Triptan use in elderly over 65 years and the risk of hospitalization for serious vascular events.

BACKGROUND: Several studies have focused on the use of triptan and the risk of acute vascular events but the existence of such association is still debated and has never been quantified in patients over 65 years. To assess whether triptan use among older is associated with an increased risk of hospitalization for acute vascular events. METHODS: A propensity score-matched cohort study was designed using the French national health insurance database linked to hospital stays. Patients aged ≥ 65 years, newly treated by triptans between 2011 and 2014, were included… The primary event was hospitalization for an acute ischemic vascular event within de 90 days following triptan initiation. Association with triptan exposure was investigated through cox regression model, considering exposure at inclusion, and with exposure as a time-varying variable A case-crossover (CCO) and a self-controlled case series (SCCS) analyses were also conducted to address potential residual confounding. RESULTS: The cohort included 24, 774 triptan users and 99 096 propensity matched controls (mean (SD) age: 71 years (5.9), 74% of women). Within 90 days after cohort entry, 163 events were observed in the triptan group, and 523 in the control group (0.66% vs. 0.53%, adjusted hazard ratio (aHR) exposed/not exposed 1.25 95%CI [1.05-1.49]; aHR time-varying 8.74 [5.21-14.66]). The association was significant (CCO) for all events (adjusted odds ratio (aOR1.63 [1.22-2.19]) with a more consistent association with cerebral events (aOR 2.14 [1.26-3.63]). The relative incidence (RI) for all events was 2.13 [1.76-2.58] in the SCCS, for cardiac (RI: 1.67 [1.23-2.27]) and for cerebral events (RI: 3.20, [2.30-4.45]). CONCLUSION: The incidence of acute vascular events was low among triptan users. We found that triptan use among older may be associated with a low increased risk for acute vascular events, which may be more marked for cerebral events such as stroke, than for cardiac events.

Occipital Nerve Stimulation for Recurrent Trigeminal Neuralgia Without Occipital Pain.

OBJECTIVES: Trigeminal neuralgia (TN) is a severe, debilitating pain condition causing physical and emotional distress. Although the management of TN is well codified with medical and then surgical treatments, 15% to 30% of patients will experience intractable pain. Neuromodulation techniques have been scarcely used for refractory TN, with only small case series and short-term follow-up. MATERIALS AND METHODS: We conducted a retrospective study of patients treated with occipital nerve stimulation (ONS) for medically and surgically resistant TN without painful trigeminal neuropathy. The effectiveness of the ONS was evaluated using the Barrow Neurological Institute (BNI) pain score and the pain relief (0%-100%) at best and at last follow-up. RESULTS: Seven patients who have refractory TN were included. The mean age at ONS was 49 years. The mean pain duration was 8.6 years. The mean number of medical and surgical treatments before ONS was six and five, respectively. A percutaneous trial was performed in five of seven patients; all responded (pain relief > 40%), and four of five patients experienced pain recurrence after explantation. Eventually, six patients had a permanent ONS implantation. The average BNI pain score before implantation was V. The mean follow-up after implantation was 59 months. All patients reported an improvement after implantation. The average BNI score and mean pain relief at best were IIIa and 86.7%, respectively. At last follow-up, the average BNI score and mean pain relief were IIIa and 58.0%, respectively, with three patients experiencing pain recurrence. Adverse events were reported for four patients who required surgical revision for lead breakage (1), erosion (1), migration (1), or hardware-related discomfort (1). One patient finally underwent explantation because of infection. CONCLUSIONS: Although ONS is not validated in this indication, these results suggest that it can induce an improvement in TN recurring after several surgical treatments, and the benefit of the stimulation can be sustained in the long term. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT01842763.

The teaching of headache medicine in France: A questionnaire-based study.

BACKGROUND: The treatment of patients with headache represents an important part of a neurologist's activity. It requires sufficient training for neurology residents. In France, residents in neurology can complete this training by attending specialized consultations or by participating in a postgraduate training program called "Diplôme Inter-Universitaire Migraine et Céphalées" (DIUMC). OBJECTIVE: The objective of this cross-sectional study was to investigate the French residents' knowledge in headache medicine and the impact of different types of training in headache medicine that are available in France. METHODS: An anonymous survey was carried out among 548 French residents in neurology. RESULTS: The questionnaires of 121 residents (22.1%) were analyzed. Among them, 54.5% (66/121) had no complementary training apart from the internship (Group 1), 21.5% (26/121) had attended only specialized consultations (Group 2), and 24% (29/121) had participated in the DIUMC (Group 3). There was no difference between all groups regarding the knowledge of the prevalence of primary or chronic headaches. There was almost no difference between the groups in the management of episodic migraine. In contrast, the management of tension-type headache and chronic headache was better known by residents of Group 3 than residents of Group 1. In these two diseases, residents of Group 3 offered prophylactic treatment more often. Almost 29% of the residents (35/121) had read the French guidelines for the diagnosis and management of migraine. In Group 3, residents had read them significantly more often (1.6% in Group 1, 38.5% in Group 2 and 62.1% in Group 3, p < 0.001). CONCLUSION: This study shows the lack of knowledge among French neurology residents regarding headache medicine. It highlights the interest of specific training programs that could improve the practical and theoretical knowledge of future neurologists.

A retrospective observation on 105 patients with chronic cluster headache receiving indomethacin.

BACKGROUND: Indomethacin (IMC) as a prophylactic treatment is considered to be ineffective in cluster headache (CH). However, small series suggested the interest of IMC in CH. Some authors support that an IMC test is useful in all trigeminal autonomic cephalalgias. We described clinical features of IMC responders in a retrospective cohort of chronic cluster headache (CCH). METHODS: This single-center and retrospective study was conducted in a tertiary care specialist headache center in France. Patients were selected between January 2007 and December 2008. We included all patients fulfilling CCH criteria (ICHD-3-beta). Data were collected from medical records. We recorded all the prescriptions of IMC as a prophylactic treatment. Responders were defined by 50% reduction in attack frequency; complete response was defined by disappearance of the attacks. The non-responders must have received at least 100 mg daily during 7 days. RESULTS: The study consisted of 324 CCH, 121 female (37%) and 203 males (63%) with an average age at onset of 33.93 (± 14.71) years. Of the patients, 105 were treated with IMC. Thirty patients (29%) were responders. Thirty-four patients (32%) were non-responders. Responding status was undefined for 41 patients (39%). Twelve patients (11%) had a complete response. Responders were composed by 18 women (60%) and 12 men (40%) and had on average 44.89 (± 12.88) years. The minimal effective dose was 86.11 mg daily (± 48.72). DISCUSSION: This study shows the interest of IMC in CCH patients. We recommend an IMC test as a third-line treatment in CCH.

Occipital Nerve Stimulation for Refractory Chronic Cluster Headache: A Cost-Effectiveness Study.

INTRODUCTION: Occipital nerve stimulation (ONS) is proposed to treat refractory chronic cluster headache (rCCH), but its cost-effectiveness has not been evaluated, limiting its diffusion and reimbursement. MATERIALS AND METHODS: We performed a before-and-after economic study, from data collected prospectively in a nation-wide registry. We compared the cost-effectiveness of ONS associated with conventional treatment (intervention and postintervention period) to conventional treatment alone (preintervention period) in the same patients. The analysis was conducted on 76 rCCH patients from the French healthcare perspective at three months, then one year by extrapolation. Because of the impact of the disease on patient activity, indirect cost, such as sick leave and disability leave, was assessed second. RESULTS: The average total cost for three months was €7602 higher for the ONS strategy compared to conventional strategy with a gain of 0.07 quality-adjusted life-years (QALY), the incremental cost-effectiveness ratio (ICER) was then €109,676/QALY gained. The average extrapolated total cost for one year was €1344 lower for the ONS strategy (p = 0.5444) with a gain of 0.28 QALY (p < 0.0001), the ICER was then €-4846/QALY gained. The scatter plot of the probabilistic bootstrapping had 80% of the replications in the bottom right-hand quadrant, indicating that the ONS strategy is dominant. The average indirect cost for three months was €377 lower for the ONS strategy (p = 0.1261). DISCUSSION: This ONS cost-effectiveness study highlighted the limitations of a short-time horizon in an economic study that may lead the healthcare authorities to reject an innovative strategy, which is actually cost-effective. One-year extrapolation was the proposed solution to obtain results on which healthcare authorities can base their decisions. CONCLUSION: Considering the burden of rCCH and the efficacy and safety of ONS, the demonstration that ONS is dominant should help its diffusion, validation, and reimbursement by health authorities in this severely disabled population.

Severe migraine and its control: A proposal for definitions and consequences for care.

Currently many patients with severe migraine do not receive appropriate treatment and are never referred to specialist headache centres. On the other hand, specialist headache centres are frequently attended by patients whose migraines could be managed adequately in the community. One reason for this may be the absence of standardised definitions of migraine severity and control and of a treatment algorithm for orientating difficult-to-treat patients to specialist headache centres. Based on a review of the relevant literature and consensus meetings, proposals have been made for these items. We propose that migraine should be considered severe if headache frequency is at least eight migraine days per month or, if headaches are less frequent, the HIT-6 score is ≥60 or ≥50% of headaches require complete interruption of activity. The proposed definition of migraine control is defined on the basis of appropriate response to acute headache therapy and to preventative therapy. A treatment algorithm is proposed to assess migraine control regularly and to adapt therapy accordingly. These proposals may contribute to developing and testing strategies for management of severe disease with appropriate and effective preventive treatment strategies. With the anticipated introduction of new possibilities for migraine prevention in the near future, the time is ripe for a holistic approach to migraine management.

The outcomes of a second and third Gamma Knife radiosurgery for recurrent essential glossopharyngeal neuralgia.

INTRODUCTION: Gamma Knife radiosurgery (GKR) is a minimally invasive surgical option for drug-resistant essential glossopharyngeal neuralgia (GPN). The authors reviewed pain outcomes and complications in GPN patients who underwent a second or a third GKR for recurrent or persistent pain. METHODS: A retrospective review of all patients treated in a single center (Marseille, France) since 2004 was performed. Median prescribed dose was 85 Gy (range 70-90 Gy) at second GKR and 85 Gy at third GKR. Clinical outcome was evaluated using the Barrow Neurological Institute (BNI) scale. RESULTS: Six patients (4 males, 2 females) underwent second or third GKR. The median age was 70.2 years (range 64-83 years) at second GKR and 79.8 years at third GKR. No patient had any previous surgery but GKR. Five cases had a neurovascular conflict. Median follow-up period was 12 months (range 10-94 months) after second GKR and 16 months after third GKR. The median delay to initial pain freedom response was 30 days (range 3-120 days). One patient experienced pharyngeal hypoesthesia after second GKR. After a third GKR, up to 16 months, no side effects were encountered. At the last follow-up, 3 patients were BNI I, 2 were BNI IIIa, and one did not have any improvement. CONCLUSIONS: Second GKR resulted in pain reduction with low risk of additional morbidity. In patients unsuitable for microvascular decompression, GKR as a repeat or third treatment for intractable GPN is safe and effective. Third GKR was not associated with any side effects up to 16 months after the procedure.

Contribution of Otoacoustic Emissions for Diagnosis of Atypical or Recurrent Intracranial Hypotension. A Cases Series.

BACKGROUND: The diagnosis of spontaneous or post-traumatic intracranial hypotension mainly rely on clinical features and neuroimaging. In atypical presentations, other non-invasive tests are missing to support the diagnosis of intracranial hypotension. The assessment of otoacoustic emissions (OAE) shown interest to monitor intracranial pressure mainly in cases of intracranial hypertension. This non-invasive method was also assessed in response to pressure change after lumbar puncture. A few reports showed abnormal results of distortion product otoacoustic emissions (DPOAE) in cases of spontaneous or post-traumatic intracranial hypotension. We describe additional results in a series of intracranial hypotension cases. We discuss the interest of DPOAE assessment in atypical presentations of intracranial hypotension. We review the other non-invasive tests reported in literature. METHODS: We studied 4 atypical or recurrent cases of spontaneous or post-traumatic intracranial hypotension by recording OAE in sitting then supine position. RESULTS: Unilateral or bilateral abnormal changes of DPOAE were recorded in all cases, in response to postural test. These changes were present even in the absence of vestibular symptoms. CONCLUSION: The study of OAE may be a non-invasive tool for the diagnosis of spontaneous intracranial hypotension.

Gamma Knife radiosurgery for glossopharyngeal neuralgia: A study of 21 patients with long-term follow-up.

Objective Glossopharyngeal neuralgia (GPN) is a very rare condition, affecting the patient's quality of life. We report our experience in drug-resistant, idiopathic GPN, treated with Gamma Knife radiosurgery (GKRS), in terms of safety and efficiency, on a very long-term basis. Methods The study was opened, self-controlled, non-comparative and bicentric (Marseille and Lausanne University Hospitals). Patients treated with GKRS between 2003 and 2015 (models C, 4C and Perfexion) were included. A single 4-mm isocentre was positioned in the cisternal portion of the glossopharyngeal nerve, with a targeting based both on magnetic resonance imaging (MRI) and computed tomography (CT). The mean maximal dose delivered was 81.4 ± 6.7 Gy (median = 85 Gy, range = 60-90 Gy at the 100% isodose line). Results Twenty-one patients (11 women, 10 men) benefited from 25 procedures. The mean follow-up period was 5.2 ± 3 years (range = 0.9-12.1 years). Seventeen (81%) were initially pain-free after GKRS. At three months, six months and one year after radiosurgery, the percentage of patients with good outcome (BNI classes I to IIIA) was 87.6%, 100% and 81.8%, respectively. Ten cases (58.8%) from the initial pain-free ones had a recurrence, after a mean period of 13.6 ± 10.4 months (range = 3.1-36.6 months). Only three patients (14.2%) had recurrences (two for each one of them) requiring further surgeries. Three patients underwent a second GKRS procedure; one case needed a third GKRS. The former procedures were performed at 7, 17, 19 and 30 months after the first one, respectively. Furthermore, two patients needed additional interventions. At last follow-up, 17 cases (80.9%) were still pain-free without medication. The actuarial pain relief without new surgery was 83%. A transient complication (paraesthesia of the edge of the tongue) was seen in one case (4.8%). Conclusion GKRS is a valuable, minimally invasive, surgical alternative for idiopathic GPN, with a very high short- and long-term efficacy and without permanent complications. A quality imaging, including T2 CISS/Fiesta MRI and bone CT acquisitions for good visualisation of the nerve and the other bony anatomic landmarks, is essential for targeting accuracy and successful therapy.

Sneezing in Primary Headaches With Cranial Autonomic Symptoms: Pathophysiological Considerations. A Series of Case Reports.

OBJECTIVE: To report a case series of sneezing systematically occurring in two cases with migraine and cranial autonomic symptoms and two with cluster headache. BACKGROUND: Sneezing occurring systematically during cluster headache or migraine is a rare condition. Sneezing has been described as a specific trigger for migraine. METHODS: Case reports. CASE SERIES: We describe four patients with primary headaches, presenting systematic sneezing at a definite time of premonitory, postdromal, or headache phase. All of these headaches were associated with cranial autonomic symptoms. CONCLUSION: Sneezing is a symptom associated with primary headaches. The definite place of sneezing in these patients suggests a particular implication of hypothalamus in the pathophysiology of these cases.

Headache Characteristics and Clinical Features of Elderly Migraine Patients.

OBJECTIVE: To investigate the headache characteristics and clinical features of elderly migraine patients at a tertiary headache center. METHODS: We retrospectively reviewed 239 records of migraine patients, over the age of 64 at the first visit, who had migraine as defined by the International Classification of Headache Disorders 3rd edition (beta version) from 2006 to 2015 based on the Marseille registry at Timone Hospital. RESULTS: 13.8% (33/239) patients had migraine with aura only, 13.0% (31/239) had both diagnoses. Of the patients who presented with migraine with aura, 13.4% (32/239) presented with aura without headache. Unilateral pain location was reported by 58.6% (140/239) of patients and the throbbing type of pain was present in 50.2% (120/239) of our study group. Photo- and phonophobia were observed in 77.4% (185/239) and 79.5% (190/239) of patients. Seventy-nine out of 239 (30.1%) patients were found to have probable medication overuse. Within this group, 31.65% (25/79) overused triptan and 70.9% (56/79) overused combination analgesics. We found higher frequencies of migraine for patients whose age at onset of migraine was younger than 18 years, and low frequency migraine was reported more frequently in the later onset group (P = .0357). DISCUSSION: We assess the headache characteristics of elderly migraine patients who were seen at our tertiary headache center and report the high frequency of probable medication overuse headache in this study group. Finally, we suggest that age of onset is an important factor in the clinical profile of these patients.

Cyclic Vomiting Syndrome in Children.

PURPOSE OF REVIEW: Cyclic vomiting syndrome (CVS) is a misrecognized and probably underdiagnosed episodic syndrome associated with migraine, occurring preferentially in childhood. Attacks are stereotyped for each individual, with predictable periodicity. This review summarizes recent clinical and paraclinical observations in this syndrome, and current approaches in explorations and therapeutics. RECENT FINDINGS: Clinical phenotype during prodromal, vomiting, and recovery phases contains visceral and neuropsychological symptoms, but also cranial and systemic symptoms. Some clinical arguments as circadian or circannual periodicity suggest a chronobiological disease. Red flags in clinical presentation are proposed to distinguish other etiologies of recurrent gastrointestinal disturbances and guide paraclinical explorations. Functional magnetic resonance imaging in both CVS and migraine displayed diminished insular connectivity with the sensorimotor network, suggesting a common pathophysiology. Pathophysiology of CVS is not well defined, and there is probably a multifactorial origin. Distinction with other differential diagnoses is a challenge for clinicians. Further research, in particular with functional imaging, are required to define pathophysiology of CVS. Control trials are missing in pediatric population. Injectable or intranasal sumatriptan are often effective. For prophylaxis, amitriptyline, cyproheptadine, or propranolol are the most common treatments, depending on age and comorbidities. Non-pharmacologic measures as lifestyle modification also seem to be effective as preventive treatment.

Comparative tolerability of treatments for acute migraine: A network meta-analysis.

Introduction Migraine headache is a neurological disorder whose attacks are associated with nausea, vomiting, photophobia and phonophobia. Treatments for migraine aim to either prevent attacks before they have started or relieve attacks (abort) after onset of symptoms and range from complementary therapies to pharmacological interventions. A number of treatment-related adverse events such as somnolence, fatigue, and chest discomfort have previously been reported in association with triptans. The comparative tolerability of available agents for the abortive treatment of migraine attacks has not yet been systematically reviewed and quantified. Methods We performed a systematic literature review and Bayesian network meta-analysis for comparative tolerability of treatments for migraine. The literature search targeted all randomized controlled trials evaluating oral abortive treatments for acute migraine over a range of available doses in adults. The primary outcomes of interest were any adverse event, treatment-related adverse events, and serious adverse events. Secondary outcomes were fatigue, dizziness, chest discomfort, somnolence, nausea, and vomiting. Results Our search yielded 141 trials covering 15 distinct treatments. Of the triptans, sumatriptan, eletriptan, rizatriptan, zolmitriptan, and the combination treatment of sumatriptan and naproxen were associated with a statistically significant increase in odds of any adverse event or a treatment-related adverse event occurring compared with placebo. Of the non-triptans, only acetaminophen was associated with a statistically significant increase in odds of an adverse event occurring when compared with placebo. Overall, triptans were not associated with increased odds of serious adverse events occurring and the same was the case for non-triptans. For the secondary outcomes, with the exception of vomiting, all triptans except for almotriptan and frovatriptan were significantly associated with increased risk for all outcomes. Almotriptan was significantly associated with an increased risk of vomiting, whereas all other triptans yielded non-significant lower odds compared with placebo. Generally, the non-triptans were not associated with decreased tolerability for the secondary outcomes. Discussion In summary, triptans were associated with higher odds of any adverse event or a treatment-related adverse event occurring when compared to placebo and non-triptans. Non-significant results for non-triptans indicate that these treatments are comparable with one another and placebo regarding tolerability outcomes.

Occipital nerve stimulation improves the quality of life in medically-intractable chronic cluster headache: Results of an observational prospective study.

Background Occipital nerve stimulation (ONS) has been proposed to treat chronic medically-intractable cluster headache (iCCH) in small series of cases without evaluation of its functional and emotional impacts. Methods We report the multidimensional outcome of a large observational study of iCCH patients, treated by ONS within a nationwide multidisciplinary network ( https://clinicaltrials.gov NCT01842763), with a one-year follow-up. Prospective evaluation was performed before surgery, then three and 12 months after. Results One year after ONS, the attack frequency per week was decreased >30% in 64% and >50% in 59% of the 44 patients. Mean (Standard Deviation) weekly attack frequency decreased from 21.5 (16.3) to 10.7 (13.8) ( p = 0.0002). About 70% of the patients responded to ONS, 47.8% being excellent responders. Prophylactic treatments could be decreased in 40% of patients. Functional (HIT-6 and MIDAS scales) and emotional (HAD scale) impacts were significantly improved, as well as the health-related quality of life (EQ-5D). The mean (SD) EQ-5D visual analogic scale score increased from 35.2 (23.6) to 51.9 (25.7) ( p = 0.0037). Surgical minor complications were observed in 33% of the patients. Conclusion ONS significantly reduced the attack frequency per week, as well as the functional and emotional headache impacts in iCCH patients, and dramatically improved the health-related quality of life of responders.

Cyclic Vomiting Syndrome in Adults and Children: A Hypothesis.

OBJECTIVE: To see how patients' clinical descriptions compare to the third classification of International Classification of Headache Disorders (ICHD-III beta). BACKGROUND: CVS is an episodic syndrome associated with migraine. It is a rare disorder of childhood and adulthood. New criteria are proposed in the third classification of International Classification of Headache Disorders. METHODS: This study describes children and adults' CVS characteristics at a French tertiary-care center, according to the ICHD-II and ICHD-III beta criteria. Clinical features, and results of paraclinical tests were characterized. RESULTS: Fifteen patients were included: 8 adults, 2 children, and 5 adolescents. Familial history of migraine or CVS was respectively noticed in 12 and 4 patients. The duration of premonitory, emetic, and postdromal phases was evaluated from hours to days. Some symptoms described in theses phases are also described in migrainous population, with a comparable frequency. Cranial or systemic autonomic symptoms were respectively reported in 47% and 93%. Nine patients described a circadian periodicity, and six patients described a circannual periodicity. The predictable periodicity was from 1 week to 12 months. A brain perfusion SPECT showed an increased hypothalamic perfusion during emetic phase in one patient. CONCLUSIONS: CVS is a rare episodic syndrome associated with migraine. Some clinical features and paraclincal tests suggest a chronobiological disease.

The Very Long-Term Outcome of Radiosurgery for Classical Trigeminal Neuralgia.

BACKGROUND: Radiosurgery is one of the neurosurgical alternatives for intractable trigeminal neuralgia (TN). OBJECTIVE: Although acceptable short-/mid-term outcomes have been reported, long-term results have not been well documented. METHODS: We report the long-term results in 130 patients who underwent radiosurgery for classical TN and were subsequently monitored through at least 7 years (median = 9.9, range = 7-14.5) of follow-up. RESULTS: The median age was 66.5 years. A total of 122 patients (93.8%) became pain free (median delay = 15 days) after the radiosurgery procedure (Barrow Neurological Institute, BNI class I-IIIa). The probability of remaining pain free without medication at 3, 5, 7 and 10 years was 77.9, 73.8, 68 and 51.5%, respectively. Fifty-six patients (45.9%) who were initially pain free experienced recurrent pain (median delay = 73.1 months). However, at 10 years, of the initial 130 patients, 67.7% were free of any recurrence requiring new surgery (BNI class I-IIIa). The new hypesthesia rate was 20.8% (median delay of onset = 12 months), and only 1 patient (0.8%) reported very bothersome hypesthesia. CONCLUSIONS: The long-term results were comparable to those from our general series (recently published), and the high probability of long-lasting pain relief and rarity of consequential complications of radiosurgery may suggest it as a first- and/or second-line treatment for classical, drug-resistant TN.