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.

[Smarter Medicine in Headache Care - presentation and discussion of 5 recommendations]. / Smarter Medicine in Diagnose und Behandlung von Kopfschmerzen.

Smarter Medicine in Headache Care - presentation and discussion of 5 recommendations Abstract. An unequivocal headache diagnosis cannot always be made. The lack of diagnostic tests able to prove primary headaches often prompts physicians to perform unnecessary examinations to reduce their uncertainty. When setting out the therapeutic strategy, again, insecurity often leads to mendable choices. In this Delphi study, members of the therapy commission of the Swiss Headache Society collected, rated, and re-rated doubtful and questionable procedures. Five recommendations that resulted from this survey are presented and reviewed in this article. The recommendations are: (A) no repeated cerebral imaging in headaches with unchanged phenotype; (B) no computed tomography in the work-up of non-acute headaches; (C) no tooth extraction to treat persistent idiopathic facial pain, (D) no migraine surgery; (E) no removal of amalgam fillings to treat headache disorders.

[New anticonvulsants in everyday clinical use]. / Neue Antikonvulsiva im klinischen Alltag.

New anticonvulsants in everyday clinical use Abstract. In summary, the armamentarium of the clinically active epileptologist is constantly expanding. The newer substances often show a better tolerability and a lower interaction potential than the older substances, but they are not more effective. The selection of the anticonvulsant depends on the individual situation and takes into account the type of epilepsy, age, comorbidities and, in the case of women, any desire to have children. Because epilepsies are often still refractory to therapy, new substances are urgently needed and several promising preparations are currently under development. Epilepsy surgery is also making great progress, so it is recommended that, after the unsuccessful use of two adequate anticonvulsants, this often very successful option be considered, which ideally leads to a cure from epilepsy, and that patients be referred to an appropriate centre.

De novo status epilepticus with isolated aphasia.

BACKGROUND: Sudden onset of aphasia is usually due to stroke. Rapid diagnostic workup is necessary if reperfusion therapy is considered. Ictal aphasia is a rare condition but has to be excluded. Perfusion imaging may differentiate acute ischemia from other causes. In dubious cases, EEG is required but is time-consuming and laborious. We report a case where we considered de novo status epilepticus as a cause of aphasia without any lesion even at follow-up. A 62-year-old right-handed woman presented to the emergency department after nurses found her aphasic. She had undergone operative treatment of varicosis 3 days earlier. Apart from hypertension and obesity, no cardiovascular risk factors and no intake of medication other than paracetamol were reported. Neurological examination revealed global aphasia and right pronation in the upper extremity position test. Computed tomography with angiography and perfusion showed no abnormalities. Electroencephalogram performed after the CT scan showed left-sided slowing with high-voltage rhythmic 2/s delta waves but no clear ictal pattern. Intravenous lorazepam did improve EEG slightly, while aphasia did not change. Lumbar puncture was performed which likely excluded encephalitis. Magnetic resonance imaging showed cortical pathological diffusion imaging (restriction) and cortical hyperperfusion in the left parietal region. Intravenous anticonvulsant therapy under continuous EEG resolved neurological symptoms. The patient was kept on anticonvulsant therapy. Magnetic resonance imaging after 6 months showed no abnormalities along with no clinical abnormalities. CONCLUSIONS: Magnetic resonance imaging findings were only subtle, and EEG was without clear ictal pattern, so the diagnosis of aphasic status remains with some uncertainty. However, status epilepticus can mimic stroke symptoms and has to be considered in patients with aphasia even when no previous stroke or structural lesions are detectable and EEG shows no epileptic discharges. Epileptic origin is favored when CT or MR imaging reveal no hypoperfusion. In this case, MRI was superior to CT in detecting hyperperfusion. This article is part of a Special Issue entitled "Status Epilepticus".

Cortical abnormalities and their cognitive correlates in patients with temporal lobe epilepsy and interictal psychosis.

PURPOSE: To determine whether cortical abnormalities are more severe and widespread in patients with temporal lobe epilepsy (TLE) and interictal psychosis (IP) compared to those with TLE only (NIP) and healthy controls (HC), and to explore the associations between cortical parameters (area, thickness and volume), psychotic symptoms, and cognitive performance. METHODS: Twenty-two patients with IP (9 male; 10 hippocampal sclerosis, HS), 23 TLE nonpsychotic (NIP) patients (11 male; 13 HS) matched for duration of epilepsy and 20 HC participated. Surface-based morphometry (SBM) was used to measure cortical parameters. Cognition was examined in IP and NIP patients. Associations between cortical parameters and cognition were examined using linear mixed models adjusted by age, gender, and brain volume. KEY FINDINGS: IP patients had an earlier onset of epilepsy, more status epilepticus, and worse cognitive performance than NIP patients. In IP patients, cortical thickness was reduced in the inferior frontal gyrus (IFG), and their current IQ was associated with decreases in area, but not thickness, in regions of the frontotemporal cortex. SIGNIFICANCE: IP likely reflects the interplay of psychosis-related genetic factors and the cumulative effects of seizure activity on the brain. Cortical thinning in the IFG, a region implicated in schizophrenia, is likely to be related to seizure activity, whereas changes in IQ, associated with reductions in area of frontotemporal cortex, may be related to the presence of psychosis.

Non-randomized open trial of eicosapentaenoic acid (EPA), an omega-3 fatty acid, in ten people with chronic epilepsy.

This is a non-randomized open assessment of eicosapentaenoic acid (EPA) supplementation in ten people (five males) with refractory focal seizures. Each received 1000 mg of EPA daily for 3 months. Six people had fewer seizures during the supplementation period compared with baseline (range 12 to 59% reduction) and one other person had markedly reduced seizure severity. The mean reduction in seizure frequency was 16% (95% CI - 10% to 35%, p=0.26). With the small number of participants and open nature of the study, interpretation of the results is difficult, but a possible weak effect of EPA on seizures cannot be discounted. Further examination of EPA supplementation should be undertaken with larger numbers of people in controlled trials. Higher doses and longer duration of treatment should be considered.

Effect of early sleep apnoea treatment with adaptive servo-ventilation in acute stroke patients on cerebral lesion evolution and neurological outcomes: study protocol for a multicentre, randomized controlled, rater-blinded, clinical trial (eSATIS: early Sleep Apnoea Treatment in Stroke).

BACKGROUND: Sleep-disordered breathing (SDB) is highly prevalent in acute ischaemic stroke and is associated with worse functional outcome and increased risk of recurrence. Recent meta-analyses suggest the possibility of beneficial effects of nocturnal ventilatory treatments (continuous positive airway pressure (CPAP) or adaptive servo-ventilation (ASV)) in stroke patients with SDB. The evidence for a favourable effect of early SDB treatment in acute stroke patients remains, however, uncertain. METHODS: eSATIS is an open-label, multicentre (6 centres in 4 countries), interventional, randomized controlled trial in patients with acute ischaemic stroke and significant SDB. Primary outcome of the study is the impact of immediate SDB treatment with non-invasive ASV on infarct progression measured with magnetic resonance imaging in the first 3 months after stroke. Secondary outcomes are the effects of immediate SDB treatment vs non-treatment on clinical outcome (independence in daily functioning, new cardio-/cerebrovascular events including death, cognition) and physiological parameters (blood pressure, endothelial functioning/arterial stiffness). After respiratory polygraphy in the first night after stroke, patients are classified as having significant SDB (apnoea-hypopnoea index (AHI) > 20/h) or no SDB (AHI < 5/h). Patients with significant SDB are randomized to treatment (ASV+ group) or no treatment (ASV- group) from the second night after stroke. In all patients, clinical, physiological and magnetic resonance imaging studies are performed between day 1 (visit 1) and days 4-7 (visit 4) and repeated at day 90 ± 7 (visit 6) after stroke. DISCUSSION: The trial will give information on the feasibility and efficacy of ASV treatment in patients with acute stroke and SDB and allows assessing the impact of SDB on stroke outcome. Diagnosing and treating SDB during the acute phase of stroke is not yet current medical practice. Evidence in favour of ASV treatment from a randomized multicentre trial may lead to a change in stroke care and to improved outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02554487 , retrospectively registered on 16 September 2015 (actual study start date, 13 August 2015), and www.kofam.ch (SNCTP000001521).

[Sleep Disorders in Old Age]. / Schlafstörungen im Alter.

Sleep Disorders in Old Age Abstract. Sleep disorders increase with age. Older patients rarely complain about sleep disorders, therefore it is important to ask about sleep problems. Insomnias, sleep-disordered breathing and restless legs syndrome tend to increase with older age. It is important to consider that sleep disorders may be the first symptom of a depression, anxiety disorder or neurodegenerative disorders such as dementias. Many factors can influence sleep in old age: it is important to inquire after sleeping habits including naps during the day, medication and comorbidity. Treatment depends on the causes. Insomnias should be treated mainly with non-pharmacological means such as cognitive behaviour therapy.

Bryophyllum pinnatum in the treatment of restless legs syndrome: A case series documented with polysomnography.

Restless legs syndrome may seriously affect patients' sleep and quality of life, but established pharmacological therapy can often have severe side effects. Therefore, new therapeutic approaches such as well-tolerated preparations from the medicinal plant Bryophyllum pinnatum should be considered as alternatives. Their sedative and spasmolytic properties might contribute to improve patients' condition.

Mortality and morbidity rates are increased in people with epilepsy: is stress part of the equation?

People with epilepsy (PWE), particularly those with more severe seizures, are at risk of premature death. The contribution of deaths unrelated to epilepsy to this risk is likely to be significant. Recent studies indicate that comorbid conditions are similarly increased in PWE. The reason for these increases in unrelated deaths and comorbid conditions is unclear. In this article, we argue that having seizures is psychologically stressful, and that this stress can lead to a whole range of pathophysiological changes that may trigger various physical illnesses. Hence, psychological stress may be a significant factor contributing to the increase in mortality and comorbidity rates in PWE. This speculation is unlikely to be proven at this stage because of the complexity of the trials required. In PWE who continue to have seizures, more needs to be done to help them cope with the stress. Additionally, attention needs to be paid to improve nutritional status and physical fitness. These steps are likely to enhance the overall health of PWE and may reduce premature mortality and comorbidity rates.

A magnetization transfer imaging study in patients with temporal lobe epilepsy and interictal psychosis.

BACKGROUND: Findings from previous neuropathological and neuroimaging studies in patients with epilepsy and interictal psychosis have been inconclusive, and both focal and widespread brain abnormalities have been reported. Thus, further investigation with advanced in vivo magnetic resonance imaging (MRI) techniques, such as magnetization transfer imaging, capable of detecting more subtle brain abnormalities, is warranted. METHODS: Twenty patients with temporal lobe epilepsy and interictal psychosis were compared with 20 nonpsychotic patients. Patients were matched with respect to conventional MRI findings. Each group comprised of 10 patients with hippocampal sclerosis (6 left, 4 right) and 10 patients without focal lesions on MRI. A voxel-based analysis was used for the group comparisons. RESULTS: Voxel-based analysis revealed significant reductions of magnetization transfer ratio (an index of signal loss derived from magnetization transfer imaging) in the left superior and middle temporal gyri in the psychotic patients for the subgroup of patients with no focal lesions on MRI. There were no significant volumetric differences between the psychotic and nonpsychotic patients. CONCLUSIONS: Focal cortical magnetization transfer ratio abnormalities in the left temporal lobe unrelated to volume changes can be demonstrated in some temporal lobe epilepsy patients with interictal psychosis. Our findings might reflect subtle neuropathological abnormalities that are undetected by conventional MRI.

A neuropsychological study of patients with temporal lobe epilepsy and chronic interictal psychosis.

PURPOSE: To characterize the pattern of cognitive deficits in patients with temporal lobe epilepsy (TLE) and interictal (schizophrenia-like) psychosis and to examine the relationship between neuropsychological deficits and Magnetization transfer imaging. METHODS: Twenty patients with TLE and interictal psychosis were compared to 20 non-psychotic TLE patients. Patients were matched with respect to premorbid IQ, age and conventional MRI findings. A battery of neuropsychological tests was administered. The neuropsychological tests which showed significant group differences were used for correlational analysis with magnetization transfer ratio (MTR) which provides a quantitative measure of macromolecular structural integrity. RESULTS: Patients with interictal psychosis were significantly more impaired on executive and semantic memory tasks than the non-psychotic TLE group. Vocabulary test scores correlated significantly with MTR reduction in the left fusiform gyrus in the psychotic but not the non-psychotic group. DISCUSSION: In this study, patients with TLE and interictal psychosis were more cognitively impaired than non-psychotic TLE patients. Our findings suggest that the cognitive deterioration in these patients may occur as the illness progresses and the causes for this are probably multifactorial. Our study also provides further evidence that MTR may be useful in investigating structural correlates of cognitive impairment.

Neural correlates of de novo depression following left temporal lobe epilepsy surgery: a voxel based morphometry study of pre-surgical structural MRI.

PURPOSE: To investigate cerebral grey matter (GM) volumetric abnormalities in temporal lobe epilepsy (TLE) patients who develop de novo depression following TLE surgery using voxel-based morphometry (VBM). METHODS: We retrospectively examined pre-surgical grey matter (GM) volumes in 30 patients with TLE due to unilateral left-sided hippocampal sclerosis using 1.5-T MRI scan, which were segmented with optimised VBM parameters and normalised to a sample template using DARTEL, with SPM8 software. Voxel-wise GM differences between patients that developed de novo post-surgical depression (n=5) were compared with patients with no pre- or postoperative psychiatric diagnoses (n=25), using independent samples t-tests with age, gender and secondary generalised tonic-clonic seizures (SGTCS) as covariates (p<.001, unc). KEY FINDINGS: Reduced preoperative bilateral GM in orbitofrontal cortices (OFC) and ipsilateral cingulate gyrus and thalamus were significantly associated with the development of de novo depression within 4 years postoperatively. Further analyses revealed no differences in seizure freedom (ILAE 1 vs 2-6) or postoperative memory decline between the groups. SIGNIFICANCE: Although the development of postoperative de novo depression following TLE surgery is likely to be multi-factorial, our results suggest that bilateral OFC and ipsilateral cingulate gyrus and thalamic atrophy in left-sided TLE patients may play a modulatory role. Abnormalities in these areas have also been implicated in primary mood disorders. Prospective neuroimaging studies with larger cohorts are warranted to replicate these results, and further elucidate the neural correlates of de novo depression.

Erythrocyte and plasma fatty acid profiles in patients with epilepsy: does carbamazepine affect omega-3 fatty acid concentrations?

Fatty acids (FAs) determine membrane properties and may affect cardiac and neuronal function. In this study, FA profiles were determined in 56 patients with epilepsy who participated in a 12-week double-blind randomized trial of omega-3 FA supplementation (1 g eicosapentaenoic acid and 0.7 g docosahexaenoic acid daily). At baseline, subjects on carbamazepine (CBZ) had lower docosahexaenoic acid levels, lower levels of long-chain omega-3 FAs, and a lower Omega-3 Index (a risk factor for coronary heart disease mortality), whereas those on oxcarbazepine had higher total polyunsaturated FAs and a higher Omega-3 Index. Following omega-3 FA supplementation, the Omega-3 Index, eicosapentaenoic acid, and docosahexaenoic acid concentrations significantly increased. Patients on CBZ exhibited a less favorable FA profile, associated with a greater risk of coronary heart disease mortality. As arrhythmias are thought to be an important mechanism in coronary heart disease mortality and sudden unexplained death in epilepsy (SUDEP), the effect of CBZ effect in reducing omega-3 FAs might potentially explain some cases of SUDEP among patients prescribed CBZ.

Magnetisation transfer ratio of choline is reduced following epileptic seizures.

The purpose of this study was to characterise the concentration and magnetisation transfer ratio (MTR) of brain metabolites following epileptic seizures. Magnetic resonance spectroscopy was performed in 10 patients with temporal or extra-temporal lobe epilepsy as soon as possible after a seizure, with a second interictal scan between 1 and 3 days after the postictal scan and 10 healthy controls were scanned twice. Voxels (26 +/- 2 mL) were placed in the frontal lobe in all patients and controls, on the side of seizure focus in the patient group. Spectra were obtained using a modified PRESS sequence (TE 30 ms, TR 3 s, with three hard pulses offset from the water frequency by 2,500 Hz for MT presaturation). Mean metabolite concentrations and median metabolite MTRs of N-acetylaspartate (NAA), creatine, choline (Cho), myo-inositol (Ins) and glutamate plus glutamine were compared between the first and second scans in each group. A significant decrease in the MTR of Cho was seen postictally in the patient group, but the metabolite concentrations showed no significant difference between interictal and postictal scans and in the control group there was no difference between the two scans. Inter-group comparison showed significantly reduced concentrations of NAA and Ins in the patients. Reduced MTR of Cho indicates a shift from a bound to a more mobile fraction. These changes might indicate membrane perturbation in areas of seizure spread.

Diffusion tensor imaging findings and their correlation with neuropsychological deficits in patients with temporal lobe epilepsy and interictal psychosis.

PURPOSE: To examine frontotemporal white-matter integrity in patients with temporal lobe epilepsy (TLE) and interictal psychosis. METHOD: Patients with TLE and interictal psychosis (IP; n = 20) were compared with age-matched TLE patients without psychosis (NIP; n = 20). Patients had either no focal lesions or hippocampal sclerosis on conventional MRI. Complete diffusion tensor imaging (DTI) data were available in 18 IP and 20 NIP patients. A region-of-interest (ROI) approach was used to determine the DTI measures, fractional anisotropy (FA) and mean diffusivity (MD), in the middle frontal and middle temporal gyri. The relation between the DTI measures and neuropsychological tests previously identified as impaired in the IP group was examined. RESULTS: The IP group had significantly lower FA values in both frontal and temporal regions and significantly higher MD in bilateral frontal regions. We found that performance on some neuropsychological tests was significantly related to frontotemporal FA reductions. CONCLUSIONS: Our findings suggest that subtle abnormalities in the frontotemporal white matter of patients with interictal psychosis may be undetectable on conventional MRI. These abnormalities may contribute to the cognitive deficits detected in these patients.