine, homoarginine and citrulline were significantly lower. No differences were found in the plasma levels of serotonin, 5-hydroxyindolacetic, ADMA and NMMA between chronic cluster headache patients and control subjects. These results provide support for a role of tryptamine in the pathogenesis of chronic cluster headache and, in particular, in the duration of the cluster bouts. In addition, the low levels of the nitric oxide substrates together with the high levels of noradrenalin and adrenalin suggest an activation of endothelial TAAR1 receptors followed by the release of nitric oxide in the circulation that may constitute the final step of the physiopathology of cluster crisis.

Chiari type 1 Malformation (CM 1) is a structural defect consisting of a displacement of the cerebellar tonsils through the foramen magnum causing obstruction of cerebrospinal fluid (CSF) outflow. CM 1 has a variety of presentation with headache being the most common symptom. The evaluation and treatment of headache related to CM 1 are often difficult, because the pain in the occipital-suboccipital region or headache that is of cough-type suggests symptomatic CM 1, but patients suffering from CM 1 can also report migraine or tension-type headache. In 2015 we started a collaborative project in which our group of neurologists, neurosurgeons and neuroradiologists contribute to create a Chiari Special Outpatient Service; this was set up to provide a multidisciplinary evaluation, treatment and follow-up of patient suffering from CM 1. 201 patients (58 males, 143 females) suffering from CM 1 were multidisciplinary evaluated. Headache characteristics, clinical features, and treatment of patients are discussed. Further progress in multidisciplinary care of headache and CM 1 should be performed to define guidelines.

The purpose of this paper is to present the results of a questionnaire investigating parafunctions (particularly clenching and grinding) in patients with chronic migraine presenting sign of temporomandibular disorder. The questionnaire was elaborated by the Dental Clinic of the University of Milano and completed by 125 patients experiencing chronic migraine and attending the Neurological Institute Carlo Besta for an inpatient withdrawal protocol to treat medication overuse. Our results showed high percentages of parafunctions, which were present in 80 % of patients. We note that patient information on possible behaviours and coexisting conditions which may be involved in the mechanisms of chronic headaches, as well as education about these factors, are crucial aspects in the management of chronic headache patients. We suggest that patients suffering from chronic migraine with medication overuse headache should be evaluated in relation to the possible presence of parafunctions, and as far as the need for interocclusal devices, in order to limit the role of temporomandibular dysfunctions as trigger factors or coexisting conditions favouring the development/maintaining of headache chronification.

Journal of applied physics 120(14), 145703 (2016). doi:10.1063/1.4964600, Unique electronic properties of semiconductor heterostructured nanowires make them useful for future nano-electronic devices. Here, we present a study of the band bending effect at the heterointerface of GaAs/InAs core/shell nanowires by means of synchrotron based X-ray photoelectron spectroscopy. Different Ga, In, and As core-levels of the nanowire constituents have been monitored prior to and after cleaning from native oxides. The cleaning process mainly affected the As-oxides and was accompanied by an energy shift of the core-level spectra towards lower binding energy, suggesting that the As-oxides turn the nanowire surfaces to n-type. After cleaning, both As and Ga core-levels revealed an energy shift of about −0.3 eV for core/shell compared to core reference nanowires. With respect to depth dependence and in agreement with calculated strain distribution and electron quantum confinement, the observed energy shift is interpreted by band bending of core-levels at the heterointerface between the GaAs nanowire core and the InAs shell., Published by American Inst. of Physics, Melville, NY

Following an allostatic perspective, episodic migraine (M) may be considered as an adaptive behavioural response to endogenous or exogenous stressors, while its progression to a daily or nearly daily form (chronic migraine) may represent the failure of adaptive strategies. Multiple factors may enhance the progression/chronification of M, and among these the presence of cutaneous allodynia (CA) as well as alterations in blood pressure and in sleep. The working hypothesis of the study was that subjects with M, and particularly those with CA, could show a tendency towards high blood pressure levels and/or to alterations in the circadian rhythm of blood pressure. We studied 235 subjects consecutively attending a centre for blood pressure control for a blood pressure 24 h monitoring. Headache diagnosis was made according to the ICHD-II criteria. The presence of CA was evaluated through a semi-structured ad hoc questionnaire. Blood pressure 24 h monitoring was performed by an ambulatory blood pressure monitor (Space Labs) with its ad hoc software. Seventy-eight subjects had a history of headache (mean age 54.0 ± 12.4 years, 18 men and 60 women); 56 of them had M, 22 had tension-type headache; among them, CA was found in 24/56 subjects with M, and in 6/22 with tension-type headache; 157 subjects did not suffer from headache (mean age 60.5 ± 11.5 years, 99 men and 58 women). No significant difference was observed between headache subjects and subjects without headache in terms of mean systolic and diastolic pressure, neither in the M nor in tension-type subgroups. With regard to the circadian rhythm of blood pressure, the physiological reduction during night (dipping) was more evident among headache subjects than in subjects without headache; this border-line difference was more strongly significant in subjects with CA than both non-headache (p = 0.003) and non-CA (p = 0.05) ones. The difference between allodynic and non-allodynic subjects was present also in the M sub-group (7 dippers out of 32 non-allodynic migraineurs vs. 12 dippers out of 24 allodynic migraineurs, p = 0.03) notwithstanding the reduction of the sample size. Despite the initial hypothesis, subjects with primary headaches did not show differences in terms of mean blood pressure values and they showed a more physiologic blood pressure daily rhythm than those without headaches. Also the presence of CA, a marker of progression to chronic headache forms, was associated neither with hypertension nor with increased frequency of loss of dipping. M, particularly when associated with allodynia, may improve breathing during nocturnal sleep and consequently counteract possible blood pressure alterations, suggesting an allostatic function of allodynic headache.

Objective. The primary aim was to investigate functional differences between medication overuse headache (MOH) patients and controls with the purpose of evaluating the presence of a global alteration in the processing of noxious stimuli throughout the pain matrix. The secondary aim was to investigate whether activations in MOH patients normalize after medication withdrawal, which would suggest a possible role of the pain matrix in headache chronification. Design. Functional magnetic resonance imaging was performed during painful mechanical stimulation in nine female patients with MOH immediately and at 6 months after beginning medication withdrawal, and in nine control participants. Results. Compared with controls, immediately after beginning withdrawal, the MOH patients showed reduced pain-related activity across the primary somatosensory cortex, inferior parietal lobule, and supramarginal gyrus, as well as in regions of the lateral pathway of the pain matrix. At 6 months, these differences were no longer detectable. Conclusion. Our findings suggest that significant functional changes occur in the lateral pain pathway in MOH patients. These could result from different processes: 1) cortical down-regulation aimed at reducing painful input to the cortex; 2) activity-dependent plasticity induced by excessive painful input during migraine attacks; and 3) direct effect of medication overuse. At 6 months after withdrawal, activity in these regions normalized, suggesting that no irreversible changes occur due to medication overuse.

Objective. We previously showed that DU significantly increased global and hand disability with a significant impact on activities of daily living (ADLs) and work disability. This study aims to evaluate the impact of digital ulcer (DU) healing on disability and daily activity limitations in SSc. Methods. From January 2008 and June 2009, we prospectively evaluated 189 SSc patients for DU history, disability, employment and occupational status during meetings of the French SSc Patient Association (n = 86, 45.5%) or during hospitalization (n = 103, 54.5%)1. Among the 60 patients with at least one active DU at baseline (M0), 40 patients were followed longitudinally over 6 (3) months. These patients were evaluated for DU history, global and hand disability, health-related quality of life (HRQoL), daily activity limitation and employment status. Results. The median (IQR) age was 57.5 (43.5-68) years and the median (IQR) disease duration was 8.3 (3-16.5) years. Twenty-two (55%) patients had diffuse SSc and 34 (85%) were females. At baseline, a mean of 2.9 (2.8) DU per patient was reported. Thirty-three (82.5%) patients had ischaemic DU, 7 (17.5%) patients had >1 DU associated with calcinosis and 13 (32.5%) patients had mechanical DU. Thirteen (32.5%) patients had >4 DU at baseline. Among the 40 patients, 16 (40%) patients showed complete ulcer healing. In these patients with DU, the presence of calcinosis was associated with a lower probability of healing (P = 0.03). Comparison between healed and no-healed DU patients showed an improvement of hand disability provided by an improvement of the Cochin Hand Function score (P = 0.05)) and a trend towards HAQ domain dressing and grooming (P = 0.06) between M0 and M6 (3) visit in healed patients but not in no-healed patients. Concerning HRQoL, there were no difference for Mental and Physical component Scores of SF-36 but significant improvement of Bodily Pain score (P = 0.04) and Physical Role score (P = 0.05) between M0 and M6 (3) visit in patients with healed DU. The absence of healing was associated with significantly decreased work productivity (P = 0.05), whereas the performance in ADL was not significantly decreased (P = 0.15). Patients who were on sick-leave and who received some help for household tasks at the time of active DU were more likely to heal. Conclusion. For the first time, we provide prospective data with evidence that DU healing is associated with an improvement in hand function. Sick leave was associated with better healing of DU

Spontaneous intracranial hypotension is an uncommon cause of sudden and persistent headache: associated symptoms are common, among which there are cranial nerve palsies, especially of the abducens nerve. We report a case of a 21-year-old man with a transient and isolated third nerve palsy due to spontaneous intracranial hypotension. To our knowledge, there are only few reports in the literature of such association.

Tweny patients (M: 4, F: 16, mean age 37 ± 11 years) with diagnosis of chronic daily headache (CDH), after drug withdrawal, were under electromyography, kinesiography and masticatory muscle deprogramming by TENS to identify the physiological rest position of the mandible. Our purpose was to clarify a possible role of the neuromuscular stomatognathic system. Examinations showed that 17 patients needed a neuromuscular orthosis, an occlusal device, to provisionally correct the detected discrepancies of jaw position. Of those, the 10 patients who showed an occlusal sagittal discrepancy higher than 2 mm and/or a lateral deviation higher than 0.4 mm, associated with more than three parafunctional activities, had a meaningful decrease on frequency/intensity of migraine crisis and/or of days of headache. VAS pain score during crisis decreased from 9.0 ± 0.9 to 4.9 ± 2.7; frequency of crisis were from 20.7 ± 5.2 to 9.5 ± 7.7. Baseline pain were from 5.3 ± 1.2 to 3.0 ± 1.3. Satisfying clinical results can be reached combining behavioural education and neuromuscular orthosis. This can be very helpful in patients who show significant discrepancy of jaw position that only TENS deprogramming can reveal and kinesiography can detect with such accuracy.

Chronic headaches have increasingly become a focus within the field of head pain. Most of the patients with frequent headache eventually overuse their medications, and if it happens [the percentage is approximately 4%], the diagnosis of chronic migraine with medication-overuse headache is clinically important, because patients rarely respond to preventive medications while overusing acute medications. This kind of headache is recognized as a biobehavioral disorder, a complex condition wherein emotion and pain are intermingled. Properly treating medication overuse with adequate strategies by different and specific steps are essential components for helping these patients to improve and for preventing relapses. The clinical experience performed at our Headache Unit, the necessity of withdrawal, different treatment schedules, and different treatment strategies of our center were discussed.

Migraine and depression are recognized as comorbid disorders on the basis of several epidemiological data and on the possibility of shared mechanisms. On the other hand, there is a lack of studies concerning therapeutic strategies in patients with this comorbidity. The aim of this paper is to briefly review the literature about the migraine and depression comorbidity and on the putative common neurobiological mechanisms, as well to discuss the possible therapeutic options in treating patients with both disorders.

Background: Menstrually related migraine (MRM) affects more than half of female migraineurs. Because such migraines are often predictable, they provide a suitable target for treatment in the mild pain phase. The present study was designed to provide prospective data on the efficacy of almotriptan for treatment of MRM. Methods: Premenopausal women with MRM were randomized to almotriptan ( N = 74) or placebo ( N = 73), taken at onset of the first perimenstrual migraine. Patients crossed over to the other treatment for the first perimenstrual migraine of their second cycle, followed by a two-month open-label almotriptan treatment period. Results: Significantly more patients were pain-free at two hours (risk ratio [RR] = 1.81; p = .0008), pain-free from 2–24 hours with no rescue medication (RR = 1.99; p = .0022), and pain-free from 2–24 hours with no rescue medication or adverse events (RR = 1.94; p = .0061) with almotriptan versus placebo. Nausea ( p = .0007) and photophobia ( p = .0083) at two hours were significantly less frequent with almotriptan. Almotriptan efficacy was consistent between three attacks, with 56.2% of patients pain-free at two hours at least twice. Adverse events were similar with almotriptan and placebo. Conclusion: Almotriptan was significantly more effective than placebo in women with MRM attacks, with consistent efficacy in longer-term follow-up.

Migraineurs brain is hyper-excitable and hypo-metabolic. Dreaming is a mental state characterized by hallucinatory features in which imagery, emotion, motor skills and memory are created de novo. To evaluate dreams in different kinds of headache. We included 219 controls; 148 migraineurs (66 with aura-MA, 82 without aura-MO); 45 tension type headache (TTH) patients. ICHD-II diagnostic criteria were used. Ad hoc questionnaire was used to evaluate oneiric activity. The Generalized Anxiety Disorder Questionnaire, and the Patient Health Questionnaire were administered to evaluate anxiety and mood. The prevalence of dreamers was similar in different groups. Frequency of visual and auditory dreams was not different between groups. Migraineurs, particularly MA, had an increased frequency of taste dreams (present in 19.6 % of controls, 40.9 % of MA, 23.2 % of MO, 11.1 % of TTH, p < 0.01), and of olfactory dreams (present in 20 % of controls, 36 % of MA, 35 % of MO and 20 % of TTH, p < 0.01). Anxiety and mood did not influence these results. The increased frequency of taste and olfactory dreams among migraineurs seems to be specific, possibly reflecting a particular sensitivity of gustative and olfactory brain structures, as suggested by osmofobia and nausea, typical of migraine. This may suggest the role of some cerebral structures, such as amygdala and hypothalamus, which are known to be involved in migraine mechanisms as well in the biology of sleep and dreaming.

In elderly patients, the differential diagnosis of primary headache complicated by clinical characteristics may suggest symptomatic headache. In addition, the frequent presence of chronic comorbidity illness and excessive analgesic use may aggravate a pre-existing headache or give rise to new headache to complicate headache management in elderly patients. This study reviews epidemiologic data, clinical characteristics and treatment options for primary headaches in elderly people.

Persistent idiopathic facial pain (PIFP) is a complex and uncertain nosographic entity, which has many aspects that need to be explored. The 21 patients selected (male 4 and female 17, mean age 40 years) were under electromyography (EMG) to determine the efficiency of the masseter muscles (MM) and the anterior temporalis muscles (TA), during activity and at rest, and under kinesiography (CMS) to identify the physiological rest position of the mandible after TENS stimulation. These patients were rehabilitated with a neuromuscular orthosis to provisionally correct the discrepancies identified. The EMG mean values of the muscles at rest were significantly above the normal (two-sample t test) for all four muscles and were normalized after the TENS session (Wilcoxon rank test). CMS showed that all 21 patients needed a mandibular advancement and 90.5% a correction in the frontal plane, obtained with orthosis. The comparison between the values of the maximal clench on natural dentition and on the orthosis showed a decrease in the asymmetry of muscular strength (-30.21% for TA and -55.81% for MM; Wilcoxon rank test) and a net increase of the strength expressed (LTA +25.37; LMM +59.40%, RMM +40.80%, RTA +30.27; Wilcoxon rank test; sign test). Preliminary results show a net decrease also in VAS pain score with a mean shift from 9.5 to 3.1. The results suggest a role for the neuromuscular component of the craniomandibular system in the pathogenesis of chronic idiopathic facial pain. All patients with PIFP should undergo the CMS-EMg examination.

Chronic migraine has been linked to the excessive use of acute headache medications. Medication overuse (MO) is commonly considered the most significant risk factor for the progression of migraine from an episodic to a chronic condition. Managing MO is a challenge. Discontinuation of the acute medication can result in withdrawal headache, nausea, vomiting and sleep disturbances. This review summarizes the results from two similarly designed, randomized, placebo- controlled, multicentre studies of chronic migraine conducted in the USA and European Union. Both studies demonstrate the efficacy and safety of the migraine preventive medication, topiramate, for the treatment of chronic migraine in patient populations both with and without MO. These studies may have important implications for the future of chronic migraine management, suggesting that detoxification prior to initiating prophylactic therapy may not be required in all patients if MO is present.

In a multicentric, open, preliminary trial, we evaluated the use of ginkgolide B, a herbal constituent extract from Ginkgo biloba tree leaves, in the prophylactic treatment of migraine with aura (MA). Fifty women suffering from migraine with typical aura, or migraine aura without headache, diagnosed according to International Headache Society criteria, entered a six-month study. They underwent a two month run-in period free of prophylactic drugs, followed by a four month treatment period (subdivided into two bimesters, TI and TII) with a combination of 60 mg ginkgo biloba terpenes phytosome, 11 mg coenzyme Q 10, and 8.7 mg vitamin B2 (Migrasoll), administered twice daily. A detailed diary reporting neurological symptoms, duration, and frequency of MA was compiled by patients throughout the trial. The number of MA significantly decreased during treatment (from 3.7 +/- 2.2 in the run-in period, to 2.0 +/- 1.9 during TI and to 1.2 +/- 1.6 during TII; Anova for repeated measures: P < 0.0001). There was also a statistically significant decrease in the average MA duration, which was 40.4 +/- 19.4 min during run-in, 28.2 +/- 19.9 during TI, and 17.6 +/- 20.6 during TII. Total disappearance of MA was observed in 11.1% patients during TI and in 42.2% of patients during T2. No serious adverse event was provoked by Migrasoll administration. Ginkgolide B is effective in reducing MA frequency and duration. The effect is clearly evident in the first bimester of treatment and is further enhanced during the second.

In about 20% of chronic cluster headache (CH) cases, drugs may become ineffective. Under these circumstances, steroids and triptans are frequently employed leading to fearful side effects in one and high costs in the other. The direct costs of drug-resistant chronic CH are mainly due to frequent medical consultations and frequent use of expensive drugs. In recent years, hypothalamic stimulation has been employed to treat drug-resistant chronic CH patients suffering multiple daily attacks and long-term results from different centres show a 60% overall benefit. Nine years since the introduction of this technique, we attempt a preliminary analysis of the direct costs of hypothalamic stimulation based on patients treated at our centre. We estimated the following direct costs as follows: cost of neurosurgery plus cost of equipment (electrode, connection and impulse generator = 25,000 euro), cost of hospital admissions in long-term follow-up (2,000 euro per admission), cost of single sumatriptan injection (25 euro). Number of daily sumatriptan injections in the year before and for each year after hypothalamic implantation was obtained from headache diaries. To estimate the saving due to the reduction in sumatriptan consumption following hypothalamic stimulation, we calculated the following for each year of follow-up after surgery: number of sumatriptan injections in the year before surgery minus number of sumatriptan injections in each year, updated to December 2008. In our 19 implanted patients, the costs of neurosurgery plus cost of equipment were 475,000 euro; the costs of hospital admissions during follow up were 250,000 euro. Reduction in sumatriptan consumption resulted in a total saving of 3,573,125 euro. Hence, in our 19 patients, the sumatriptan saving (3,573,125 euros) minus the direct costs due to operation and follow up hospitalisations (475,000 + 250,000) euro is equal to 2,848,125 euros. These preliminary results indicate that hypothalamic stimulation is associated with marked reduction of direct costs in the management of complete drug-resistant chronic CH.

A fixed location unilateral headache suggests involvement of a precise nervous structure, and neuroimaging investigations are essential to seek to identify it. Nevertheless, side-locked primary headaches also occur, although they are rare. Side-locked primary headaches are more frequently found in the group of the short-lasting (≤ 4 hours) headaches but long-lasting headache forms may also present with the pain always on the same side, including migraine, tension-type headache, new daily persistent headache and cervicogenic headache. Future studies should address the issue whether patients with side-locked headache form differ from those with non-side-locked form both in terms of natural history and biological markers. Among 63 consecutive chronic cluster headache patients seen by us from 1999 to 2007, 32 (51±) had side shift. We also found that the duration of the chronic condition was significantly longer in those with side shift than those without. The high frequency of side shift in chronic cluster headache should be considered when proposing surgical treatment for severe intractable forms of the disease.

The objective of this study was to determine the cardiovascular effects of chronic stimulation of the posterior hypothalamic area (PHA) in cluster headache (CH) patients. Systolic and diastolic blood pressure (SBP, DBP), cardiac output, total peripheral resistance (TPR), heart rate (HR) and breathing were monitored at supine rest and during head-up tilt test (HUTT), Valsalva manoeuvre, deep breathing, cold face test and isometric handgrip in eight drug-resistant chronic CH patients who underwent monolateral electrode implantation in the PHA for therapeutic purposes. Autoregressive power spectral analysis (PSA) of HR variability (HRV) was calculated at rest and during HUTT. Each subject was studied before surgery (condition A) and after chronic deep brain stimulation (DBS) of PHA (condition B). Baseline SBP, DBP, HR and cardiovascular reflexes were normal and similar in both conditions. With respect to condition A, DBP, TPR and the LF/HF obtained from the PSA of HRV were significantly (P < 0.05) increased during HUTT in condition B. In conclusion, chronic DBS of the PHA in chronic CH patients is associated with an enhanced sympathoexcitatory drive on the cardiovascular system during HUTT.

The aim of this study was to evaluate the efficacy and tolerability of topiramate for the prevention of chronic migraine in a randomized, double-blind, placebo-controlled trial. Chronic migraine is a common form of disabling headache presenting in headache subspecialty practice. Preventive treatments are essential for chronic migraine management, although there are few or no controlled empirical trial data on their use in this patient population. Topiramate is approved for the prophylaxis of migraine headache in adults. Patients (18-65 years) who experienced chronic migraine (defined as > or =15 monthly migraine days) for > or =3 months prior to trial entry and had > or =12 migraine days during the 4-week (28-day) baseline phase were randomized to topiramate or placebo for a 16-week, double-blind trial. Topiramate was titrated (25 mg weekly) to a target dose of 100 mg/day, allowing dosing flexibility from 50 to 200 mg/day, according to patient need. Existing migraine preventive treatments, except for antiepileptic drugs, were continued throughout the trial. The primary efficacy measure was the change in number of migraine days from the 28-day baseline phase to the last 28 days of the double-blind phase in the intent-to-treat population, which consisted of all patients who received at least one dose of study medication and had one outcome assessment during the double-blind phase. Health-related quality of life was evaluated with the Migraine Specific Quality of Life Questionnaire (MSQ, Version 2.1), the Headache Impact Test (HIT-6) and the Migraine Disability Assessment (MIDAS) questionnaires, and tolerability was assessed by adverse event (AE) reports and early trial discontinuations. Eighty-two patients were screened. Thirty-two patients in the intent-to-treat population (mean age 46 years; 75% female) received topiramate (mean modal dose +/- SD = 100 +/- 17 mg/day) and 27 patients received placebo. Mean (+/-SD) baseline number of migraine days per 4 weeks was 15.5 +/- 4.6 in the topiramate group and 16.4 +/- 4.4 in the placebo group. Most patients (78%) met the definition for acute medication overuse at baseline. The mean duration of treatment was 100 and 92 days for topiramate- and placebo-treated patients, respectively. Study completion rates for topiramate- and placebo-treated patients were 75% and 52%, respectively. Topiramate significantly reduced the mean number of monthly migraine days (+/-SD) by 3.5 +/- 6.3, compared with placebo (-0.2 +/- 4.7, P < 0.05). No significant intergroup differences were found for MSQ and HIT-6. MIDAS showed improvement with the topiramate treatment group (P = 0.042 vs. placebo). Treatment emergent adverse events were reported by 75% of topiramate-treated patients (37%, placebo). The most common AEs, paraesthesia, nausea, dizziness, dyspepsia, fatigue, anorexia and disturbance in attention, were reported by 53%, 9%, 6%, 6%, 6%, 6% and 6% of topiramate-treated patients, respectively, vs. 7%, 0%, 0%, 0%, 0%, 4% and 4% of placebo-treated patients. This randomized, double-blind, placebo-controlled trial demonstrates that topiramate is effective and reasonably well tolerated when used for the preventive treatment of chronic migraine, even in the presence of medication overuse.

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.

The objective of this study is to describe the therapeutic effect and the technical and surgical problems of deep brain stimulation (DBS) of the posterior hypothalamus over seven years, for treatment of chronic trigeminal autonomic cephalalgias and atypical facial pain. We report a surgical series of 20 patients that underwent DBS of the posterior hypothalamus. This series includes 16 patients with chronic cluster headache (CH), one patient with short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and three patients with atypical facial pain. All patients of this series were resistant to any pharmacological and conservative treatment. The stimulated target was the same in the whole series even though stereotactic coordinates of the target referred to the midcommissural point differ slight in the Y anteroposterior value due to individual anatomical variability. The commissures based reference system was adapted to individual anatomical landmarks of the brainstem adding to the registration a third reference point below the commissural plane. The stimulation parameters of unipolar stimulation were similar in the whole series: 180 Hz, 60 mus, 1-3 V. In the CH series, at five years follow-up the percentage of total number of days free from pain attacks improved from 1%-2% to 71%. Ten patients of this series had a complete and persistent pain-free state at 18 months follow-up and the patient with SUNCT has complete pain relief. In the three patients with atypical facial pain, the neurostimulation procedure was absolutely unsuccessful. DBS of the posterior hypothalamus produced a significant and marked reduction of pain bouts in CH patients and in the SUNCT patient. The attempts to treat atypical facial pain in three patients failed.

The association between headache and changes in intracranial pressure is strong in clinical practice. Syndromes associated with abnormalities of cerebrospinal fluid (CSF) pressure include spontaneous intracranial hypotension (SIH) and idiopathic intracranial hypertension (IIH). In 2013, the Headache Classification Committee of the International Headache Society (IHS) published the third International Classification of Headache Disorders (ICHD-3 beta version). The aim of this study was to investigate applicability of the new ICHD-3 versus ICHD-2 criteria in a clinical sample of patients with intracranial pressure (ICP) alterations. Patients admitted at our Headache Center for headache evaluation in whom a diagnosis of ICP alterations was performed were reviewed. 71 consecutive patients were studied. 40 patients (Group A) were diagnosed as IIH, 22 (Group B) as SIH, 7 (Group C) and 2 (Group D), respectively, as symptomatic intracranial hypertension and symptomatic intracranial hypotension. Main headache features were: in Group A, daily or nearly-daily headache (100 %) with diffuse/non-pulsating pain (73 %), aggravated by coughing/straining (54 %) and migrainous-associated symptoms (43 %). In Group B, an orthostatic headache (100 %) with nausea (29 %), vomiting (24 %), hearing disturbance (33 %), neck pain (48 %), hypacusia (24 %), photophobia (22 %) was reported. In Group C, a diffuse non-pulsating headache was present in 95 % with vomiting (25 %), sixth nerve palsy (14 %) and tinnitus (29 %). In Group D, an orthostatic headache with neck stiffness was reported by 100 %. Regarding applicability of ICHD-2 criteria in Group A, 73 % of the patients fitted criterion A; 100 %, criterion B; 100 %, criterion C; and 75 %, criterion D; while applying ICHD-3 beta version criteria, 100 % fitted criterion A; 97.5 %, criterion B; 100 %, criterion C; and 100 %, criterion D. In Group B, application of ICHD-2 showed 91 % patients fitting criterion A; 100 %, criterion B; 100 %, criterion C; and 68 %, criterion D; while applying ICHD-3 beta version all patients, 100 % fitted criterion A, B, C, D. 73 % patients of Group A fitted all ICHD-2 criteria and 97.5 % all ICHD-3 beta version criteria for headache attributed to IIH. 68 % patients of Group B fitted all ICHD-2 criteria and 100 % all ICHD-3 beta version criteria for headache attributed to SIH. In Group C and Group D, although patients fitted some clinical criteria, the underlying disorder caused exclusion of both ICHD-2 and ICHD-3 beta version applicability for headache attributed to IIH and SIH; they were coded in criteria for the secondary headaches. In summary, ICHD-3 beta version seems to have better applicability but worse reliability in defining headache features in CSF alterations.

Trace amines, including tyramine, octopamine and synephrine, are closely related to classic biogenic amines. In one study, where these substances were found elevated in plasma of migraineurs, it was hypothesized that trace amine metabolism is deranged in migraine. To confirm these findings, we studied, using a multichannel electrochemical high-performance liquid chromatography system, the concentrations of trace amines in platelets of migraine without aura (MoA) and migraine with aura (MA) patients in headache-free period, compared with controls. Platelet concentrations of trace amines, although elevated in both migraine types, showed a different profile in MoA and MA. Octopamine was significantly higher in MoA sufferers (0.69 ± 0.43 ng/108platelets) compared with both control subjects (0.22 ± 0.16 ng/108platelets) and MA patients (0.39 ± 0.37 ng/108platelets). Synephrine was significantly higher in MA patients (0.72 ± 0.44 ng/108platelets) with respect to both controls (0.33 ± 0.25 ng/108platelets) and MoA sufferers (0.37 ± 0.29 ng/108platelets). These results strengthen the hypothesis that tyrosine metabolism is deranged in migraine and may participate in its pathophysiology.

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.

Topiramate is approved for the preventive treatment of migraine in several countries based on the results of three large randomised, double-blind studies that showed that this compound was significantly more effective than placebo in migraine prophylaxis. We review the results of two studies: one which pooled data from the three controlled double-blind trials using 100 mg/day of topiramate, and an open-label extension of two of these trials in which patients received different topiramate doses for an eight-month maintenance period. The overall results confirm that topiramate is effective in reducing migraine frequency, and has a satisfactory tolerability profile.

Various treatment strategies have been proposed to help clinicians provide the most effective acute treatment for migraine patients. Stratified care is based on the concept that the most appropriate initial treatment can be prescribed after evaluation of each patient's headache characteristics. The results of a large multicentre trial showed that when patients were stratified according to disability grade, clinical outcomes were significantly better than with step-care approaches. Prospective studies have shown that treating migraines with triptans when pain is mild (early intervention) considerably increases success rates for endpoints (pain-free at 2 h, sustained pain-free state) for which triptans had relatively poor efficacy in pivotal trials, and which contribute most to patient satisfaction. Stratified care and early treatment are also cost-effective. However these strategies are not suitable for all patients. Stratified care may be rendered difficult by medication contraindications and changes in attack characteristics over time. Early triptan intervention carries a risk of medication overuse and might not be indicated in patients with lack of pain progression. Successful implementation of both strategies requires that physicians are well informed, and that they elicit an exhaustive headache history from each patient.

Topiramate has been shown to be effective as a preventive treatment for migraine in three large placebo-controlled, dose-ranging trials. Because the protocols were similar in design using the same primary and secondary endpoints, data from these studies were pooled to evaluate the consistency of efficacy, efficacy by gender and tolerability of topiramate 100 mg/day (n = 386) versus placebo (n = 372). Topiramate was superior to placebo as measured by the reduction in mean monthly migraine frequency, monthly migraine days and monthly migraine duration. The responder rates, defined as at least 50% reduction for the respective parameters, were significantly in favour of topiramate (p < 0.001), for example 46.3% of patients on topiramate achieved at least 50% reduction in monthly migraine period frequency compared with 22.8% on placebo (p < 0.001). Use of medication to treat the acute migraine attack was significantly reduced by topiramate compared with placebo (p < 0.001). The therapeutic effect was consistent throughout the different studies and independent of gender. The most common adverse effect was paraesthesia, mostly of mild-to-moderate severity. The findings confirm that, at a dose of 100 mg/day, topiramate is an effective and well-tolerated drug for migraine prevention.

Menstrual migraines are particularly difficult-totreat. Few studies on the use of triptans in short-term prophylaxis of menstrually related migraine have been recently conducted, but evidences of triptans' efficacy in the specific case of pure menstrual migraine (PMM) are lacking. The aim of this study is to explore the efficacy and tolerability of naratriptan as short-term prophylaxis of pure menstrual migraine (PMM) attacks. A multi-centre, open, non comparative, pilot six-month study was conducted in women, aged 18 years or older, with regular menstrual cycles and with a history of migraine without aura exclusively associated to the perimenstrual period. After an observation period of three months, patients took for three consecutive menstrual cycles oral naratriptan 1 mg twice daily, starting two days before the expected onset of menstruation and continuing for six days. Ninety-eight women with a history of PMM were screened for study participation, and 61 entered the study. Fifty-nine comprised the intent-to-treat population. The mean number of PMM attacks decreased from 3.5+/-1.4 in the 3-month observation period to 1.6+/-1.3 in the 3-month treatment with naratriptan. The pecentage of responders (subjects who recorded a decrease-equal or more than 50%-in the mean number of attacks) was 61.4%. A tendency towards a decrease in headache severity and in the presence of associated symptoms was observed during treatment. At least one adverse event during the treatment period was reported by 19 patients (31.1%). No serious adverse events occurred. Naratriptan may be an effective and safe treatment option in the short-prophylaxis of PMM.

This paper reviews results of placebo-controlled trials on topiramate (TPM) prophylaxis in migraine patients, and discusses issues regarding the use of this medication in clinical practice. Data from well conducted double-blind controlled trials and from a comparative trial show that TPM is effective against migraine, confirming the experience of physicians in various countries. Lack of major contraindications, high responder rate, good tolerability at the target dose (100 mg/day) following slow titration, and lack of weight gain make TPM one of the most effective and well accepted drugs for migraine prophylaxis.

Orofacial pain syndromes have traditionally been divided into two groups: the typical neuralgias and atypical facial pain. While typical neuralgias are well characterised, the term atypical facial pain (now persistent idiopathic facial pain) covers a variety of poorly defined head and face pains whose aetiological mechanisms are poorly understood. This paper examines the characteristics and nosography of these conditions, and suggests they should not be considered as neuralgias (section 13 of the 2004 IHS classification) but as other primary headaches (section 4).

Headache may occur in neurosarcoidosis and diagnostic criteria are given in the International Classification of Headache Disorders (ICHD-II). We present a case series of patients suffering from neurosarcoidosis in whom headache was the presenting symptom. The aim of the present study was to analyze the possible clinical presentations and the corresponding cerebral lesions in a retrospective chart review of patients suffering from neurosarcoidosis in whom headache was the presenting symptom. Medical records and data of six patients were analyzed. The possible diagnoses of headache forms included in ICDH-II, and in particular the correspondence with the criteria for "headache attributed to neurosarcoidosis", as well as neuroimaging findings were evaluated in each patient. The ICHD-II criteria were fulfilled in all the six patients. As for as clinical presentation, in three patients (50 %), headache had the clinical characteristics of Tolosa-Hunt syndrome, with evidence of a lesion into the cavernous sinus. In the remaining three cases headache was the only neurological symptom found in association with systemic features of sarcoidosis, and had the clinical features of tension-type headache. Our findings confirm that the clinical features of headache in patients with this disorder may have different presentations, which depend on neuropathologic involvement. Thus, a detailed neuroimaging study and CSF evaluation are needed to confirm diagnosis, particularly in patients with no sign of systemic sarcoidosis or in those in whom head pain may mimic a primary headache syndrome.

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.

Patients with chronic headache and medication overuse are particularly difficult to treat, with no one approach being universally accepted. Some type of withdrawal program, however, is typically implemented before beginning a pharmacological prophylaxis treatment. Different withdrawal modalities have been performed for managing these patients: at first step, in-patient withdrawal has been confirmed effective in preceding clinical experiences. In recent years, new modalities for withdrawal have been developed as day-hospital setting. Purpose of this study was to determine the clinical course of a sample of chronic migraine patients with medication overuse 3 years after day-hospital withdrawal. A group of 202 patients were treated. Patients were suffering from chronic migraine with medication overuse according with IHS criteria. All patients were submitted to a day-hospital withdrawal and then they were followed with meetings every 3 months until the first year and then every 6 months until the last follow-up 3 years after withdrawal. Eighty patients achieved the last follow-up meeting 3 years after withdrawal. Patients clinically improved, significantly, both for days of headache per month and consumption of medications per month. From these results, the day-hospital setting for withdrawal, followed by periodic clinical meetings, seems to be effective for this category of patients to improve significantly at long-term headache frequency and analgesics intake.

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.

Acetylsalicylic acid (ASA) in combination with metoclopramide has been frequently used in clinical trials in the acute treatment of migraine attacks. Recently the efficacy of a new high buffered formulation of 1000 mg effervescent ASA without metoclopramide compared to placebo has been shown. To further confirm the efficacy of this new formulation in comparison with a triptan and a nonsteroidal anti-inflammatory drug (ibuprofen) a three-fold crossover, double-blind, randomized trial with 312 patients was conducted in Germany, Italy and Spain. Effervescent ASA (1000 mg) was compared to encapsulated sumatriptan (50 mg), ibuprofen (400 mg) and placebo. The percentage of patients with reduction in headache severity from moderate or severe to mild or no pain (primary endpoint) was 52.5% for ASA, 60.2% for ibuprofen, 55.8% for sumatriptan and 30.6% for placebo. All active treatments were superior to placebo ( P < 0.0001), whereas active treatments were not statistically different. The number of patients who were pain-free at 2 h was 27.1%, 33.2%, 37.1% and 12.6% for those treated with ASA, ibuprofen, sumatriptan or placebo, respectively. The difference between ASA and sumatriptan was statistically significant ( P = 0.025). With respect to other secondary efficacy criteria and accompanying symptoms no statistically significant differences between ASA and ibuprofen or sumatriptan were found. Drug-related adverse events were reported in 4.1%, 5.7%, 6.6% and 4.5% of patients treated with ASA, ibuprofen sumatriptan or placebo. This study showed that 1000 mg effervescent ASA is as effective as 50 mg sumatriptan and 400 mg ibuprofen in the treatment of migraine attacks regarding headache relief from moderate/severe to mild/no pain at 2 h. Regarding pain-free at 2 h sumatriptan was most effective.

Clinicians working in the field of headache face great difficulty in managing patients with daily headache. Many of these patients have a history of episodic migraine that over several years has transformed into a chronic headache. Others have a history of episodic tension-type headache that also has chronicized. Still others present clinical characteristics that resemble both headache forms. In this article, we review the clinical and pathophysiological aspects of chronic daily headache and discuss the problems associated with its diagnosis.

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.

Patients with chronic migraine (CM) and medication overuse (MO) have a high frequency of psychiatric comorbidity or psychopathological traits, the presence of which may have important implications for the course of the CM and the MO, both for response to treatment and possible relapses. Overuse of symptomatic drugs is regarded as one of the most important risk factor for the transformation of episodic migraine into CM and drug-seeking tendency due to fear of headache in chronic migraine patients shares with obsessive-compulsive disorder (OCD) the compulsive quality of the behavior. Aim of this study was to review the clinical history of a sample of CM patients with MO in which an obsessive-compulsive trait was identified, performing a comparison with a sample of patients without obsessive-compulsive trait. We selected 14 patients with positivity to Spectrum Project OBS (obsessive-compulsive disorder) questionnaire and other 14 patients with negativity to the same tool from among a sample of patients who were enrolled in a previous study on the psychopathological profile of patients suffering from CM with MO. According to data obtained from the clinical records referring to the previous 5 years, patients with OBS questionnaire positivity showed a worse clinical course and a tendency to early relapse in MO after symptomatic medication withdrawal. Our results show that the comorbidity of OCD should be always evaluated in patients with CM and MO as it may play a relevant role--particularly if not treated--among the risk factors favoring the progression of episodic migraine to the chronic form, and/or the tendency to a pathological behavior that prompts the overuse of symptomatic medications.

Headache is a common symptom in children and adolescence. In this retrospective analysis, we interviewed a population of young patients who were arrived to our observation 10 years before, in order to: (1) determine if the first diagnosis was still adequate and (2) which percentage of these young patients developed chronic forms (more than 15 days/month) from episodic forms. One hundred and seventy-seven patients suffering from different forms of headache were contacted and interviewed. The original diagnosis was confirmed in all the population of patients and the percentage of chronic forms developed from episodic forms was not significant. From this retrospective study, it does not seem the evolution of episodic forms in young age is necessarily a chronic form in adult as this depends from other behavioural or biological or environmental factors.

Standard guidelines for ongoing management, as well as definitive data about the long-term course of idiopathic intracranial hypertension (IIH) are not available. The aim of this study was to compare several clinical and instrumental variables as assessed at the time of diagnosis and then after 1 year in a sample of IIH patients. A total of 21 patients were studied. Our results confirmed that headache and TVO are the most frequent symptoms in IIH patients, and that overweight is a very common feature. A trend towards a favorable outcome in patients followed for 1 year and treated by usual medical therapy was found: intracranial pressure was lower at follow-up; improvement of headache and transient visual obscurations, as well as of papilledema, was reported in most patients. On the other hand, neuroradiological findings (such as empty sella, perioptic subarachnoid space distension, narrowing of the transverse sinuses) were substantially stable at follow. These findings may be relevant for future research as far as understanding the role of different clinical and instrumental findings as diagnostic items as well as predictors of outcome in IIH.