Monoclonal antibodies against CGRP (R): non-responders and switchers: real world data from an austrian case series.

OBJECTIVE: Assessement of the responder and non-responder rate to consecutive monoclonal CGRP-antibody (CGRP-mAb) treatment, the presence of side effects, analysis of predictors of response and loss-of-effectiveness evaluation over time. METHODS: We conducted a retrospective analysis including 171 patients with episodic (EM) or chronic migraine (CM), who received one, two or three different CGRP-mAbs. Non-response was defined as ≤ 50% reduction of monthly migraine days (MMDs) in EM and ≤ 30% reduction of MMDs in CM after 3 months of treatment. RESULTS: 123 (71.9%) responded to the first mAb. Side effects led to treatment discontinuation in 9 (5.3%) patients. Of the 26 patients who did not respond to the first mAb or experienced a loss of efficacy over time, 11 (42.3%) responded to the second and two (28.6%) of 7 to the third monoclonal antibody. Poor response to therapy was associated with a higher monthly migraine frequency (p = 0.028), a higher number of prior preventive migraine therapies (p = 0.011) and medication overuse (p = 0.022). CONCLUSION: Our findings support mAb-class switch in non-responders or in patients experiencing a loss of effectiveness. The use of a third CGRP-mAb could be beneficial for some patients.

Primary headache types in adult epilepsy patients.

BACKGROUND: Headache is among the most common comorbidities in epilepsy. This study examined the distribution of different primary headache disorders in a large cohort of patients with diagnosed epilepsy. Headache types were analysed with regard to gender, type of epilepsy and antiepileptic drugs (AEDs). METHODS: In this prospective single-centre study, 500 patients with epilepsy (250 female, mean age: 45.52 ± 17.26 years) were evaluated with regards to primary headache types using a validated German headache questionnaire categorizing for migraine (MIG), tension-type headache (TTH) or trigeminal autonomic cephalalgias (TAC), their combinations and unclassifiable headache. Data regarding type of epilepsy, seizure-associated headache, AED treatment and seizure freedom were collected. RESULTS: Of 500 patients with epilepsy, 163 (32.6%) patients (108 female and 55 male) reported suffering from headaches at least 1 day per month. MIG (without aura, with aura) and TTH were the most frequent headache type (MIG 33.1%, TTH 33.1%). Female epilepsy patients reported headaches significantly more often than male patients (x2 = 8.20, p = 0.0042). In contrast, the type of epilepsy did not significantly affect headache distribution. Of 163 patients with headache, 66 (40.5%) patients reported seizure-associated headache and AEDs were used by 157 patients. Of importance, patients with AED monotherapy suffered from MIG less often when compared to patients on polytherapy (x2 = 4.79, p = 0.028). CONCLUSION: MIG and TTH are the most common headache types in epilepsy patients and headache is more frequent among female epilepsy patients. Monotherapy in AEDs might have a beneficial effect on the frequency of headache compared to polytherapy.

Hypoxia-related mechanisms inducing acute mountain sickness and migraine.

Experimental models of human diseases are vital for pathophysiological and therapeutic research. To investigate the initiation, maintenance, pathophysiology and even termination of a migraine/headache attack these models are urgently needed. Results from different studies promote the profound involvement of hypoxia in migraine and other primary/secondary headaches. The possible mechanisms that drive the induction of headaches through hypoxia are still unknown, but several modes of action, such as increased blood flow, dilation of cerebral arteries, the release of nitroglycerin, calcitonin gene-related peptide and adenosine or increased oxygen extraction are discussed intensively. In studies exposing healthy volunteers and people with a history of migraine to controlled normobaric hypoxia, our research group could demonstrate normobaric hypoxia to be an effective trigger of migraine headaches. Furthermore, a longitudinal measurement of calcitonin gene-related peptide (CGRP), during a hypoxic challenge in migraine patients, revealed increasing CGRP levels with prolonged hypoxic challenge. Since GRP has been linked to migraine and other headache disorders, hypoxia could be regarded as initiator for headaches on a neurotransmitter basis. Furthermore, it has been known for more than 2 decades from studies in vitro and in vivo that hypoxia can induce cortical spreading depression, a phenomenon believed to represent aura. Considering the increased prevalence of migraine in altitude populations and the solid pathophysiological changes on cellular and neurotransmitter level-the role of hypoxia should be investigated in greater detail by the headache community.

Investigating the Migraine Cycle over 21 Consecutive Days Using Proton Magnetic Resonance Spectroscopy and Resting-State fMRI: A Pilot Study.

Recent neuroimaging studies have revealed important aspects of the underlying pathophysiological mechanisms of migraine suggesting abnormal brain energy metabolism and altered functional connectivity. Proton magnetic resonance spectroscopy (1H-MRS) studies investigated migraine patients in the interictal or ictal state. This first-of-its-kind study aimed to investigate the whole migraine cycle using 1H-MRS and resting-state functional magnetic resonance imaging (fMRI). A migraine patient underwent 1H-MRS and resting-state fMRI for 21 consecutive days, regardless of whether he was in an interictal or ictal state. Metabolite ratios were assessed and compared to the intrinsic connectivity of subcortical brain areas. Probable migraine phase-dependent changes in N-acetyl aspartate (NAA)/total creatine (tCr) and choline (Cho)/tCr levels are found in the left occipital lobe and left basal ganglia. NAA reflects neuronal integrity and Cho cellular membrane turnover. Such abnormalities may increase the susceptibility to excitatory migraine triggers. Functional connectivity between the right hippocampus and right or left pallidum was strongly correlated to the NAA/Cho ratio in the right thalamus, suggesting neurochemical modulation of these brain areas through thalamic connections. To draw statistically significant conclusions a larger cohort is needed.