Impact on monthly migraine days of discontinuing anti-CGRP antibodies after one year of treatment - a real-life cohort study.

OBJECTIVE This study aims to analyse the effect of the discontinuation of anti-calcitonin gene-related peptide antibodies on monthly migraine days after 12 treatment months. BACKGROUND Anti-calcitonin gene-related peptide antibodies have been a game changer in migraine prophylaxis. However, high treatment costs warrant reducing treatment duration to the essential minimum. METHODS We collected data of patients with migraine who had received anti-calcitonin gene-related peptide antibodies and had received treatment for 12 months. RESULTS We included 52 patients. The average number of monthly migraine days was 16 ± 7 days at baseline, 6 ± 6 in the third, and 5 ± 4 in the 12th treatment month. After treatment interruption, the number of monthly migraine days was 6 ± 4 days in the first month, 9 ± 4 days in the second, and 11 ± 5 days in the third month. Most patients (88.9%) restarted treatment. CONCLUSION Only little of the therapeutic effect of anti-calcitonin gene-related peptide antibodies outlasts their pharmacological effect. After treatment interruption, migraine frequency rose in most patients, and prophylaxis was required again in most cases.Limiting treatment to benefitting patients and confirming the need for prophylaxis periodically is reasonable. However, our data does not support the need for prescheduled treatment discontinuation after 12 months and a fixed duration of the treatment interruption of 3 months

Swiss QUality of life and healthcare impact Assessment in a Real-world Erenumab treated migraine population (SQUARE study): interim results.

BACKGROUND The fully human monoclonal antibody erenumab, which targets the calcitonin gene-related peptide (CGRP) receptor, was licensed in Switzerland in July 2018 for the prophylactic treatment of migraine. To complement findings from the pivotal program, this observational study was designed to collect and evaluate clinical data on the impact of erenumab on several endpoints, such as quality of life, migraine-related impairment and treatment satisfaction in a real-world setting. METHODS An interim analysis was conducted after all patients completed 6 months of erenumab treatment. Patients kept a headache diary and completed questionnaires at follow up visits. The overall study duration comprises 24 months. RESULTS In total, 172 adults with chronic or episodic migraine from 19 different sites across Switzerland were enrolled to receive erenumab every 4 weeks. At baseline, patients had 16.6 ± 7.2 monthly migraine days (MMD) and 11.6 ± 7.0 acute migraine-specific medication days per month. After 6 months, erenumab treatment reduced Headache Impact Test (HIT-6™) scores by 7.7 ± 8.4 (p < 0.001), the modified Migraine Disability Assessment (mMIDAS) by 14.1 ± 17.8 (p < 0.001), MMD by 7.6 ± 7.0 (p < 0.001) and acute migraine-specific medication days per month by 6.6 ± 5.4 (p < 0.001). Erenumab also reduced the impact of migraine on social and family life, as evidenced by a reduction of Impact of Migraine on Partners and Adolescent Children (IMPAC) scores by 6.1 ± 6.7 (p < 0.001). Patients reported a mean effectiveness of 67.1, convenience of 82.4 and global satisfaction of 72.4 in the Treatment Satisfaction Questionnaire for Medication (TSQM-9). In total, 99 adverse events (AE) and 12 serious adverse events (SAE) were observed in 62 and 11 patients, respectively. All SAE were regarded as not related to the study medication. CONCLUSIONS Overall quality of life improved and treatment satisfaction was rated high with erenumab treatment in real-world clinical practice. In addition, the reported impact of migraine on spouses and children of patients was reduced. TRIAL REGISTRATION BASEC ID 2018-02,375 in the Register of All Projects in Switzerland (RAPS)

Swiss QUality of life and healthcare impact Assessment in a Real-world Erenumab treated migraine population (SQUARE study): interim results

BACKGROUND The fully human monoclonal antibody erenumab, which targets the calcitonin gene-related peptide (CGRP) receptor, was licensed in Switzerland in July 2018 for the prophylactic treatment of migraine. To complement findings from the pivotal program, this observational study was designed to collect and evaluate clinical data on the impact of erenumab on several endpoints, such as quality of life, migraine-related impairment and treatment satisfaction in a real-world setting. METHODS An interim analysis was conducted after all patients completed 6 months of erenumab treatment. Patients kept a headache diary and completed questionnaires at follow up visits. The overall study duration comprises 24 months. RESULTS In total, 172 adults with chronic or episodic migraine from 19 different sites across Switzerland were enrolled to receive erenumab every 4 weeks. At baseline, patients had 16.6 ± 7.2 monthly migraine days (MMD) and 11.6 ± 7.0 acute migraine-specific medication days per month. After 6 months, erenumab treatment reduced Headache Impact Test (HIT-6™) scores by 7.7 ± 8.4 (p < 0.001), the modified Migraine Disability Assessment (mMIDAS) by 14.1 ± 17.8 (p < 0.001), MMD by 7.6 ± 7.0 (p < 0.001) and acute migraine-specific medication days per month by 6.6 ± 5.4 (p < 0.001). Erenumab also reduced the impact of migraine on social and family life, as evidenced by a reduction of Impact of Migraine on Partners and Adolescent Children (IMPAC) scores by 6.1 ± 6.7 (p < 0.001). Patients reported a mean effectiveness of 67.1, convenience of 82.4 and global satisfaction of 72.4 in the Treatment Satisfaction Questionnaire for Medication (TSQM-9). In total, 99 adverse events (AE) and 12 serious adverse events (SAE) were observed in 62 and 11 patients, respectively. All SAE were regarded as not related to the study medication. CONCLUSIONS Overall quality of life improved and treatment satisfaction was rated high with erenumab treatment in real-world clinical practice. In addition, the reported impact of migraine on spouses and children of patients was reduced. TRIAL REGISTRATION BASEC ID 2018-02,375 in the Register of All Projects in Switzerland (RAPS)

Postlesional plasticity in central auditory processing:MRI and FMRI image registration and statistical signal processing

The most general and striking evidence related with brain injury is that of the restoration of function. Recovery of motor and somatosensory functions has shown to commonly occur after stroke, but not all individuals show improvement. Clinical studies have shown the capacity of pharmacological and rehabilitative interventions to accelerate and/or augment recovery after stroke. However, the mechanisms underlying the post-stroke brain functional reorganization, i.e., the brain plasticity, are still not well established. Therefore, therapeutic trials of agents or rehabilitative procedures targeting stroke recovery may benefit from brain mapping studies that may aid to better understand this functional reorganization. Thus the research aimed at the identification of the mechanisms underlying functional recovery should be given high priority, particularly with regard to environmental enrichment, rehabilitation and pharmacological interventions. Prior to investigation of post-stroke functional reorganization, two important conditions have to be gathered: having knowledge of the brain function under normal conditions, i.e., in normal subjects without brain lesions, and having devices adapted to study brain region of interest. This thesis addresses the post-stroke functional reorganization in auditory processing with a cross-sectional study in patients with unilateral hemispheric lesions and a longitudinal study in a patient with a lesion of a right acoustic radiation. Before performing these two studies with patients, normal function of the auditory processing is assessed and appropriate tools are developed. Audition is the key to language processing, the most important communication system in man. Hearing impairments arising from pathology of the brain injury may have detrimental consequences on the quality of the patient life, restricting our ability to interact with others, causing misunderstandings and fatigue, heightening stress and filtering out the myriad of sound experiences that give pleasure and meaning to life. The perception of an auditory scene in everyday acoustic environments involves identifying the content ("what") and the location ("where") of sound. Evidence indicates that sound recognition and sound localization are processed by at least partially independent anatomically distinct networks. In humans, activation studies have suggested existence of a ventral, temporo-frontal, "what" and dorsal, parieto-prefrontal, "where" pathways on the convexities. However, no studies have been able to clearly demonstrate "what" and "where" specialization in early stage auditory areas. This is mainly due to high local interindividual sulcal variability. Indeed, the precise realignment of anatomical landmarks on the supratemporal plane could not be achieved with current registration methods, thus providing less detailed and accurate functional maps. After a short introduction on brain variability, a brief description of auditory cortex structure and function is presented. High variability of the auditory cortex is a major problem when performing activation group studies. For this reason, the interindividual comparison of auditory activations necessitates appropriate method for brain superposition, i.e., brain registration. Two registration approaches are described, voxel-based and feature-based approaches, with demonstrating the benefit of feature-based approaches for interindividual superposition of highly variable cortical structures. Therefore we developed a local landmark-based registration algorithm. This algorithm mainly consisted in semi-automatical extraction of the sulci delimiting Heschl's gyrus and in their realignment, using thin-plate splines, with the corresponding landmarks of the reference brain. We employed this algorithm on "what" and "where" functional data in 18 normal subjects acquired with 1.5 Tesla MR scanner (from [1]) and 15 normal subjects acquired with 3 Tesla MR scanner. Our results have shown that a precise realignment of anatomical structures on the supratemporal plane yielded more detailed functional maps of a group of subjects, which were more consistent with cytoarchitectonically defined auditory areas, than widely used global non-rigid voxel-based registration methods. Moreover, our results demonstrated a specialization of anterior and anterior lateral auditory areas in sound recognition, and caudomedial and posterior auditory areas in sound localization. A first patient study performed on patients with unilateral hemispheric lesion compared "what" and "where" activations on the supratemporal plane between each patient and a group of normal subjects (both acquired with 1.5 Tesla). Our results demonstrated that a unilateral hemispheric lesion, left or right, disturbs auditory processing in both ipsilesional and contralesional hemispheres. This disruption of auditory processing may be an increase or decrease of activation patterns in an area known to be activated for conjoint activations by sound recognition and sound localization. Moreover, our results demonstrated that specialized networks were disturbed in patients with unilateral hemispheric lesions in two different ways: (i) changes in specialized task-related activations, and (ii) increase in specialized task-related networks in the intact hemisphere associated with normal performance in the corresponding task. In a second patient study that is a longitudinal study performed on a patient with a lesion of a right acoustic radiation, we investigated the effect of a unilateral subcortical lesion on the early cortical auditory processing within intact ipsilesional and contralesional hemispheres. Our results demonstrated the contralesional increase in activation of homologous auditory areas in the early stage of recovery, when auditory function was impaired, while at later stage the ipsilesional regions were more activated, as auditory function recovered

Impact on monthly migraine days of discontinuing anti-CGRP antibodies after one year of treatment - a real-life cohort study

OBJECTIVE This study aims to analyse the effect of the discontinuation of anti-calcitonin gene-related peptide antibodies on monthly migraine days after 12 treatment months. BACKGROUND Anti-calcitonin gene-related peptide antibodies have been a game changer in migraine prophylaxis. However, high treatment costs warrant reducing treatment duration to the essential minimum. METHODS We collected data of patients with migraine who had received anti-calcitonin gene-related peptide antibodies and had received treatment for 12 months. RESULTS We included 52 patients. The average number of monthly migraine days was 16 ± 7 days at baseline, 6 ± 6 in the third, and 5 ± 4 in the 12th treatment month. After treatment interruption, the number of monthly migraine days was 6 ± 4 days in the first month, 9 ± 4 days in the second, and 11 ± 5 days in the third month. Most patients (88.9%) restarted treatment. CONCLUSION Only little of the therapeutic effect of anti-calcitonin gene-related peptide antibodies outlasts their pharmacological effect. After treatment interruption, migraine frequency rose in most patients, and prophylaxis was required again in most cases.Limiting treatment to benefitting patients and confirming the need for prophylaxis periodically is reasonable. However, our data does not support the need for prescheduled treatment discontinuation after 12 months and a fixed duration of the treatment interruption of 3 months

Disownership of body parts as revealed by a visual scale evaluation. An observational study

The disownership of body parts, that most frequently occurs on the left side of the body, contralateral to right-hemispheric lesions, is an infrequent disorder, as usually assessed by interviews asking for dichotomic "yes/no" responses. This observational study in right-brain-damaged stroke patients investigated the efficacy of a continuous Visual Analog Scale (VAS) to detect body disownership after right brain damage, compared to dichotomic questions. Thirty-two right-handed right-brain-damaged stroke patients were given a Standardized Interview (SI), asking "Whose hand/arm/leg is this?", followed by a VAS (asking patients to mark on a vertical line their agreement with the statement that a body part belonged to them). The neural correlates of this disorder and measures of extra-personal and personal spatial neglect were also assessed. Control data were recorded from 18 neurologically unimpaired right-handed participants. During the interview, no patient showed disownership of body parts. Conversely, on the VAS eight out of 32 (25%) patients' scores, but none of the controls' scores, indicated a judgement of disownership for left body parts, with a left-right difference larger than that of control participants. VAS-detected disownership was not systematically associated with extra-personal and personal unilateral spatial neglect. Lesion sites associated with disownership of left body parts included the caudate nucleus and the anterior part of the internal capsule. To conclude, the VAS task, compared to the interview, is a novel tool to detect disownership of left body parts in right brain-damaged patients. A revised classification of body-ownership disorders is proposed. The present variant, assessed and detected by the VAS task, is termed Covert disownership and distinguished from the Overt disownership assessed by a SI