Andreas R. Gantenbein

Grey matter changes associated with medication-overuse headache: correlations with disease related disability and anxiety.

Abstract Objectives. Medication-overuse headache (MOH) is associated with psychiatric comorbidities. Neurobiological similarities to substance dependence have been suggested. This study investigated grey matter changes, focussing on pain and reward systems. Methods. Using voxel-based morphometry, structural MRIs were compared between 29 patients with both, MOH and migraine, according to International Headache Society criteria, and healthy controls. The Migraine Disability Assessment (MIDAS) score was used. Anxiety and depression were screened for with the Hospital Anxiety and Depression Scale (HADS) and confirmed by a psychiatrist, using the Mini International Neuropsychiatric Interview. Results. Nineteen patients (66%) had a present or past psychiatric disorder, mainly affective (N = 11) and anxiety disorders (N = 8). In all patients a significant increase of grey matter volume (GMV) was found in the periaqueductal grey matter of the midbrain, which correlated positively with the MIDAS and the HADS-anxiety subscale. A GMV increase was found bilaterally in the thalamus, and the ventral striatum. A significant GMV decrease was detected in frontal regions including orbitofrontal cortex, anterior cingulate cortex, the left and right insula, and the precuneus. Conclusion. These findings are consistent with dysfunction of antinociceptive systems in MOH, which is influenced by anxiety. Dysfunction of the reward system may be a neurobiological basis for dependence in a subgroup of MOH patients.

Decrease of Gray Matter Volume in the Midbrain is Associated with Treatment Response in Medication-Overuse Headache: Possible Influence of Orbitofrontal Cortex

Patients with chronic daily headache and overuse of analgesics, triptans, or other acute headache compounds, are considered to suffer from medication-overuse headache (MOH). This implies that medication overuse is the cause of headache chronification. It remains a key question why only two-thirds of patients with chronic migraine-like headache and overuse of pain medication improve after detoxification, whereas the remainder continue to have chronic headache. In the present longitudinal MRI study, we used voxel-based morphometry to investigate gray matter changes related to medication withdrawal in a group of humans with MOH. As a main result, we found that only patients with significant clinical improvement showed a significant decrease of previously increased gray matter in the midbrain including periaqueductal gray matter and nucleus cuneiformis, whereas patients without improvement did not. Patients without treatment response had less gray matter in the orbitofrontal cortex. Another striking result is the correlation of treatment response with the amount of orbitofrontal gray matter. Thus, we demonstrate adaptive gray matter changes within the pain modulatory system in patients with MOH who responded to detoxification, probably reflecting neuronal plasticity. Decreased gray matter in the orbitofrontal cortex at baseline may be predictive of poor response to treatment.

Acute confusional migraine: our knowledge to date

Acute confusional migraine (ACM) is a rare migraine variant, affecting children and adolescents, as well as adults. Between 0.45 and 7.8% of children with migraine present with ACM, but the disorder may well be underdiagnosed. ACM is an exclusion diagnosis and some dangerous causes of confusion (e.g., epilepsy, ischemia, hemorrhagia, neoplasm, intoxication and encephalitis) should be ruled out. The confusional state often manifests with a wide diversity of cortical dysfunctions, such as speech difficulties, increased alertness, agitation and amnesia. Exact history taking, clinical examination, and laboratory, radiological and electroencephalographical findings lead the practitioner towards the diagnosis. Approximately half of the cases may be triggered by mild head trauma. Transient global amnesia is an important differential diagnosis, possibly caused by similar pathophysiological mechanisms. The exact pathomechanism remains unclear, with the common hypothesis comprising of the confusional state as a complex aura phenomenon, in which the cortical spreading depression wave reaches not only the occipital, but also the temporal, parietal and frontal cortex, as well as the brainstem and the hippocampi, leading to transient hypoperfusion and dysfunction of these brain areas.

Efficacy and safety of 121 injections of the greater occipital nerve in episodic and chronic cluster headache

Introduction: Infiltration of the greater occipital nerve (GON) with local anaesthetics and corticosteroids is a treatment option for cluster headache. Methods: We retrospectively analysed the efficacy and safety of 121 GON injections in 60 patients with episodic or chronic cluster headache over a period of 4 years. Results: Almost 80% of the infiltrations were at least partially effective (reduction of attack frequency, duration or severity) and 45% resulted in a complete response (no further attacks). The effect was maintained for 3.5 weeks on average in chronic cluster headache. In episodic cluster headache, the effect lasted for most of the bout. In 18 infiltrations, transient side effects were reported, such as local pain, steroid effects (facial oedema, sleeping disorders, acne), bradycardia or syncope. Conclusion: Our data show that GON infiltration is a valuable and safe option in the clinical setting to treat patients suffering from cluster headache, especially for the episodic form of the disorder.

Headache frequency and intensity in female migraineurs using desogestrel-only contraception: a retrospective pilot diary study.

Background Migraine seems to be substantially related to hormonal changes. However, migraine, but also the use of combined oral contraceptives (COC), is associated with an increased risk for vascular events. Therefore progestagen-only contraception is an important alternative to combined preparations. Clinical observations and one pilot study demonstrate that the use of desogestrel 75 µg may have a positive impact on migraine. Aim The aim of this retrospective analysis of prospectively collected headache diaries was to study the effect of desogestrel 75 µg on headache frequency, intensity and use of acute medication in premenopausal women with migraine in a clinical setting. Methods Patients’ charts were included from women who wanted to use desogestrel 75 µg as a contraceptive and had kept headache diaries over six months (three months pretreatment and three months during treatment). Out of 58 women, 38 women had completed headache diaries for this period. Incomplete diaries (n = 12), side effects (n = 5) and loss to follow-up (n = 3) were the reasons for the exclusion of 20 women. The three months (total of 90 days) before and after initiation of the progestin were compared. Results Days with migraine (5.2 vs. 3.7), days with all kind of headache (8.3 vs. 6.5) and days with use of any headache medication (5.7 vs. 3.5) were significantly reduced at follow-up after three months. In addition there was a reduction in headache intensity (p < 0.0001). The reduction in number of days with use of triptans was not significant (p < 0.14). Conclusion In the 38/58 migraineurs with complete diaries there was a statistically significant decrease in migraine days, headache intensity and medication use. Tension-type headache days decreased but were not significant. Our preliminary data are promising, but should be interpreted cautiously because they were obtained in a small population of women visiting a specialty hormone and migraine clinic. Randomised controlled trials need to be conducted to substantiate our results.

Physiological Parameters as Biomarkers of Migraine

We review physical signs and measurements from neurophysiological research, which may be considered biomarkers of migraine. Most studies show that information processing is abnormal in migraineurs. Studies of trigeminal nociception are in line with a central sensitization during the attack. The best documented abnormality is an interictal lack of habituation in migraineurs, with a normalization during the headache state, which has been shown using evoked and event‐related potentials. Together with a diminished energy reserve found in MR‐spectroscopy studies, these results suggest a possible role of increased energy consumption in attack generation. Importantly, to date, no neurophysiological marker has a high enough sensitivity and specificity to point out the single migraine patient. Therefore, these biomarkers are to be understood as tools for research and are not to be used for diagnostic purposes.

Desogestrel-only contraception may reduce headache frequency and improve quality of life in women suffering from migraine

Abstract Objective To analyse the effects of a three-month course of progestogen-only contraception with desogestrel 75 μg on disability, headache frequency and headache intensity in migraineurs. Materials and methods Migraine disability headache questionnaires (MIDAS) were collected from 37 migraineurs during counselling, and at the end of three months treatment with desogestrel. Another ten women initiated but did not complete treatment. They are included in the overall evaluations of the effect of the regimen on migraine status. Results Desogestrel was associated with significant reductions in headache days and intensity (p < 0.001; p < 0.006), and a significant improvement in quality of life. Days missed at work and days missing leisure activities diminished (p < 0.001; p < 0.001). The MIDAS migraine disability score improved significantly (from 27.4 to 11.1 points) (p < 0.001). While 25 of the 37 women (68%) experienced a decrease of at least one grade, this level of benefit cannot be extrapolated to all initiators. When dropouts are considered, MIDAS grades decrease in 53% (25/47) of the cases. Conclusion The majority of migraineurs experienced a clinically significant reduction in headache frequency and improvement of quality of life with use of desogestrel. Prospective randomised controlled trials are needed to substantiate our results.

Prevalence of medication overuse headache in an interdisciplinary pain clinic

BackgroundMedication overuse headache (MOH) has been recognized as an important problem in headache patients although the pathophysiological mechanisms remain unclear. The diagnosis of MOH is based on clinical characteristics defined by the International Headache Society. The aim was the evaluation of the diagnostic criteria of MOH in a mixed population of chronic pain patients to gain information about the prevalence and possible associations with MOH.MethodsData of all patients referred to the interdisciplinary pain clinic at the University Hospital of Zurich between September 2005 and December 2007 were retrospectively analyzed. Demographic data (age, sex, history of migration), as well as data about duration of pain disease, category of pain disease (neurological, psychiatric, rheumatologic, other), use of medication, history of trauma, and comorbidity of depression and anxiety have been collected.ResultsTotally 178 of 187 consecutive chronic pain patients were included in the study. A total of 138 patients (78%) used analgesics on 15 or more days per month. Chronic headache was more prevalent among patients with analgesic overuse (39.8%) than without analgesic overuse (18%). The prevalence of MOH was 29%. The odds ratio (OR) for a patient with medication overuse to have chronic headache was 13.1 if he had a history of primary headache, compared to a patient without a primary headache syndrome. Furthermore, history of headache (OR 2.5, CI [1.13;5.44]), history of migration (OR 2.9, CI [1.31;6.32]) and comorbid depression (OR 3.5, CI [1.46;8.52]) were associated with overuse of acute medication, in general.ConclusionsPrimary headaches have a high risk for chronification in patients overusing analgesics for other pain disorders. Whereas history of headache, history of migration and comorbidity of depression are independentely associated with analgesic overuse in this group of patients.

Positive effects of the progestin desogestrel 75 μg on migraine frequency and use of acute medication are sustained over a treatment period of 180 days

BackgroundPremenopausal migraines frequently are associated with fluctuations of estrogen levels. Both, migraine and combined hormonal contraceptives (CHC) increase the risk of vascular events. Therefore progestagen-only contraceptives (POC) are a safer alternative. A previous short-term study demonstrated a positive impact of the oral POC desogestrel on migraine frequency. To study the effect of the POC desogestrel 75 μg on migraine frequency, intensity, use of acute medication and quality of life in a clinical setting over the period of 180 days.MethodsPatients’ charts were screened for women with migraine, who had decided to use desogestrel for contraception. Charts were included, if routinely conducted headache diaries were complete for 90 days before treatment (baseline) and over a treatment period of 180 days. We also report about starters who stopped treatment early, because of adverse events. Baseline data (day 1–90 before treatment) were compared with first and second treatment period (treatment days 1–90 and days 91–180). Quality of life was evaluated using MIDAS questionnaires.ResultsDays with migraine (5.8 vs 3.6), with any kind of headache (9.4 vs 6.6), headache intensity (15.7 vs 10.7), days with severe headache (5.4 vs 2.4) and use of triptans (12.3 vs7.8) were significantly reduced after 180 days. MIDAS score and grade improved significantly.ConclusionContraception with desogestrel 75 μg resulted in a significantly improved quality of life and a reduction of migraine days over the observation period of 180 days. A clinically meaningful 30% reduction in pain was observed in 25/42 (60%) participants. For counselling reasons it is of importance, that the major reduction in migraine frequency occured during the initial 90 days, however further improvement occurs with longer duration of use. Prospective studies are needed to confirm these results.

Feeding dystonia in McLeod Syndrome

The X‐linked McLeod syndrome belongs to the group of neuroacanthocytosis syndromes and has a Huntington‐disease–like phenotype with a choreatic movement disorder, cognitive alterations, and psychiatric symptoms. Another neuroacanthocytosis syndrome, the autosomal recessive chorea‐acanthocytosis, has a similar presentation, but distinct clinical features, believed to be characteristic, such as tongue protrusion dystonia, feeding dystonia, and rubber‐man–like appearance.