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.

Ketamine-Magnesium for Refractory Chronic Cluster Headache: A Case Series.

OBJECTIVES: To evaluate the safety and efficacy of ketamine-magnesium combination to reduce attacks in a series of patients with refractory chronic cluster headache (rCCH). BACKGROUND: Refractory chronic cluster headache (CCH) is a rare but highly debilitating condition that needs new treatment options. A previous publication reported that a single infusion of ketamine-magnesium combination was effective in 2 patients with rCCH. METHODS: The treatment was proposed to consecutive patients with rCCH seen in 2 French hospitals between November 2015 and February 2020 and who were resistant to at least 3 preventive treatments. They received a single ketamine infusion (0.5 mg/kg over 2 hours) combined with magnesium sulfate (3000 mg). The main outcome was a comparison of the number of daily attacks 2 weeks prior to the ketamine-magnesium infusion and 1 week after (on days 7 and 8). The second outcome was the percentage of responders (patients with ≥50% reduction in the frequency of daily attacks). Safety was assessed by the recording of adverse events during infusion. Descriptive statistics are presented as mean ± standard deviation. RESULTS: Seventeen patients (14 men), with an age of 35.2 ± 8.1 years, were included. They presented with CCH for 6.6 ± 4.3 years. The number of daily attacks decreased from 4.3 ± 2.4 before treatment to 1.3 ± 1.0 after treatment (difference: -3.1 (95% CI: -4.5 to -1.6), P < .001). Seventy six percent (13/17) were responders. Transient and mild sedation was reported by 7/17 patients (41.2%). CONCLUSIONS: The ketamine-magnesium combination seems an effective and well-tolerated therapy for rCCH. Placebo-controlled studies should be conducted to further confirm these findings.

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.

Laughing headache with giant pacchionian granulations.

Laughing is recognized as a provoking factor for headache, certainly underestimated among the general population and few cases have been published to date. We report a single case of severe headache, provoked almost exclusively by outbursts of laughing, where venous magnetic resonance imaging revealed the presence of giant Pacchioni granulations in both right and transverse sinuses. Reviewing published cases of laughing headache, we discuss possible mechanisms of pain and the role of giant Pacchionian granulations.

Long-Term Efficacy of Occipital Nerve Stimulation for Medically Intractable Cluster Headache.

BACKGROUND: Occipital nerve stimulation (ONS) has been proposed to treat refractory chronic cluster headache (rCCH) but its efficacy has only been showed in small short-term series. OBJECTIVE: To evaluate ONS long-term efficacy in rCCH. METHODS: We studied 105 patients with rCCH, treated by ONS within a multicenter ONS prospective registry. Efficacy was evaluated by frequency, intensity of pain attacks, quality of life (QoL) EuroQol 5 dimensions (EQ5D), functional (Headache Impact Test-6, Migraine Disability Assessment) and emotional (Hospital Anxiety Depression Scale [HAD]) impacts, and medication consumption. RESULTS: At last follow-up (mean 43.8 mo), attack frequency was reduced >50% in 69% of the patients. Mean weekly attack frequency decreased from 22.5 at baseline to 9.9 (P < .001) after ONS. Preventive and abortive medications were significantly decreased. Functional impact, anxiety, and QoL significantly improved after ONS. In excellent responders (59% of the patients), attack frequency decreased by 80% and QoL (EQ5D visual analog scale) dramatically improved from 37.8/100 to 73.2/100. When comparing baseline and 1-yr and last follow-up outcomes, efficacy was sustained over time. In multivariable analysis, low preoperative HAD-depression score was correlated to a higher risk of ONS failure. During the follow-up, 67 patients experienced at least one complication, 29 requiring an additional surgery: infection (6%), lead migration (12%) or fracture (4.5%), hardware dysfunction (8.2%), and local pain (20%). CONCLUSION: Our results showed that long-term efficacy of ONS in CCH was maintained over time. In responders, ONS induced a major reduction of functional and emotional headache-related impacts and a dramatic improvement of QoL. These results obtained in real-life conditions support its use and dissemination in rCCH patients.

Cluster headache during pregnancy: case report and literature review.

A 32-year-old pregnant woman presented with cluster headache (CH) during the third trimester of a normal pregnancy. Pure oxygen mask inhalation was ineffective, and intranasal lidocaine applications were realized associated with oral methylprednisolone, given at 1 mg per kg once daily. These treatments rendered the pain tolerable and the pregnancy went to its term with no consequence on the baby. This case of CH attack during pregnancy raises the issues of the influence of sexual hormonal changes in women with CH and the way to treat this disease in such circumstance. To date, there are no therapeutic guidelines available; this case suggests some possibilities.

One or several types of triptan overuse headaches?

BACKGROUND: Whereas the clinical features of pure triptan overuse headache (TOH) are well known, there are insufficient data regarding the semiological pattern of headaches when triptan overuse is associated with other types of medication overuse. OBJECTIVE: To investigate and compare the clinical characteristics of patients with pure TOH and those with medication overuse headaches associating triptan and other medication overuses (combined TOH). METHODS: This cross-sectional, observational study was conducted in 7 tertiary-care headache centers participating in the French Observatory of Migraine and Headaches. From 2004 to 2006, data from 163 patients with TOH were collected in face-to-face structured interviews (according to the International Classification of Headache Disorders, 2nd edition criteria). RESULTS: Eighty-two patients fulfilled criteria for pure TOH (pTOH patients) and 81 for combined TOH (cTOH) patients. Continuous headaches were reported in 76% of cTOH patients compared with 32% of pTOH patients. Significantly more frequent and severe headaches and more intense phono-/photophobia between attacks were noted in cTOH patients. More cTOH than pTOH patients reported a history of tension-type headaches and a long-standing history of chronic headaches. Finally, compared with pTOH patients, cTOH patients were characterized by stronger dependence on acute treatments of headaches according to the DSM-IV criteria. CONCLUSIONS: Combined therapy with analgesics and/or the total number of drug units taken per day may cause a shift from a pattern of clear-cut headache attacks in patients with pTOH toward more severe clinical presentation in patients with cTOH. These patients should receive more intensive prophylactic therapy and specific behavioral management.

Impact of a public sensitization campaign on migraine management in France.

Migraine is a common and frequently disabling condition. Nevertheless, many migraine sufferers do not consult for migraine, are not medically followed up and self-treat the attacks. "Tour de France of migraine" consisted of free-access conferences held in six large towns in France following a wide public information campaign. This sensitization campaign aimed at providing participants with educational information on migraine disease and on current therapies. Headache sufferers were then invited to respond to two consecutive questionnaires delivered at the end of the conferences and 3 months later to assess the influence of the information delivered on their migraine management. Tour de France of migraine recruited mainly severe migraine sufferers, most of whom had already consulted and were medically followed up. However, migraine management was often suboptimal in these subjects since most of them found their acute treatment of attacks ineffective and only few of them received a prophylactic treatment. Three months after the conferences, more than half of respondents had consulted for headaches. There was a significant improvement in migraine-related disability, as reflected by a significant decrease in mean Headache Impact Test 6-item score, which might have been related to the higher proportion of subjects receiving a prophylactic treatment of migraine. The Tour de France of migraine campaign revealed the difficulty in sensitizing migraine sufferers towards the necessity of being medically followed up. Mainly patients with severe migraine attended the conferences and derived clinical benefit from the educational program. Other strategies should be developed to reach a wider population of migraine sufferers.

Tubulovesicular structures are a consistent (and unexplained) finding in the brains of humans with prion diseases.

Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker disease (GSS) and Fatal Familial Insomnia (FFI) are slow neurodegenerative disorders classified as transmissible spongiform encephalopathies (TSEs) or prion diseases, which appear in sporadic, hereditary or environmentally acquired forms. Tubulovesicular structures (TVS) are ultrastructural particles of unknown origin and chemical composition found in the brains of both animal and human forms of transmissible spongiform encephalopathies or prion diseases. In this paper, we report the results of a search for TVS in a total of 13 cases of sporadic Creutzfeldt-Jakob disease, three cases of Gerstmann-Sträussler-Scheinker disease, two cases of Fatal Familial Insomnia, and individual cases of familial, iatrogenic, and variant CJD (vCJD). TVS were found in all but one sporadic and one familial case of CJD. As controls, we examined 15 cases of Alzheimer's disease (AD), two cases of Pick's disease, and one case of multiple system atrophy. TVS were not present in any of these cases. This study confirms the TSE-specificity of TVS, the morphology of which suggests a possible pathogenetic role and relationship to recently described virion-like arrays of 25nm particles in scrapie-infected tissue cultures.

Behavioral dependence in patients with medication overuse headache: a cross-sectional study in consulting patients using the DSM-IV criteria.

OBJECTIVE: The aim of this study was to assess behavioral dependence on migraine abortive drugs in medication-overuse headache (MOH) patients and identify the predisposing factors. BACKGROUND: It is common occurrence that MOH patients relapse after medication withdrawal. Behavioral determinants of medication overuse should therefore be identified in MOH patients. METHODS: This was a cross-sectional, multicenter study that included 247 MOH patients (according to International Classification of Headache Disorders, 2nd edition criteria) consulting in French headache specialty centers. Face-to-face interviews were conducted by senior neurologists using a structured questionnaire including the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria for the evaluation of dependence, Hospital Anxiety and Depression Scale for the evaluation of anxiety and depression, and 6-item short-form Headache Impact Test scale for the determination of functional impact. RESULTS: Most MOH patients had pre-existing primary migraine (87.4%) and current migraine-type headaches (83.0%). Treatments overused included triptans (45.8%), opioid analgesics alone or in combination (43.3% of patients), and analgesics (27.9%). Nonmigraine abortive substances (tobacco, caffeine, sedatives/anxiolytics) were overused by 13.8% of patients. Two-thirds of MOH patients (66.8%) were considered dependent on acute treatments of headaches according to the DSM-IV criteria. Most dependent MOH patients had migraine as pre-existing primary headache (85.7%) and current migraine-type headaches (87.9%), and most of them overused opioid analgesics. More dependent than nondependent MOH patients were dependent on psychoactive substances (17.6% vs 6.1%). Multivariate logistic analysis indicated that risk factors of dependence on acute treatments of headaches pertained both to the underlying disease (history of migraine, unilateral headaches) and to drug addiction (opioid overuse, previous withdrawal). Affective symptoms did not appear among the predictive factors of dependence. CONCLUSION: In some cases, MOH thus appears to belong to the spectrum of addictive behaviors. In clinical practice, behavioral management of MOH should be undertaken besides pharmacological management.

[Cluster headache and brain imagery]. / Algie vasculaire de la face : place de l'imagerie.

Cluster headache is defined on clinical international criteria developed by International Headache Society (IHS, 2013). The realization of a brain MRI with arterial angio-MRI is required according to the French recommendations (Donnet et al., 2014) based on recent the literature. Numerous causes or diseases can mimic typical or atypical AVF (Edvardsson, 2014). Identification of these causes allows an appropriate treatment in addition with symptomatic treatment.

Autophagy is a part of ultrastructural synaptic pathology in Creutzfeldt-Jakob disease: a brain biopsy study.

Ultrastructural correlates of synaptic and dendritic spines loss have never been studied in detail in human transmissible spongiform encephalopathies (TSEs)-Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker (GSS) disease and fatal familial insomnia (FFI). In this paper, we describe synaptic alterations as found in brain biopsies from Creutzfeldt-Jakob disease and fatal familial insomnia patients. Our material consisted of brain biopsies obtained by open surgery from one FFI case, one case of variant Creutzfeldt-Jakob disease (vCJD), seven cases of sporadic Creutzfeldt-Jakob disease (sCJD) and one case of iatrogenic (human growth hormone) Creutzfeldt-Jakob disease (iCJD). For electron microscopy, approximately 2mm(3) samples were immersion fixed in 2.5% glutaraldehyde for less than 24h, embedded in Epon and routinely processed. Grids were examined and photographed in a transmission electron microscope. The synaptic alterations were found constantly; in practically every brain biopsy they were frequent. The accumulation of different subcellular organelles (neuroaxonal dystrophy), dark synapses and branching cisterns were the most frequent findings while concentric arrays of membranes were only rarely found. Autophagic vacuoles are formed in many synapses in all categories of human transmissible encephalopathies. We conclude that synaptic autophagy contributes to overall synaptic loss in brains affected in prion diseases.

RNA extraction and RT-PCR procedures adapted for the detection of enterovirus sequences from frozen and paraffin-embedded formalin-fixed spinal cord samples.

Methods for detecting enterovirus RNA in both paraffin-embedded, formalin-fixed and frozen spinal cord sections from amyotrophic lateral sclerosis (ALS) patients were established. A proteinase K digestion following the deparaffinization procedure was required for the fixed spinal cord sections, whereas only one step of crushing in phosphate buffered saline was necessary for the frozen samples prior to the extraction of the RNA. With an optimized reverse transcription and PCR procedure, enterovirus RNA could be detected from frozen and fixed archival spinal cord samples.

Is migraine with cranial nerve palsy an ophthalmoplegic migraine?

Ophthalmoplegic migraine (OM) is a rare form of primary headache. Because of its rarity, only a few cases, mostly symptomatic, are reported. We analyse nine cases among 52 973 adults who suffer from headaches with an oculomotor palsy firstly considered as OM. The study was retrospective and multicentric in a database set up in France. The aim of our investigation was to describe the clinical and radiological aspects of these cases and to discuss the diagnosis of OM. We demonstrate that the characteristics of the headaches were identical to usual migraine without oculomotor nerve palsy for each case. The study emphasises the difficulty of the OM diagnosis even with the new IHS criteria because of the rarity of having all characteristics. A wide heterogeneity was noted in cranial imagery and blood tests. We suggest adding the code of probable OM in the IHS classification to increase the knowledge and detection of this type of headache. A biological blood test and an MRI are systematically required to help clinicians in their diagnosis and to exclude alternative aetiology of headache with palsy.

Increased detection of 14-3-3 protein in cerebrospinal fluid in Sporadic Creutzfeldt-Jakob Disease during the disease course.

Diagnosis of Creutzfeldt-Jakob Disease (CJD) is based on neurological signs associated with characteristic electroencephalographic activity or detection of 14-3-3 protein in cerebrospinal fluid. However, the time course of 14-3-3 protein release during sporadic CJD is unknown. We report two observations in which the level of the detected 14-3-3 protein increased significantly with time. These preliminary cases suggest that there may be an increased release of 14-3-3 protein during the course of CJD as already proven for iatrogenic CJD.

Orofacial dyskinesias in a patient with primary biliary cirrhosis: a clinicopathological case report and review.

We describe the pathological and clinical aspects, including video and radiological magnetic resonance imaging, of a case of chronic acquired hepatocerebral degeneration with orofacial dyskinesias in relation to a primary biliary cirrhosis. We provide a review of the literature on this subject.