More than 0.6 million people suffer from disabling migraines in Greece causing a dramatic work loss, but only a small proportion of migraineurs attend headache centres, most of them being treated by non-experts. On behalf of the Hellenic Headache Society, we report here a consensus on the diagnosis and treatment of adult migraine that is based on the recent guidelines of the European Headache Federation, on the principles of Good Clinical Practice and on the Greek regulatory affairs. The purposes are three-fold: (1) to increase awareness for migraine in Greece; (2) to support Greek practitioners who are treating migraineurs; and (3) to help Greek migraineurs to get the most appropriate treatment. For mild migraine, symptomatic treatment with high dose simple analgesics is suggested, while for moderate to severe migraines triptans or non-steroidal anti-inflammatory drugs, or both, should be administered following an individually tailored therapeutic strategy. A rescue acute treatment option should always be advised. For episodic migraine prevention, metoprolol (50–200 mg/d), propranolol (40–240 mg/d), flunarizine (5–10 mg/d), valproate (500–1800 mg/d), topiramate (25–100 mg/d) and candesartan (16–32 mg/d) are the drugs of first choice. For chronic migraine prevention topiramate (100-200 mg/d), valproate (500–1800 mg/d), flunarizine (5–10 mg/d) and venlafaxine (150 mg/d) may be used, but the evidence is very limited. Botulinum toxin type A and monoclonal antibodies targeting the CGRP pathway (anti-CGRP mAbs) are recommended for patients suffering from chronic migraine (with or without medication overuse) who failed or did not tolerate two previous treatments. Anti-CGRP mAbs are also suggested for patients suffering from high frequency episodic migraine (≥8 migraine days per month and less than 14) who failed or did not tolerate two previous treatments.
Background:Recent evidence suggests that patients with herpes simplex virus (HSV) encephalitis may relapse because of autoimmunity against the N-methyl-D-aspartate receptor (NMDAR). We present a case series of post-HSV relapsing encephalopathy associated with antibodies to central nervous system (CNS) synaptic antigens.Patient/Methods:Sera and cerebrospinal fluid (CSF) from five patients with HSV encephalitis who relapsed after antiviral therapy were tested for anti-NMDAR, gamma-aminobutyric acid b receptor (GABAbR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), Leucine-rich, glioma inactivated 1 (LGI1), anti -contactin-associated protein-like 2 (CASPR2) and dipeptidyl-peptidase-like protein-6 (DDPX) antibodies using cell-based assays.Results:Five patients (two infants, one child and two adults) developed post-HSV autoimmune encephalitis. The infants, aged 9 months and 10 months, after prompt and seemingly successful anti-HSV therapy, were readmitted with typical signs of NMDAR-encephalitis evolving within days, with NMDAR antibodies detected in both serum and CSF. Although they were promptly treated with intravenous immunoglobulin (IVIg) and with IVIg followed by rituximab, respectively, they were both left with psychomotor deficits. A 14-year-old girl with seizures due to HSV encephalitis improved with anti-HSV therapy. Later, she manifested intractable seizures and she was found positive for anti-NMDAR antibodies which persist. The two adults were women, aged 58 and 33 years. The first recovered after anti-HSV therapy and remained asymptomatic for 6 months, until she developed generalized seizures with persisting CSF anti-NMDAR antibodies; the second, who continued to be encephalopathic after 2 weeks of anti-HSV therapy, tested positive for anti-NMDAR antibodies in the serum and anti-GABAbR antibodies in the serum and CSF. She recovered fully following IVIg therapy but her serum anti-GABAbR antibodies persist 34 months later.Discussion:Infection of the CNS with HSV can trigger CNS autoimmunity associated not only with anti-NMDAR but also with anti-GABAbR antibodies. These antibodies can persist in the serum, even without associated symptoms, but their presence in the CSF is firmly associated with disease development. In contrast to children and adults who responded well to therapies, the infants had an incomplete recovery with severe psychomotor deficits probably due to the interference of anti-NMDAR antibodies with neuro-developmental processes.
Objective To estimate the prevalence, burden and current treatment of disabling primary headaches in a large sample of the Greek population aged 18–70 years old. Methods This is an observational descriptive study, with cross-sectional design performed by quantitative computer-assisted telephone interviews, using a validated 37-item questionnaire for headaches. The prevalence, burden, and current treatment of primary headaches (ICHD-3) were recorded along with participants’ treatment preferences. Results Out of 10,008 interviewed participants, 1197 (12.0%) reported headaches affecting performance. The annual prevalence of migraine was 8.1% (95% confidence interval, 7.6–8.7, corresponding to 0.6 million Greeks), of chronic migraine 1.0% (95% confidence interval, 0.8–1.2, corresponding to 0.1 million), and of tension-type headache 3.8% (95% confidence interval, 3.4–4.2, corresponding to 0.3 million). The participants with headaches reported 0.5 headache-induced lost workdays per month (corresponding to 5.8 million lost workdays annually) and reductions in performance on 2.8 workdays per month (corresponding to 30.9 million workdays annually). In all, 43.4% of headache participants felt bad/ashamed because of headaches and 21.9% sought professional treatment, most often from a private neurologist. 83.8% of headache participants had never taken pharmacological prophylaxis, and only 5.5% were currently under preventative treatment. For both prophylactic and acute treatment, headache participants prefer oral medication to injection or stimulation devices. Conclusion More than 10% of the Greek adult population up to 70 years old experience disabling headaches, causing a dramatic work loss. More than 80% of these have never taken pharmacological prophylaxis. Thus, enriching the quality of life of people with headaches relies crucially on expanding awareness about headaches and their treatment.
The confirmed involvement of the neuropeptide calcitonin gene-related peptide (CGRP) in the pathophysiology of migraine has led to the development of treatments, which for the first time are specific to migraine and mechanism based, in contrast to repurposed traditional prophylactic anti-migraine medications. Thus, in the last 5 years, the European Medicines Agency (EMA) approved four monoclonal antibodies that target either the CGRP ligand (eptinezumab, fremanezumab, and galcanezumab) or the CGRP receptor (erenumab). These anti-CGRP therapies are indicated for use in people with migraine who have more than 4 migraine days per month. In this consensus article, the Hellenic Headache Society highlights the indications and treatment protocols of these novel anti-migraine therapies, aiming to assist Greek neurologists in the optimal management of people with migraine. The recommendations are based on data from phase 3 randomized-controlled clinical trials, the recent European Headache Federation (EHF) recommendations, a consensus article under the auspices of both the EHF and the European Academy of Neurology (EAN), recent real-world evidence studies, and the authors’ acquired clinical experience.
Objective To estimate the prevalence and burden of medication overuse headache in a representative sample of the Greek population, aged 18–70 years old. Methods This is a cross-sectional descriptive observational study performed by quantitative computer-assisted telephone interviews, using a standardized 37-item questionnaire for headaches. The prevalence of medication overuse headache was estimated in the general population and compared within the groups formed by factors such as age, gender, diagnosis of headache type, prophylactic treatment used, geographical regions, social class, workdays lost and loss of productivity. Results 1197 (12.0%) participants reported headaches affecting performance out of 10,008 interviewees. The estimated prevalence of medication overuse headache in the general population was 0.7% (95% CI: 0.5–0.9). The female to male ratio was 3.6:1. The proportion of medication overuse headache was largest in the 35–54 age group, followed by the over 55 group. The Aegean islands and Crete were the regions with the highest proportion of medication overuse headache. Among participants with headaches, the proportion of medication overuse headache was 5.8% (95% CI: 4.4%–7.1%); 6.3% (95% CI: 4.7%–7.9%) among females and 4.4% (95% CI: 2.2%–6.6%) among males. In the same headache group, the proportion of medication overuse headache by prophylactic treatment for headache was 19.0% (95% CI: 9.5%–29.1%) for recipients and 5.0% (95% CI: 3.8–6.3) for non-recipients. The mean absenteeism in people with medication overuse headache was 1.0 days/month (95% CI: 0.4–1.6) and the mean presenteeism 6.3 days/month (95% CI: 3.9–8.7). The social class stratification showed a significant effect between the medication overuse headache in the sample of the general population and the C2 class, corresponding to skilled manual labour (OR: 0.7, CI: 0.5–0.9). In people with chronic migraine, and chronic tension type headache, as differentiated by the 37-item questionnaire, the proportion of medication overuse headache in the headache group estimated to be 50.5% (95% CI: 40.8%–60.1%) and 45.9%, (95% CI: 29.9%–62.0%) respectively. The group of people with acute headache medication overuse fulfilling the rest of the diagnostic criteria for medication overuse headache, except from the number of headache days per month (≥15 days/month), had a prevalence of 2.0% (95% CI: 1.75–2.30) and a proportion of 17.0% (95% CI: 14.8%–19.1%) among people with headache. In the episodic types of headache, the proportion of acute headache medication overuse was higher in the subgroup of people with high frequency episodic migraine, 24.9% (95% CI: 18.8%–31.0%), while it was 10.8% (95% CI: 8.2%–13.5%), for the low frequency episodic migraine and 8.5% (95% CI: 5.5%–10.4%), for the episodic tension type headache. Conclusion The prevalence of medication overuse headache in the general population in Greece and its proportion among the people with headache belongs to the lower part of the range of the reported literature, while the 3.6:1 female to male ratio is in agreement with it. In the same line, the impact of absenteeism and presenteeism on the workplace renders the condition alarming socio-economic health problem demanding immediate health policy planning.
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