EEG microstate periodicity explained by rotating phase patterns of resting-state alpha oscillations.

Spatio-temporal patterns in electroencephalography (EEG) can be described by microstate analysis, a discrete approximation of the continuous electric field patterns produced by the cerebral cortex. Resting-state EEG microstates are largely determined by alpha frequencies (8-12 Hz) and we recently demonstrated that microstates occur periodically with twice the alpha frequency. To understand the origin of microstate periodicity, we analyzed the analytic amplitude and the analytic phase of resting-state alpha oscillations independently. In continuous EEG data we found rotating phase patterns organized around a small number of phase singularities which varied in number and location. The spatial rotation of phase patterns occurred with the underlying alpha frequency. Phase rotors coincided with periodic microstate motifs involving the four canonical microstate maps. The analytic amplitude showed no oscillatory behaviour and was almost static across time intervals of 1-2 alpha cycles, resulting in the global pattern of a standing wave. In n=23 healthy adults, time-lagged mutual information analysis of microstate sequences derived from amplitude and phase signals of awake eyes-closed EEG records showed that only the phase component contributed to the periodicity of microstate sequences. Phase sequences showed mutual information peaks at multiples of 50 ms and the group average had a main peak at 100 ms (10 Hz), whereas amplitude sequences had a slow and monotonous information decay. This result was confirmed by an independent approach combining temporal principal component analysis (tPCA) and autocorrelation analysis. We reproduced our observations in a generic model of EEG oscillations composed of coupled non-linear oscillators (Stuart-Landau model). Phase-amplitude dynamics similar to experimental EEG occurred when the oscillators underwent a supercritical Hopf bifurcation, a common feature of many computational models of the alpha rhythm. These findings explain our previous description of periodic microstate recurrence and its relation to the time scale of alpha oscillations. Moreover, our results corroborate the predictions of computational models and connect experimentally observed EEG patterns to properties of critical oscillator networks.

[S2k guidelines: status epilepticus in adulthood : Guidelines of the German Society for Neurology]. / S2k-Leitlinie: Status Epilepticus im Erwachsenenalter : Leitlinie der Deutschen Gesellschaft für Neurologie.

This S2k guideline on diagnosis and treatment of status epilepticus (SE) in adults is based on the last published version from 2021. New definitions and evidence were included in the guideline and the clinical pathway. A seizures lasting longer than 5 minutes (or ≥ 2 seizures over more than 5 mins without intermittend recovery to the preictal neurological state. Initial diagnosis should include a cCT or, if possible, an MRI. The EEG is highly relevant for diagnosis and treatment-monitoring of non-convulsive SE and for the exclusion or diagnosis of psychogenic non-epileptic seizures. As the increasing evidence supports the relevance of inflammatory comorbidities (e.g. pneumonia) related clinical chemistry should be obtained and repeated over the course of a SE treatment, and antibiotic therapy initiated if indicated.Treatment is applied on four levels: 1. Initial SE: An adequate dose of benzodiazepine is given i.v., i.m., or i.n.; 2. Benzodiazepine-refractory SE: I.v. drugs of 1st choice are levetiracetam or valproate; 3. Refractory SE (RSE) or 4. Super-refractory SE (SRSE): I.v. propofol or midazolam alone or in combination or thiopental in anaesthetic doses are given. In focal non-convulsive RSE the induction of a therapeutic coma depends on the circumstances and is not mandatory. In SRSE the ketogenic diet should be given. I.v. ketamine or inhalative isoflorane can be considered. In selected cased electroconvulsive therapy or, if a resectable epileptogenic zone can be defined epilepsy surgery can be applied. I.v. allopregnanolone or systemic hypothermia should not be used.

Intravenous lacosamide for treatment of absence status epilepticus in genetic generalized epilepsy: A case report and review of literature.

BACKGROUND: Nearly 10 years after its introduction into the market, the significance of lacosamide in genetic generalized epilepsies is still unclear. Its new mode of action may qualify lacosamide as a therapeutic agent in this entity, but only a limited number of cases have been published so far. AIM: To describe the efficacy of lacosamide as treatment in a patient with the absence status epilepticus. METHOD: We report on a 28-year-old woman with genetic generalized epilepsy who suffered recurrent absence status epilepticus during video-EEG-monitoring. After treatment failure of first- and second-line medication, lacosamide was administered. The outcome in this patient was evaluated, and a systematic literature review was performed for the use of lacosamide in the absence status epilepticus. RESULTS: After application of 400 mg lacosamide intravenously, the absence status epilepticus terminated within 30 minutes. No further seizures or epileptiform discharges reoccurred until the end of video-EEG-Monitoring 3 days later. CONCLUSIONS: The role of lacosamide as a therapeutic option in patients with the absence status epilepticus is unclear. Only two cases have been reported so far with conflicting results. Further randomized controlled studies are required to validate the relevance of lacosamide as treatment for status epilepticus in genetic generalized and the absence epilepsy.

Long-term adjunctive lacosamide treatment in patients with partial-onset seizures.

OBJECTIVE: To evaluate long-term (up to 5.5 years) safety, seizure reduction, and maintenance of efficacy of the antiepileptic drug (AED) lacosamide as adjunctive treatment in an open-label extension trial (SP774; ClinicalTrials.gov: NCT00515619). METHODS: Three hundred and seventy-six adults with partial-onset seizures taking 1-3 AEDs enrolled following completion of a double-blind trial of adjunctive lacosamide. During open-label treatment, dosage of lacosamide (100-800 mg/day) and/or concomitant AEDs could be adjusted to optimize tolerability and seizure control. RESULTS: Kaplan-Meier estimates of patient retention were 74.5% at 12 months, 52.9% at 36 months, and 40.6% at 60 months; median open-label treatment duration was 1183 days (~3.2 years). The most frequently reported treatment-emergent adverse events were dizziness (24.2%), headache (14.4%), diplopia (13.8%), and nasopharyngitis (13.8%); 9.0% of patients discontinued due to adverse events, most commonly dizziness (1.3%). Median percent reduction in 28-day seizure frequency from baseline of the double-blind trial was 49.9% overall, 55.4% for 1-year completers, and 62.3% for 3-year completers. Overall, 50.0% of patients were considered ≥50% responders (achieved ≥50% reduction in 28-day seizure frequency); 55.9% of 1-year completers and 63.0% of 3-year completers were ≥50% responders. CONCLUSION: In eligible patients who entered the open-label extension trial, lacosamide was generally well tolerated. For most patients within each yearly completer cohort, seizure reduction was maintained over time.

Adjunctive retigabine in refractory focal epilepsy: Postmarketing experience at four tertiary epilepsy care centers in Germany.

PURPOSE: Retigabine (RTG, ezogabine) is the first potassium channel-opening anticonvulsant drug approved for adjunctive treatment of focal epilepsies. We report on the postmarketing clinical efficacy, adverse events, and retention rates of RTG in adult patients with refractory focal epilepsy. METHODS: Clinical features before and during RTG treatment were retrospectively collected from patients treated at four German epilepsy centers in 2011 and 2012. RESULTS: A total of 195 patients were included. Daily RTG doses ranged from 100 to 1500 mg. Retigabine reduced seizure frequency or severity for 24.6% and led to seizure-freedom in 2.1% of the patients but had no apparent effect in 43.1% of the patients. Seizure aggravation occurred in 14.9%. The one-, two-, and three-year retention rates amounted to 32.6%, 7.2%, and 5.7%, respectively. Adverse events were reported by 76% of the patients and were mostly CNS-related. Blue discolorations were noted in three long-term responders. Three possible SUDEP cases occurred during the observation period, equalling an incidence rate of about 20 per 1000 patient years. CONCLUSIONS: Our results are similar to other pivotal trials with respect to the long-term, open-label extensions and recent postmarketing studies. Despite the limitations of the retrospective design, our observational study suggests that RTG leads to good seizure control in a small number of patients with treatment-refractory seizures. However, because of the rather high percentage of patients who experienced significant adverse events, we consider RTG as a drug of reserve.

[Brivaracetam for add-on treatment in focal epilepsy]. / Brivaracetam zur Zusatztherapie bei fokalen Epilepsien.

Brivaracetam is the latest antiepileptic drug to be approved for adjunctive therapy in focal epilepsy and has a high affinity as a SV2A ligand. The aim of this review article is to summarize the data from the pivotal studies in which more than 2000 patients received brivaracetam. A significant median reduction in seizures from 30.5 % to 53.1 % for 50 mg/day, from 32.5 % to 37.2 % for 100 mg/day and 35.6 % for 200 mg/day could be demonstrated. Overall brivaracetam appears to be well-tolerated, with fatigue, dizziness and somnolence being the main adverse side effects. An immediate change from levetiracetam to brivaracetam at a conversion ratio of 10:1 to 15:1 seems feasible and could alleviate behavioral side effects related to treatment with levetiracetam. A swift permeability into brain tissue and a faster onset of action compared to levetiracetam suggest that brivaracetam could be useful in emergency situations.

Stiripentol for the treatment of super-refractory status epilepticus.

BACKGROUND: To determine whether stiripentol (STP) might be a treatment option in super-refractory status epilepticus (SRSE). METHODS: Medical records of patients treated due to a status epilepticus in Marburg between January 2013 and June 2014 were reviewed for administration of STP. Primary outcome measures were resolution of SE after initiation of STP. RESULTS: Five adult patients were started with STP due to SRSE. The median age was 78 years (interquartile range [IQR] 11 years), and four patients were female. The median duration of SRSE before initiation of STP was 39 days (IQR 16 days), and the median number of anticonvulsants used before was 6 (IQR 1). SRSE ceased in three patients within 2-4 days after the start of STP. In two patients, SRSE continued after administration of STP and further escalation of anticonvulsant regimen. Both were switched eventually to supportive care only. None serious side effects were observed while on STP. CONCLUSIONS: Based on our presented cases and previous experimental animal data, STP may prove useful in treating super-refractory SE. Prospective trials are warranted to examine the efficacy of the STP in adults with refractory SE and to examine whether earlier treatment leads to better control of SE.

Epilepsy in the elderly: restrictions, fears, and quality of life.

OBJECTIVES: Due to demographic change and high incidence of epilepsy in elderly, the number of elderly with epilepsies is increasing. However, only few studies investigated the impact of epilepsy on quality of life (QoL). We investigated how epilepsy affects different aspects of QoL dependent on the age of the patients and the age of onset of epilepsy. MATERIALS AND METHODS: In a multicenter, cross-sectional study, three patient groups were recruited from five centers: Group A1: 45 elderly (≥65 years.) with late onset of epilepsy (≥65 years), group A2: 51 elderly (≥65 years.) with early-onset, long-lasting epilepsy (≤50 years), group B: 41 young adults (≤50 years) with epilepsy. Statistical analysis of differences between groups was performed using generalized linear models. RESULTS: Elderly with late-onset epilepsy (group A1) had a significantly lower seizure frequency, were treated with less anti-epileptic drugs (AEDs), and reported a better tolerability of AED treatment, but had more comorbidities compared with groups A2 and B. After adjusting for seizure frequency, tolerability of AEDs and comorbidity, young adults (group B) reported the highest overall QoL, whereas patients of group A1 and A2 did not differ significantly. Epilepsy-related fears, especially fears of stigmatization, were significantly higher in elderly with long-lasting epilepsy compared with groups A1 and B. CONCLUSION: Seizure-related variables, tolerability of AEDs and comorbidity have a stronger impact on QoL and on restrictions due to epilepsy than age, age at onset of epilepsy or duration of epilepsy. However, some results indicate group-specific patterns of impairment and epilepsy-related fears.

Epilepsy in the elderly: comparing clinical characteristics with younger patients.

The prevalence and incidence of epilepsies in elderly is high. Due to demographic development, the portion of elderly patients with epilepsy will continue to rise over the next decades. In this study, we aimed to investigate seizure semiology, etiology, comorbidity, and therapy in elderly patients dependent on onset of epilepsy and in comparison with younger patients. In a prospective multicentre study, 202 epilepsy patients were included in a consecutive manner and subdivided into three groups (group A1: >65 years, onset of epilepsy after the age of 65 years; group A2: >65 years with early onset epilepsy, seizure onset before the age of 50 years; and group B: <50 years with epilepsy). Clinical data with respect to epilepsy, seizures, comorbidity, etiology, and anti-epileptic drug (AED) therapy were assessed using a questionnaire developed especially for these patient groups and filled out by the physicians. The clinical profile with regard to etiology, postictal conditions, and comorbidities clearly depends on the age of the patients and age of onset of epilepsy. Patients with an epilepsy onset after 65 years need lower doses of AEDs, gain better seizure control and have more concomitant diseases than younger patients or elderly epilepsy patients with early-onset epilepsy.

[New aspects in the field of epilepsy]. / Neues auf dem Gebiet der Epilepsien.

Regarding epilepsy several new developments can be reported. The International League Against Epilepsy (ILAE) has suggested a new definition of epilepsy, for the first time including a definition of epilepsy resolution. Progress in the diagnosis relates to new genetic findings, improvements in magnetic resonance imaging (MRI) and the increasing use of stereo electroencephalograms (sEEG). Regarding treatment there are new clinically relevant data on the pathophysiology and prevention of sudden unexpected death in epilepsy (SUDEP). Zonisamide has been approved by the European Medicines Agency (EMA) for monotherapy in adults with focal seizures and combination therapy in children aged ≥ 6 years. Retigabin and perampanel have been approved but are currently taken off the market in Germany (only) because the Gemeinsamer Bundesausschuss (GBA, Joint Federal Committee) did not find any additional therapeutic value as compared to lamotrigine due to a lack of data. A decision regarding a new application for perampanel is pending. Regarding surgical treatment novel ablation techniques (e.g. stereotactic radiofrequency and laser ablation as well as focussed ultrasound ablation) and brain stimulation paradigms are under investigation. Experimental studies, generously supported by the European Union (EU) and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) are focusing on (opto-)genetic (e.g. using lentoviral transfection), epigenetic (e.g. micro-RNA-related) approaches and on the investigation of neuronal micronetworks.

[Quality guidelines for presurgical epilepsy diagnosis and operative epilepsy therapy: 1st revised version]. / Qualitätsleitlinien für prächirurgische Epilepsiediagnostik und operative Epilepsietherapie : 1. Neufassung.

In patients with pharmacorefractory epilepsy, preoperative epilepsy evaluation and subsequent epilepsy surgery lead to a significant improvement of seizure control, proportion of seizure-free patients, quality of life and social participation. The aims of preoperative epilepsy evaluation are to define the chance of complete seizure freedom and the likelihood of inducing new neurological deficits in a given patient. As epilepsy surgery is an elective procedure quality standards are particularly high. As detailed in the first edition of these practice guidelines, quality control relates to seven different domains: (1) establishing centres with a sufficient number of sufficiently and specifically trained personnel, (2) minimum technical standards and equipment, (3) continuing medical education of employees, (4) surveillance by trained personnel during the video electroencephalography (EEG) monitoring (VEM), (5) systematic acquisition of clinical and outcome data, (6) the minimum number of preoperative evaluations and epilepsy surgery procedures and (7) cooperation of epilepsy centres. In the first edition of these practice guidelines published in 2000 it was defined which standards were desirable and that their implementation should be aimed for. These standards related especially to the certification required for different groups of medical doctors involved and to the minimum numbers of procedures required. In the subsequent decade quite a number of colleagues have been certified by the trinational Working Group (Arbeitsgemeinschaft, AG) for Presurgical Epilepsy Diagnosis and Operative Epilepsy Treatment (http://www.ag-epilepsiechirurgie.de) and therefore, on 8 May 2013 the executive board of the AG decided to now make these standards obligatory.

[Transcranial magnetic stimulation and motor cortex stimulation in neuropathic pain]. / Transkranielle Magnetstimulation und Motorkortexstimulation bei neuropathischen Schmerzen.

Non-invasive and invasive cortical stimulation allows the modulation of therapy-refractory neuropathic pain. High-frequency repetitive transcranial magnetic stimulation (rTMS) of the contralateral motor cortex yields therapeutic effects at short-term and predicts the benefits of epidural motor cortex stimulation (MCS). The present article summarizes the findings on application, mechanisms and therapeutic effects of cortical stimulation in neuropathic pain.

[Non-convulsive status epilepticus: temporary fad or reality in need of treatment?]. / Nonkonvulsiver Status epilepticus : Modeerscheinung oder behandlungspflichtige Realität?

The term non-convulsive status epilepticus (NCSE) refers to a heterogeneous group of diseases with different etiology, prognosis and treatment. The different forms of NCSE comprise about 25-50% of all status epilepticus cases. The most frequent form encountered in clinical practice is complex-partial SE but the rarer conditions of absence status, aura status and subtle SE are also included under this category. A diagnosis of NCSE should be considered in all patients with otherwise unexplained changes in consciousness or behavior and this diagnosis demands rapid further diagnostic work up including clinical examination, a detailed clinical history from the patient or an accompanying person, cranial computed tomography (CCT) and an electroencephalogram (EEG). If signs of an infectious or inflammatory disorder are present, a spinal tap is indicated. The EEG is of high relevance although interpretation can be challenging in NCSE.Absence status is usually treated by benzodiazepines and if necessary a broad spectrum anticonvulsive drug (ACD) such as valproic acid (VPA) can be added. The treatment of complex-partial SE follows the same scheme as that of generalized tonic-clonic SE and an initial benzodiazepine (i.v. lorazepam or intramuscular midazolam) followed by a bolus of one of the ACDs available as i.v. solution (e.g. VPA, phenytoin, phenobarbitol or levetiracetam). The third treatment step is general anesthesia if NCSE fails to be controlled. The aggressiveness of the applied therapy depends on the severity of the NCSE and the general condition of the patient. The prognosis is determined by the subtype of NCSE and the underlying etiology.

Men and women are different: diffusion tensor imaging reveals sexual dimorphism in the microstructure of the thalamus, corpus callosum and cingulum.

INTRODUCTION: Numerous magnetic resonance imaging (MRI) studies have addressed the question of morphological differences of the brain of men and women, reporting conflicting results regarding brain size and the ratio of gray and white matter. In the present study, we used diffusion tensor imaging (DTI) to delineate sex differences of brain white matter. METHODS: We investigated brain microstructure in 25 male and 25 female healthy subjects using a 3T MRI scanner. Whole-head DTI scans were analyzed without a-priori hypothesis using Tract-Based Spatial Statistics (TBSS) calculating maps of fractional anisotropy (FA), radial diffusivity (RD, a potential marker of glial alteration and changes in myelination) and axial diffusivity (AD, a potential marker of axonal changes). RESULTS: DTI revealed regional microstructural differences between the brains of male and female subjects. Those were prominent in the thalamus, corpus callosum and cingulum. Men showed significantly (p<0.0001) higher values of fractional anisotropy and lower radial diffusivity in these areas, suggesting that the observed differences are mainly due to differences in myelination. DISCUSSION: As a novel finding we showed widespread differences in thalamic microstructure that have not been described previously. Additionally, the present study confirmed earlier DTI studies focusing on sexual dimorphism in the corpus callosum and cingulum. All changes appear to be based on differences in myelination. The sex differences in thalamic microstructure call for further studies on the underlying cause and the behavioral correlates of this sexual dimorphism. Future DTI group studies may carefully control for gender to avoid confounding.

Intravenous lacosamide for treatment of status epilepticus.

OBJECTIVES: Treatment of established status epilepticus (SE) requires immediate intravenous anticonvulsant therapy. Currently used first-line drugs may cause potentially hazardous side effects. We aimed to assess the efficacy and safety of intravenous lacosamide (LCM) in SE after failure of standard treatment. METHODS: We retrospectively analyzed 39 patients (21 women, 18 men, median age 62 years) from the hospital databases of five neurological departments in Germany, Austria and Switzerland between September 2008 and January 2010 who were admitted in SE and received at least one dose of intravenous LCM. RESULTS: Types of SE were generalized convulsive (n = 6), complex partial (n = 17) and simple partial (n = 16). LCM was administered after failure of benzodiazepins or other standard drugs in all but one case. Median bolus dose of LCM was 400 mg (range 200-400 mg), which was administered at 40-80 mg/min in those patients where infusion rate was documented. SE stopped after LCM in 17 patients, while 22 patients needed further anticonvulsant treatment. The success rate in patients receiving LCM as first or second drug was 3/5, as third drug 11/19, and as fourth or later drug 3/15. In five subjects, SE could not be terminated at all. No serious adverse events attributed to LCM were documented. CONCLUSIONS: Intravenous LCM may be an alternative treatment for established SE after failure of standard therapy, or when standard agents are considered unsuitable.

Intraoperative ultrasound in malformations of cortical development.

PURPOSE: Malformations of cortical development (MCD) are a common cause of medically refractory focal epilepsy. However, the intraoperative definition of MCD can be challenging. In this study we assess the feasibility of intraoperative ultrasound (IOUS) for the intraoperative localization of MCD. MATERIALS AND METHODS: Five epilepsy patients with at least one suspected lesion of MCD were operated with the aid of IOUS. IOUS was compared to preoperative MRI and histopathology. RESULTS: In three cases of focal cortical dysplasia (FCD) type IIB and one case of periventricular heterotopia, the lesions could be delineated well on IOUS and the configuration of the lesion corresponded to the appearance on MRI. However, only one of two FCD type I lesions could be detected on IOUS. CONCLUSION: IOUS can be helpful in defining FCD IIB as well as periventricular heterotopia intraoperatively, but this seems to be more difficult in FCD type I.

Heterotopia in Individuals with 22q11.2 Deletion Syndrome.

BACKGROUND AND PURPOSE: MR imaging studies and neuropathologic findings in individuals with 22q11.2 deletion syndrome show anomalous early brain development. We aimed to retrospectively evaluate cerebral abnormalities, focusing on gray matter heterotopia, and to correlate these with subjects' neuropsychiatric impairments. MATERIALS AND METHODS: Three raters assessed gray matter heterotopia and other morphologic brain abnormalities on 3D T1WI and T2*WI in 75 individuals with 22q11.2 deletion syndrome (27 females, 15.5 [SD, 7.4] years of age) and 53 controls (24 females, 12.6 [SD, 4.7] years of age). We examined the association among the groups' most frequent morphologic findings, general cognitive performance, and comorbid neuropsychiatric conditions. RESULTS: Heterotopia in the white matter were the most frequent finding in individuals with 22q11.2 deletion syndrome (n = 29; controls, n = 0; between-group difference, P < .001), followed by cavum septi pellucidi and/or vergae (n = 20; controls, n = 0; P < .001), periventricular cysts (n = 10; controls, n = 0; P = .007), periventricular nodular heterotopia (n = 10; controls, n = 0; P = .007), and polymicrogyria (n = 3; controls, n = 0; P = .3). However, individuals with these morphologic brain abnormalities did not differ significantly from those without them in terms of general cognitive functioning and psychiatric comorbidities. CONCLUSIONS: Taken together, our findings, periventricular nodular heterotopia or heterotopia in the white matter (possibly related to interrupted Arc cells migration), persistent cavum septi pellucidi and/or vergae, and formation of periventricular cysts, give clues to the brain development disorder induced by the 22q11.2 deletion syndrome. There was no evidence that these morphologic findings were associated with differences in psychiatric or cognitive presentation of the 22q11.2 deletion syndrome.

Stiripentol in the treatment of adults with focal epilepsy- a retrospective analysis.

OBJECTIVES: The aim of the present study was to evaluate the safety and efficacy of the add-on treatment of stiripentol (STP) in adult patients with severely pharmacoresistant focal or multifocal epilepsy. METHODS: Data on adult patients treated with STP from March 2007 to July 2020 and with at least one clinical follow-up (FU) were retrospectively reviewed. Data on tolerability, efficacy and concomitant medication were evaluated at baseline, 6 months (5.5 ± 1.6 months (mean ± SD)) and 12 months (13.1 ± 3.9 months (mean ± SD)). RESULTS: Data of 22 patients (54.5% male, mean age 34.4 ± 17.79 years (mean ± SD), including mean duration of epilepsy 17.6 ± 25.5 years (mean ± SD), median seizure frequency 30 ± 20 (median ± MAD) per month, and 63.6% being severely intellectually disabled, with 3 to 18 previous anti-seizure-drugs (ASD), were collected. After 6 months, 72.7% of the patients were still taking STP, and 31% of the patients were responders, including 13% who were seizure-free. The 12-month retention rate was 54.4 %, the response rate was 36.4% and 13.6% of patients were seizure-free at the 12-month FU. Reasons for discontinuation were increased seizure frequency, hyperammonaemia and encephalopathy. CONCLUSION: STP seems to be a useful option in the treatment of patients with severely pharmacoresistant epilepsy. Prospective trials are necessary to examine the efficacy of STP in adult patients with pharmacoresistant focal epilepsy.

Low-frequency rTMS of the vertex in the prophylactic treatment of migraine.

High-frequency repetitive transcranial magnetic stimulation (rTMS) increases and low-frequency rTMS decreases neural excitability. Clinically, rTMS shows beneficial effects in the treatment of neurological and psychiatric disorders. Furthermore, chronic and neuropathic pain has been shown to respond to rTMS treatment. A small pilot study revealed prophylactic effects of high-frequency rTMS in migraine. As there is evidence of neuronal hyperexcitability in migraine, we conducted a placebo-controlled, blinded study to evaluate the therapeutic effects of low-frequency rTMS in migraine. The primary end-point was defined as a reduction of migraine attacks compared with placebo, secondary outcomes were a reduction in the total number of days with headache, hours with headache, pain intensity and a decrease of analgesic intake for migraine. Twenty-seven migraineurs completed the study and were treated with rTMS on five consecutive days. For the verum group, two trains of 500 pulses with a frequency of 1 Hz were applied over vertex with a round coil. For the treatment of the placebo group, a figure-of-eight sham coil was used. A significant decrease of migraine attacks could be observed in the verum group. However, when comparing these effects with placebo, no significance was evident. The same was true concerning secondary outcome measures with regard to days with migraine and total hours with migraine. No effects were evident for pain intensity and use of analgesics. The rTMS treatment was tolerated well. rTMS stimulation over vertex with 1 Hz was not effective in migraine prophylaxis when compared with placebo. The positive effects regarding migraine attacks, days and total hours with migraine in the verum group are encouraging and indicate that further research on this topic is warranted.