Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.

ObjectiveWe conducted a nationwide case-control study in Sweden to test the hypothesis that specific clinical characteristics are associated with increased risk of sudden unexpected death in epilepsy (SUDEP).MethodsThe study included 255 SUDEP cases (definite and probable) and 1,148 matched controls. Clinical information was obtained from medical records and the National Patient Register. The association between SUDEP and potential risk factors was assessed by odds ratios (ORs) and 95% confidence intervals (CIs) and interaction assessed by attributable proportion due to interaction (AP).ResultsExperiencing generalized tonic-clonic seizures (GTCS) during the preceding year was associated with a 27-fold increased risk (OR 26.81, 95% CI 14.86–48.38), whereas no excess risk was seen in those with exclusively non-GTCS seizures (OR 1.15, 95% CI 0.54–48.38). The presence of nocturnal GTCS during the last year of observation was associated with a 15-fold risk (OR 15.31, 95% CI 9.57–24.47). Living alone was associated with a 5-fold increased risk of SUDEP (OR 5.01, 95% CI 2.93–8.57) and interaction analysis showed that the combination of not sharing a bedroom and having GTCS conferred an OR of 67.10 (95% CI 29.66–151.88), with AP estimated at 0.69 (CI 0.53–0.85). Among comorbid diseases, a previous diagnosis of substance abuse or alcohol dependence was associated with excess risk of SUDEP.ConclusionsIndividuals with GTCS who sleep alone have a dramatically increased SUDEP risk. Our results indicate that 69% of SUDEP cases in patients who have GTCS and live alone could be prevented if the patients were not unattended at night or were free from GTCS.

Our results suggest that MG shares risk factors with other autoimmune diseases, to a greater degree than MS, with a particular role of the HLA-B8-DR3 haplotype, especially amongst younger and female patients.

Objective:Since the last epidemiological review of NMO/NMOSD, 22 additional studies have been conducted. We systematically review the worldwide prevalence, incidence and basic demographic characteristics of NMOSD, and provide a critical overview of studies.Methods:PubMed, Ovid Medline and EMBASE using Medical Subject Headings and keyword search terms and reference lists of retrieved articles were searched from 1999 until August 2019. We collected data on the country; region; methods of case assessment and aquaporin-4 antibody (AQP4-Ab) test; study period; limitations; incidence (per 100,000 person-years); prevalence (per 100,000 persons); age-, sex-, and ethnic group-specific incidence or prevalence.Results:We identified 33 relevant articles. The results indicated the highest estimates of incidence and prevalence of NMOSD in Afro-Caribbean region [0.73/100 000 person-years (95% CI: 0.45-1.01) and 10/100 000 persons (95% CI: 6.8-13.2)]. The lowest incidence and prevalence of NMOSD were found in Australia and New Zealand [0.037/100 000 person-years (95% CI: 0.036-0.038) and 0.7/100 000 persons (95% CI: 0.66-0.74)]. There was prominent female predominance in adults and the AQP4-Ab seropositive subpopulation. Incidence and prevalence peaked in middle-aged adults. African ethnicity had the highest incidence and prevalence of NMOSD, whereas white Caucasian ethnicity had the lowest. No remarkable trend of incidence was described over time.Conclusion:NMOSD is a rare disease worldwide. Variations in prevalence and incidence have been described among different geographic areas and ethnicities. These are only partially explained by different study methods and NMO/NMOSD definitions, highlighting the need for specifically designed epidemiological studies to identify genetic effects and etiological factors.

Methods relying on death certificates underestimate SUDEP incidence. SUDEP risk has been underestimated especially in boys and in older people regardless of sex. Patients with psychiatric comorbidities, women in particular, are at increased SUDEP risk.

Eagle syndrome (symptoms associated with an elongated styloid process (SP)) is commonly divided into two presentations. First, the so-called classic Eagle syndrome where patients can present with unilateral sore throat, dysphagia, tinnitus, unilateral facial and neck pain and otalgia. Second, there is the vascular or stylocarotid form of Eagle syndrome in which the elongated SP is in contact with the extracranial internal carotid artery. We describe two cases of internal carotid artery dissection associated with an elongated SP. One is a patient with ischaemic stroke and another with transient ischaemic attacks caused by an elongated SP. A surgical resection of the SP was performed on the former patient. Both patients were treated with anticoagulation and recovered well. A literature search only revealed two prior descriptions of carotid dissection in the context of an elongated SP.

Sudden unexpected death in epilepsy (SUDEP) is a leading epilepsy-related cause of death. Researchers have highlighted the similarities between SUDEP and sudden infant death syndrome (SIDS), but perinatal risk factors such as those identified for SIDS have not been assessed previously for SUDEP. We conducted a population-based case-control study of 58 SUDEP individuals and 384 living epilepsy controls born after 1982, utilizing the Swedish Medical Birth Register together with other national health registers and individual medical records to examine if prenatal and perinatal factors are associated with SUDEP risk. We observed a 3-fold SUDEP risk increase for infants who were small for gestational age (SGA) (odds ratio [OR] 3.13; 95% confidence interval [CI] 1.05-9.30) and for those with an Apgar score of 0-6 compared to 9-10 at 10 min (OR 3.22; 95% CI 1.05-9.87). After adjusting for a number of known SUDEP risk factors, we observed that the Apgar score between 0 and 6 after 10 min had a 10-fold increased risk for SUDEP OR 10.37 (95% CI 1.49-72.01) and over a 2-fold risk for those born after the 40th gestational week (OR 2.42; 95% CI 1.03-5.65). The potential mechanisms linking low Apgar score, gestational age, and SGA to SUDEP risk remain to be explored.

Objective: We conducted a nationwide case-control study in Sweden to test the hypothesis that antiepileptic drugs (AEDs), mono- polytherapy, adherence, antidepressants, neuroleptics, beta-blockers, and statins are associated with sudden unexpected death in epilepsy (SUDEP) risk.Methods: Included were 255 SUDEP cases and 1148 matched controls. Information on clinical factors and medications came from medical records and the National Patient and Prescription Registers. The association between SUDEP and medications was assessed by odds ratios (OR) with 95% confidence intervals (CI) adjusted for potential risk factors including type of epilepsy, living conditions, co-morbidity and frequency of generalized tonic-clonic seizures (GTCS).Results: Polytherapy, especially taking three or more AEDs was associated with a substantially reduced risk of SUDEP (OR 0.31, 95% CI: 0.14-0.67). Combinations including lamotrigine (OR 0.55, 95% CI 0.31-0.97), valproic acid (OR 0.53, 95% CI: 0.29-0.98) and levetiracetam (OR 0.49, 95% CI 0.27-0.90) were associated with reduced risk. No specific AED was associated with increased risk. Regarding monotherapy, although limited numbers, the lowest SUDEP risk was seen in users of levetiracetam (0.10, 95% CI: 0.02-0.61). Having non-adherence mentioned in the medical record was associated with an OR of 2.75 (95% CI 1.58-4.78). Statin use was associated with a reduced SUDEP risk (OR 0.34, 95% CI: 0.11-0.99) but not SSRI use.Interpretation: These results provide support for the importance of medication adherence and intensified AED treatment for patients with poorly controlled GTCS in the efforts to reduce SUDEP risks and suggest that comedication with statins may reduce risks.