Poor patient awareness and frequent misdiagnosis of migraine: findings from a large transcontinental cohort.

BACKGROUND AND PURPOSE: Although migraine is the second most disabling condition worldwide, there is poor awareness of it. The objective was to assess the awareness of migraine and previous diagnostic and therapeutic consultations and treatments in a large international population of migraineurs. METHODS: This was a multicentre study conducted in 12 headache centres in seven countries. Each centre recruited up to 100 patients referred for a first visit and diagnosed with migraine. Subjects were given a structured clinical questionnaire-based interview about the perceptions of the type of headache they suffered from, its cause, previous diagnoses, investigations and treatments. RESULTS: In all, 1161 patients completed the study. Twenty-eight per cent of participants were aware that they suffered from migraine. Sixty-four per cent called their migraine 'headache'; less commonly they used terms such as 'cervical pain' (4%), tension headache (3%) and sinusitis (1%). Eight per cent of general practitioners and 35% of specialists (of whom 51% were neurologists and/or headache specialists) consulted for migraine formulated the correct diagnosis. Before participating in the study, 50% of patients had undergone X-ray, computed tomography and/or magnetic resonance imaging of the cervical spine and 76% underwent brain and/or cervical spine imaging for migraine. Twenty-eight per cent of patients had received symptomatic migraine-specific medications and 29% at least one migraine preventive medication. CONCLUSIONS: Although migraine is a very common disease, poor awareness of it amongst patients and physicians is still an issue in several countries. This highlights the importance of the promotion of migraine awareness to reduce its burden and limit direct and indirect costs and the risk of exposure to useless investigations.

Post Soft Care: Italian implementation of a post-stroke checklist software for primary care and identification of unmet needs in community-dwelling patients.

The needs of community-dwelling stroke patients are often not fully addressed. The Global Stroke Community Advisory Panel had developed the Post Stroke Checklist (PSC) with the aim of standardizing long-term stroke assessment and consequently care of patients. PSC has been validated for UK and Singapore, and an Italian version has been proposed. The aim of this study is to assess the needs of community-dwelling Italian stroke patients using an online version of PSC. Secondary aim is to assess utility of PSC for patients and clinicians. The PSC was administered to a sample of 64 patients with stroke in Italy by general practioners. PSC is a questionnaire formed by 11 questions, each one covering a domain identified as important for patients' health. After administration of PSC, patient and clinician satisfaction with the PSC was assessed by a specific questionnaire. The PSC identified specific problems for patients related to a worsening from the last examination not evaluated by any specialist. The online PSC highlighted problems related to mood, (in 50% of sample), mobility (53.1%), spasticity (42.2%), and pain (37.5%). Both patients and clinicians provided good results about the utility of online PSC. The PSC was confirmed to be a useful tool for identifying the needs of community-dwelling patients with stroke. Particular attention should be deserved to problems related to mood, mobility, and hence participation to social life, pain, and spasticity. For taking into account these aspects, the online PSC can be a useful portable tool for clinicians.

Psychopathological comorbidities in medication-overuse headache: a multicentre clinical study.

BACKGROUND AND PURPOSE: In medication-overuse headache (MOH) patients, the presence of psychopathological disturbances may be a predictor of relapse and poor response to treatment. This multicentre study aimed to assess the occurrence of psychopathological disorders in MOH patients by comparing the incidence of psychopathological disturbances with episodic migraine (EM) patients and healthy controls (HC). METHODS: The psychopathological assessment of patients and HC involved the administrations of the Beck Depression Inventory, the Beck Anxiety Inventory, the Modified Mini International Neuropsychiatric Interview (M-MINI), the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Leeds Dependence Questionnaire. RESULTS: The MOH, EM and HC groups (88, 129 and 102 subjects, respectively) differed significantly from each other for the presence of moderate/severe anxiety, whereas mood disorder and depression were revealed in similar proportions for both MOH and EM patients. By stratifying the M-MINI questionnaire results according to the number of psychiatric disorders, it was found that MOH patients had a more complex profile of psychiatric comorbidity. Furthermore, clinically relevant obsessive-compulsive disturbances for abused drugs assessed by Y-BOCS appeared to be more represented in the MOH group, whilst the prevalence of this trait in the EM group was comparable to that of HC (12.5%, 0.8% and 0%, respectively). CONCLUSIONS: Our study indicates the multiple presence of psychopathological comorbidities in patients with MOH. In light of this, it is recommended that the assessment of the psychopathological profile be included in an evaluation of MOH patients, allowing the clinician to more rapidly start an appropriate behavioural treatment, which would greatly improve MOH management.

Effects of peripheral FAAH blockade on NTG-induced hyperalgesia--evaluation of URB937 in an animal model of migraine.

BACKGROUND: Systemic nitroglycerin (NTG) activates brain nuclei involved in nociceptive transmission as well as in neuroendocrine and autonomic functions in rats. These changes are considered relevant for migraine because NTG consistently provokes spontaneous-like migraine attacks in migraineurs. Several studies have suggested a relationship between the endocannabinoid levels and pain mediation in migraine. URB937, a peripheral inhibitor of fatty acid amide hydrolase (FAAH)-the enzyme that degrades anandamide, produces analgesia in animal models of pain, but there is no information on its effects in migraine. AIM: We evaluated whether URB937 alters nociceptive responses in the animal model of migraine based on NTG administration in male rats, using the tail flick test and the plantar and orofacial formalin tests, under baseline conditions and after NTG administration. Furthermore, we investigated whether URB937 affects NTG-induced c-Fos expression in the brain. RESULTS: During the tail flick test, URB937 showed an antinociceptive effect in baseline conditions and it blocked NTG-induced hyperalgesia. URB937 also proved effective in counteracting NTG-induced hyperalgesia during both the plantar and orofacial formalin tests. Mapping of brain nuclei activated by NTG indicates that URB937 significantly reduces c-Fos expression in the nucleus trigeminalis caudalis and the locus coeruleus. CONCLUSIONS: The data suggest that URB937 is capable of changing, probably via indirect mechanisms, the functional status of central structures that are important for pain transmission in an animal model of migraine.

How to diagnose neuropathic pain? The contribution from clinical examination, pain questionnaires and diagnostic tests.

Patients with peripheral and central nervous system diseases may suffer from different types of pain, namely nociceptive, neuropathic and mixed pain. Although in some cases, the distinction between these types of pain is clinically evident, yet in some patients an accurate differential diagnosis requires dedicated clinical examination, screening questionnaires and diagnostic techniques some of which are available only in specialized pain centres. This review briefly addresses the currently agreed definitions of the different types of pain and shows how clinical examination, pain questionnaires and diagnostic tests can help the clinicians in identifying neuropathic pain.

Cost of Chronic and Episodic Migraine. A pilot study from a tertiary headache centre in northern Italy.

BACKGROUND: Chronic migraine (CM) has a high impact on functional performance and quality of life (QoL). CM also has a relevant burden on the National Health Service (NHS), however precise figures are lacking. In this pilot study we compared the impact in terms of costs of CM and episodic migraine (EM) on the individual and on the National Health System (NHS). Furthermore, we comparatively evaluated the impact of CM and EM on functional capability and on QoL of sufferers. METHODS: We enrolled 92 consecutive patients attending the Pavia headache centre: 51 subjects with CM and 41 with episodic migraine (EM). Patients were tested with disability scales (MIDAS, HIT-6, SF-36) and with an ad hoc semi-structured questionnaire. RESULTS: The direct mean annual cost (in euro) per patient suffering from CM was €2250.0 ± 1796.1, against €523.6 ± 825.8 per patient with EM. The cost loaded on NHS was €2110.4 ± 1756.9 for CM, €468.3 ± 801.8 for EM. The total economic load and the different sub-items were significantly different between groups (CM vs. EM p = 0.001 for each value). CM subjects had higher scores than EM for MIDAS (98.4 ± 72,3 vs 15.5 ± 17.7, p = 0.001) and for HIT-6 (66.1 ± 8.4 vs 58.7 ± 10.1, p = 0.001). The SF-36 score was 39.9 ± 14,74 for CM and 66.2 ± 18.2 for EM (p = 0.001). CONCLUSIONS: CM is a disabling condition with a huge impact on the QoL of sufferers and a significant economic impact on the NHS. The adequate management of CM, reverting it back to EM, will provide a dual benefit: on the individual and on the society.

Effects of CGRP receptor antagonism in nitroglycerin-induced hyperalgesia.

BACKGROUND: The release of calcitonin gene-related peptide (CGRP) from trigeminal nerves plays a central role in the pathophysiology of migraine and clinical evidence shows an antimigraine effect for CGRP receptor antagonists. Systemic administration of nitroglycerin (NTG), a nitrovasodilator, consistently provokes spontaneous-like migraine attacks in migraine sufferers; in the rat, systemic NTG induces a condition of hyperalgesia, probably through the activation of cerebral/spinal structures involved in nociceptive transmission. AIM: The aim of this article is to test the analgesic effect of the CGRP receptor antagonist MK-8825 in two animal models of pain that may be relevant for migraine: the tail flick test and the formalin test performed during NTG-induced hyperalgesia. RESULTS: MK-8825 showed analgesic activity when administered alone at both the tail flick test and the formalin test. Furthermore, the CGRP antagonist proved effective in counteracting NTG-induced hyperalgesia in both tests. MK-8825 indeed reduced the nociceptive behavior when administered either simultaneously or prior to (30-60 minutes before) NTG. CONCLUSION: These data suggest that MK-8825 may represent a potential therapeutic tool for the treatment of migraine.

Combination of anti-CGRP/CGRP-R mAbs with onabotulinumtoxin A as a novel therapeutic approach for refractory chronic migraine: a retrospective study of real-world clinical evidence and a protocol for a double-blind, randomized clinical trial to establish the efficacy and safety.

Chronic migraine is a disabling neurovascular disorder that ranks amongst the top causes of years lived with disability worldwide. The duration and the frequency of migraine affect cognitive and affective domains, inducing worsening of memory, executive functions, orientation and causing anxiety. Population-based studies report a worrying level of resistance to treatments. Therefore, this study aims: 1) to assess efficacy of monoclonal antibodies (mAbs) directed towards the calcitonin gene-related peptide (CGRP) or its receptor (CGRP-R) for chronic migraine resistant to current preventatives; 2) to design a clinical trial protocol to evaluate the efficacy and safety of combination therapy utilizing anti-CGRP/CGRP-R together with onabotulinumtoxin A in patients suffering from resistant chronic migraine; 3) to provide a molecular rationale for combination therapy. A controlled trial is warranted as pooled analysis of real-world data from our group highlighted that combined treatment provides ≥50% reduction vs. baseline (onabotulinumtoxin A) of monthly headache days (MHDs) in up to 58.8% of patients, but there has been only sparse application of this combined therapy to date. The mAbs chosen are: erenumab, because its combination effect with onabotulinumtoxin A improved symptoms in 65% of patients; eptinezumab, due to its faster action. The results highlight that early diagnosis of migraine improves therapeutic outcomes with mAbs alone, confirming their effectiveness and the need for an adequately powered clinical trial evaluating the safety and potential superior effectiveness of eptinezumab/erenumab and onabotulinumtoxin A together.

Pain and agitation treatment in severe dementia patients: The need for Italian Mobilization-Observation-Behavior-Intensity-Dementia (I-MOBID2) pain scale translation, adaptation and validation with psychometric testing.

The 97% of dementia patients develops fluctuant neuropsychiatric symptoms often related to under-diagnosed and unrelieved pain. Up to 80% severe demented nursing home residents experiences chronic pain due to age-related comorbidities. Patients lacking self-report skills risk not to be appropriately treated for pain. Mobilization-Observation-Behavior-Intensity-Dementia (MOBID2) is the sole pain scale to consider the frequent co-occurrence of musculoskeletal and visceral pain and to unravel concealed pain through active guided movements. Accordingly, the Italian real-world setting can benefit from its translation and validation. This clinical study provides a translated, adapted and validated version of the MOBID2, the Italian I-MOBID2. The translation, adaptation and validation of the scale for non-verbal, severe demented patients was conducted according to current guidelines in a cohort of 11 patients over 65 with mini-mental state examination ≤ 12. The I-MOBID2 proves: good face and scale content validity index (0.89); reliable internal consistency (Cronbach's α = 0.751); good to excellent inter-rater (Intraclass correlation coefficient, and test-retest (ICC = 0.902) reliability. The construct validity is high (Rho = 0.748 p < 0.05 for 11 patients, Spearman rank order correlation of the overall pain intensity score with the maximum item score of I-MOBID2 Part 1; rho=0.895 p < 0.01 for 11 patients, for the overall pain intensity score with the maximum item score of I-MOBID2 Part 2) and a good rate of inter-rater and test-retest agreement was demonstrated by Cohen's K = 0.744. The average execution time is of 5.8 min, thus making I-MOBID2 a useful tool suitable also for future development in community setting with administration by caregivers.

A basic diagnostic headache diary (BDHD) is well accepted and useful in the diagnosis of headache. a multicentre European and Latin American study.

AIMS: We tested the usability and usefulness of the basic diagnostic headache diary (BDHD) for the diagnosis of migraine, tension-type headache and medication-overuse headache in European and Latin American countries. METHODS: Patients were subdivided into two groups according to a 1:1 randomization list. Those in group 1 were sent the BDHD before their first visit to the headache centre and asked to complete it for at least 1 month. Those in group 2 made their first visit to the headache centre without receiving the BDHD. RESULTS: A total of 626 patients from nine countries and 16 centres completed the study. The BDHD entries were complete in 97.5% of cases. BDHD information and clinical interview were, when taken together, considered complete for diagnosis in 97.7% of cases in group 1 whereas the information obtained by clinical interview alone in group 2 was considered complete in only 86.8% of cases (p < 0.001). The median number of diagnoses per patient in group 1 was significantly higher than in group 2 (p = 0.04). The BDHD was very well accepted by both patients and doctors. CONCLUSIONS: It is concluded that the BDHD is a useful tool in the diagnostic assessment of the most frequent and disabling forms of primary headache and in headache management.

Neurophysiological tests and neuroimaging procedures in non-acute headache (2nd edition).

BACKGROUND AND PURPOSE: A large number of instrumental investigations are used in patients with non-acute headache in both research and clinical fields. Although the literature has shown that most of these tools contributed greatly to increasing understanding of the pathogenesis of primary headache, they are of little or no value in the clinical setting. METHODS: This paper provides an update of the 2004 EFNS guidelines and recommendations for the use of neurophysiological tools and neuroimaging procedures in non-acute headache (first edition). Even though the period since the publication of the first edition has seen an increase in the number of published papers dealing with this topic, the updated guidelines contain only minimal changes in the levels of evidence and grades of recommendation. RESULTS: (i) Interictal EEG is not routinely indicated in the diagnostic evaluation of patients with headache. Interictal EEG is, however, indicated if the clinical history suggests a possible diagnosis of epilepsy (differential diagnosis). Ictal EEG could be useful in certain patients suffering from hemiplegic or basilar migraine. (ii) Recording evoked potentials is not recommended for the diagnosis of headache disorders. (iii) There is no evidence warranting recommendation of reflex responses or autonomic tests for the routine clinical examination of patients with headache. (iv) Manual palpation of pericranial muscles, with standardized palpation pressure, can be recommended for subdividing patient groups but not for diagnosis. Pain threshold measurements and EMG are not recommended as clinical diagnostic tests. (v) In adult and pediatric patients with migraine, with no recent change in attack pattern, no history of seizures, and no other focal neurological symptoms or signs, the routine use of neuroimaging is not warranted. In patients with trigeminal autonomic cephalalgia, neuroimaging should be carefully considered and may necessitate additional scanning of intracranial/cervical vasculature and/or the sellar/orbital/(para)nasal region. In patients with atypical headache patterns, a history of seizures and/or focal neurological symptoms or signs, MRI may be indicated. (vi) If attacks can be fully accounted for by the standard headache classification (IHS), a PET or SPECT scan will normally be of no further diagnostic value. Nuclear medical examinations of the cerebral circulation and metabolism can be carried out in subgroups of patients with headache for the diagnosis and evaluation of complications, when patients experience unusually severe attacks or when the quality or severity of attacks has changed. (vii) Transcranial Doppler examination is not helpful in headache diagnosis. CONCLUSION: Although many of the examinations described in the present guidelines are of little or no value in the clinical setting, most of the tools, including thermal pain thresholds and transcranial magnetic stimulation, have considerable potential for differential diagnostic evaluation as well as for the further exploration of headache pathophysiology and the effects of pharmacological treatment.

Alien hand syndrome in left posterior stroke.

Alien hand syndrome is a rare neurological disorder characterized by involuntary and uncontrollable motor behaviour, usually of an arm or hand. The patient perceives the affected limb as alien, and may personify it. The case of a 61-year-old right-handed woman who developed right posterior AHS after ischaemic stroke in the left posterior cerebral artery territory is reported. Neuroimaging studies disclosed no frontal or parietal involvement, while a posterior thalamic lesion was detected. A possible role of the thalamus in the genesis of AHS is discussed.

Walking strategies of visually impaired people on trapezoidal- and sinusoidal-section tactile groundsurface indicators.

The visual system in walking serves to perceive feedback or feed-forward signals. Therefore, visually impaired persons (VIP) have biased motor control mechanisms. The use of leading indicators (LIs) and long canes helps to improve their walking efficiency. The aims of this study were to compare the walking efficiency of VIP on trapezoidal- and sinusoidal-section LIs using an optoelectronic motion analysis system. VIP displayed a significantly longer stance phase, a shorter swing phase and shorter step and stride lengths when they walked on the sinusoidal LI than when they walked on the trapezoidal LI. Compared with the trapezoidal LI, VIP walking on the sinusoidal LI displayed significantly lower joint ranges of motion. The centre of mass lateral displacement was wider for VIP walking on the sinusoidal LI than on the trapezoidal LI. Some significant differences were also found in sighted persons walking on both LIs. In conclusion, the trapezoidal shape enabled visually impaired subjects to walk more efficiently, whereas the sinusoidal shape caused dynamic balance problems. STATEMENT OF RELEVANCE: These findings suggest that VIP can walk more efficiently, with a lower risk of falls, on trapezoidal-section than on sinusoidal-section LIs. These results should be considered when choosing the most appropriate ground tactile surface indicators for widespread use.

[Walking efficiency of blind people on trapezoidal and sinusoidal section tactile leading indicators]. / L'efficienza del cammino di soggetti non vedenti su piste tattili trapezoidali e sinusoidali.

Gait of visually impaired subjects (VIS) is worse than that of sighted ones. VIS can use tactile ground surface indicators to optimize their walking efficiency. Aim of the study was to compare VIS walking efficiency on either trapezoidal and sinusoidal shape leading indicators. VIS walking on the sinusoidal leading indicators showed a worsening of the time-distance parameters (a longer stance phase, a shorter swing phase and shorter step and stride lengths), reduced lower limb joint excursions and increased center of mass oscillations. In conclusion sinusoidal tactile indicators induce a stiffening of joints and a loss of balance with an increased risk of fall.

Anodal transcranial direct current stimulation in chronic migraine and medication overuse headache: A pilot double-blind randomized sham-controlled trial.

OBJECTIVES: Little evidence is available on the role of transcranial direct current stimulation (tDCS) in patients affected by chronic migraine (CM) and medication overuse headache (MOH). We aim to investigate the effects of tDCS in patients with CM and MOH as well as its role on brain activity. METHODS: Twenty patients with CM and MOH were hospitalized for a 7-day detoxification treatment. Upon admission, patients were randomly assigned to anodal tDCS or sham stimulation delivered over the primary motor cortex contralateral to the prevalent migraine pain side every day for 5 days. Clinical data were recorded at baseline (T0), after 1 month (T2) and 6 months (T3). EEG recording was performed at T0, at the end of the tDCS/Sham treatment, and at T2. RESULTS: At T2 and T3, we found a significant reduction in monthly migraine days (p = 0.001), which were more pronounced in the tDCS group when compared to the sham group (p = 0.016). At T2, we found a significant increase of alpha rhythm in occipital leads, which was significantly higher in tDCS group when compared to sham group. CONCLUSIONS: tDCS showed adjuvant effects to detoxification in the management of patients with CM and MOH. The EEG recording showed a significant potentiation of alpha rhythm, which may represent a correlate of the underlying changes in cortico-thalamic connections. SIGNIFICANCE: This study suggests a possible role for tDCS in the treatment of CM and MOH. The observed clinical improvement is coupled with a potentiation of EEG alpha rhythm.

SUNCT syndrome with paroxysmal mydriasis: Clinical and pupillometric findings.

SUNCT syndrome (short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing) is a primary headache characterised by a high frequency of attacks associated with marked autonomic periocular signs and symptoms. Activation of the hypothalamus via the superior salivary nucleus is probably responsible for some of the autonomic involvement observed during SUNCT attacks. We describe a case of SUNCT with unusual autonomic features (e.g., mydriasis) and early onset. Pupillometric studies were performed both in a basal condition (without anisocoria) and after instillation of phenylephrine (a drug with direct sympathomimetic activity) and pilocarpine (a parasympathetic agonist). The findings in this patient seem to indicate involvement of the ocular sympathetic supply in SUNCT, responsible for the mydriasis, and seem to strengthen the possibility that the autonomic phenomena in this syndrome vary with different levels of pain severity.

Alterations of the endocannabinoid system in an animal model of migraine: evaluation in cerebral areas of rat.

Endocannabinoids are involved in the modulation of pain and hyperalgesia. In this study we investigated the role of the endocannabinoid system in the migraine model based on nitroglycerin-induced hyperalgesia in the rat. Male rats were injected with nitroglycerin (10 mg/kg, i.p.) or vehicle and sacrificed 4 h later. The medulla, the mesencephalon and the hypothalamus were dissected out and utilized for the evaluation of activity of fatty acid amide hydrolase (that degrades the endocannabinoid anandamide), monoacylglycerol lipase (that degrades the endocannabinoid 2-arachidonoylglycerol), and binding sites specific for cannabinoid (CB) receptors. The findings obtained show that nitroglycerin-induced hyperalgesia is associated with increased activity of both hydrolases and increased density of CB binding sites in the mesencephalon. In the hypothalamus we observed an increase in the activity of fatty acid amide hydrolase associated with an increase in density of CB binding sites, while in the medulla only the activity of fatty acid amide hydrolase was increased. Anandamide also proved effective in preventing nitroglycerin-induced activation (c-Fos) of neurons in the nucleus trigeminalis caudalis. These data strongly support the involvement of the endocannabinoid system in the modulation of nitroglycerin-induced hyperalgesia, and, possibly, in the pathophysiological mechanisms of migraine.

Sensitisation of spinal cord pain processing in medication overuse headache involves supraspinal pain control.

Medication overuse could interfere with the activity of critical brain regions involved in the supraspinal control of pain signals at the trigeminal and spinal level, leading to a sensitisation phenomenon responsible for chronic pain. We hypothesised that medication-overuse headache (MOH) patients might display abnormal processing of pain stimuli at the spinal level and defective functioning of the diffuse noxious inhibitory controls. We tested 31 MOH patients before (bWT) and after (aWT) standard inpatient withdrawal treatment, 28 episodic migraine (EM) patients and 23 healthy control subjects. We measured the threshold, the area and the temporal summation threshold (TST) of the nociceptive withdrawal reflex before, during and after activation of the diffuse noxious inhibitory controls by means of the cold pressor test. A significantly lower TST was found in both the MOH (bWT and aWT) and the EM patients compared with the controls, and in the MOH patients bWT compared with both the MOH patients aWT and the EM patients. In the MOH bWT patients the cold pressor test induced a TST increase significantly lower than that found in the MOH aWT, EM and control groups. Abnormal spinal cord pain processing and a decrease of the antinociceptive activity of the supraspinal structures in MOH patients can be hypothesised. These abnormalities could, in part, be related to the medication overuse, given that the withdrawal treatment was related to an improvement in the neurophysiological findings.

EFNS guideline on the treatment of tension-type headache - report of an EFNS task force.

BACKGROUND: Tension-type headache (TTH) is the most prevalent headache type and is causing a high degree of disability. Treatment of frequent TTH is often difficult. OBJECTIVES: To give evidence-based or expert recommendations for the different treatment procedures in TTH based on a literature search and the consensus of an expert panel. METHODS: All available medical reference systems were screened for the range of clinical studies on TTH. The findings in these studies were evaluated according to the recommendations of the EFNS resulting in level A, B or C recommendations and good practice points. RECOMMENDATIONS: Non-drug management should always be considered although the scientific basis is limited. Information, reassurance and identification of trigger factors may be rewarding. Electromyography (EMG) biofeedback has a documented effect in TTH, whilst cognitive-behavioural therapy and relaxation training most likely are effective. Physical therapy and acupuncture may be valuable options for patients with frequent TTH, but there is no robust scientific evidence for efficacy. Simple analgesics and non-steroidal anti-inflammatory drugs are recommended for the treatment of episodic TTH. Combination analgesics containing caffeine are drugs of second choice. Triptans, muscle relaxants and opioids should not be used. It is crucial to avoid frequent and excessive use of analgesics to prevent the development of medication-overuse headache. The tricyclic antidepressant amitriptyline is drug of first choice for the prophylactic treatment of chronic TTH. Mirtazapine and venlafaxine are drugs of second choice. The efficacy of the prophylactic drugs is often limited, and treatment may be hampered by side effects.

Medication overuse headache and applicability of the ICHD-II diagnostic criteria: 1-year follow-up study (CARE I protocol).

Medication overuse headache (MOH) is a growing problem worldwide and a challenge for clinicians and investigators. This study aims to contribute to the ongoing debate surrounding the classification of MOH. Applying the revised diagnostic criteria for MOH contained in the updated International Classification of Headache Disorders (ICHD-II), we enrolled 140 probable MOH (p-MOH) patients. They were submitted to an in-patient detoxification protocol and re-examined 2, 6 and 12 months later to confirm, or otherwise, the diagnosis of MOH and to observe the evolution of their headache. MOH diagnosis was confirmed 2 months after detoxification in 71% of patients, who reverted to an episodic headache pattern and stopped their drug overuse The overall clinical situation at 2 months closely reflected the 1-year trend. The 2-month period after drug withdrawal should be retained as a diagnostic criterion in the ICHD-II because it is useful not only as a diagnostic parameter, but also as predictor of a good outcome of 1-year drug withdrawal. In addition, the present findings point to the need for a more objective criterion to quantify headache frequency after drug withdrawal.