Daily Attacks Research Articles

Trial of Galcanezumab in Prevention of Episodic Cluster Headache

BackgroundEpisodic cluster headache is a disabling neurologic disorder that is characterized by daily headache attacks that occur over periods of weeks or months. Galcanezumab, a humanized monoclonal antibody to calcitonin gene–related peptide, may be a preventive treatment for cluster headache.MethodsWe enrolled patients who had at least one attack every other day, at least four total attacks, and no more than eight attacks per day during a baseline assessment, as well as a history of cluster headache periods lasting at least 6 weeks, and randomly assigned them to receive galcanezumab (at a dose of 300 mg) or placebo, administered subcutaneously at baseline and at 1 month. The primary end point was the mean change from baseline in the weekly frequency of cluster headache attacks across weeks 1 through 3 after receipt of the first dose. The key secondary end point was the percentage of patients who had a reduction from baseline of at least 50% in the weekly frequency of cluster headache attacks at week 3. Safety was also assessed.ResultsRecruitment was halted before the trial reached the planned sample size of 162 because too few volunteers met the eligibility criteria. Of 106 enrolled patients, 49 were randomly assigned to receive galcanezumab and 57 to receive placebo. The mean (±SD) number of cluster headache attacks per week in the baseline period was 17.8±10.1 in the galcanezumab group and 17.3±10.1 in the placebo group. The mean reduction in the weekly frequency of cluster headache attacks across weeks 1 through 3 was 8.7 attacks in the galcanezumab group, as compared with 5.2 in the placebo group (difference, 3.5 attacks per week; 95% confidence interval, 0.2 to 6.7; P=0.04). The percentage of patients who had a reduction of at least 50% in headache frequency at week 3 was 71% in the galcanezumab group and 53% in the placebo group. There were no substantial between-group differences in the incidence of adverse events, except that 8% of the patients in the galcanezumab group had injection-site pain.ConclusionsGalcanezumab administered subcutaneously at a dose of 300 mg once monthly reduced the weekly frequency of attacks of episodic cluster headache across weeks 1 through 3 after the initial injection, as compared with placebo. (Funded by Eli Lilly; ClinicalTrials.gov number, NCT02397473.)

Difficult To Treat Recurrent Esophageal Dysphagia Due To Secondary Esophageal Motility Disorders: A 24 Weeks Follow Up Case Report

Limited data are available on the prevalence of esophageal motility disorders (OMD) with a suggested range of 4-12% in cases with dysphagia. The proposed pathophysiology is either impairment of inhibitory innervation or overactivity of excitatory innervation. The optimal treatment is not defined until now. This case represented one of the secondary OMD in a 70 years year diabetic patient with ischemic cardiomyopathy, who was complaining of recurrent daily intermittent dysphagia to solids and fluids, with a previous vague history of esophageal dilatation without available documentation. After endoscopy with multiple biopsies and barium imaging, the picture of the corkscrew esophagus was revealed. The patient, who was already on nitrates, failed to respond to twice-daily proton pump inhibitor for two months with a prokinetic drug, calcium channel blocker, and the first session of endoscopic esophageal dilatation. After the second session of dilatation, we add sodium alginate with the substitution of nitrates with sildenafil, and the patient reported a gradual improvement of dysphagia especially to fluids with decreasing in daily attacks. We learn from this case that there is a different patient-to-patient response, which necessitates the use of different treatment modalities even just switching between nitric oxide scavengers for each patient. Keywords: Case Report; Dysphagia; esophageal Motility Disorders.

Countering Right-Wing Populism: Transgressive Cosmopolitanism and Solidarity Movements in Europe

Countering Right-Wing Populism:Transgressive Cosmopolitanism and Solidarity Movements in Europe Kim Rygiel (bio) and Feyzi Baban (bio) Over the past several years, right-wing populist movements have emerged and strengthened across Europe and North America. Yet, at the same time, in response to growing xenophobia and racism, political mobilizations by refugees and migrants, as well as citizens working in solidarity with them, have also emerged, demanding human and labor rights, fair asylum processes, and mobility rights. We examine the emergence of grassroots solidarity initiatives in cities and towns such as Berlin, Copenhagen, Riace, Istanbul, and Gaziantep, which include arts and museum projects, kitchen hubs, and flat-sharing that foster pluralism and open community to newcomers. This essay examines these as transnational forms of solidarity, informed by notions of "transgressive cosmopolitanisms."1 It investigates these alternative sites as disruptive of hierarchical borders of belonging between newcomers (recently arrived migrants and refugees) and locals (nonmigrant residents), which thereby foster more inclusionary ways of living together. In the European context (e.g., Denmark, Germany, Italy, and Turkey), these movements are significant because they challenge the rigidity of thinking about national identities and belonging, coupled with restrictive immigration and refugee policies, both of which make it difficult for newcomers to establish themselves as members of the larger society. These movements provide much-needed social and cultural spaces where newcomers can establish networks with nonmigrant residents. The radical impact of these movements stems, first, from their resistance to the idea of homogeneous national identities, championed by right-wing movements but also prevalent in mainstream understandings about what it means to be German, Danish, Italian, or Turkish; and second, their ability to provide spaces and activities through which newcomers and locals can create new understandings of belonging. [End Page 1069] Countering Right-Wing Populism through Solidarity across Borders The "long summer of migration" to Europe in 20152—which included the arrival of over 3.5 million Syrians in Turkey and almost 1 million asylum seekers in Germany, many of whom were Syrian—has spurred two opposing movements. The first is the rise of right-wing populism fueling xenophobia and racism across Europe, and the second, the emergence of transnational solidarity movements with refugees and migrants that demand greater social justice and freedom of movement. In the first case, right-wing populist parties and movements across Europe have contributed to racism, antimigrant and refugee discourse, and xenophobia more broadly. The March 2018 Italian election saw the populist Five Star Movement win 32 percent of the vote, while the hard-right, antimigrant, Eurosceptic Northern League won another 18 percent.3 This election follows the ascendance of other far-right parties and movements, including France's Front National, Hungary's Fidesz Party, Austria's Freedom Party, and in Germany, the rise of the Alternative for Germany (AfD) and PEGIDA (the Patriotic Europeans Against the Islamisation of the West). Confronted with shocking images of thousands of refugees and migrants marching through the Balkan countries of Slovenia, Croatia, and Serbia in 2015, Hungary erected a barbed wire fence along its southern border with Serbia. The rise of antirefugee/antimigrant right-wing populism is not limited to Europe, however, as far-right groups are creating linkages between transnational white supremacy4 and "radical Europeanism."5 Ironically, however, despite making transnational linkages, such networks call for maintaining borders, whether national, racial, cultural, or religious. This ideology has led to violent attacks against others perceived to be different for reasons of race, religion, or sexuality, as seen, for example, in the nearly daily attacks on refugee shelters in response to German chancellor Angela Merkel's welcoming of refugees into Germany in 2015.6 Such movements can, therefore, no longer be dismissed as simply local or as existing on the margins of society; rather, this is a phenomenon we must contend with as activists, academics, and progressive citizens committed to fostering open and pluralistic communities. The second counter, cross-border movement is a strengthening of political mobilization by refugees and migrants, as well as citizens organizing in solidarity, demanding human rights and social justice, whether labor rights, housing, health care, and freedom of mobility, including the right to asylum.7 As part of...

Changes in serum BDNF levels after treatment of panic disorder patients

Aim: Panic disorder is a significant psychiatric disorder that more frequently occurs in women, with daily attacks such as fear of death, limiting the patient’s daily life. It is often associated with agoraphobia. The aim of this study was to investigate the relationship between BDNF levels and the clinical features of panic disorder.Material and Methods: The study was carried out between January 2015 and July 2015 with 42 female patients and 38 healthy females who were admitted to Psychiatry Outpatient Clinic. The patients who were diagnosed with panic disorder without agoraphobia included in the study. The Panic Disorder Severity Scale (PDSS) was applied to the patients. Serum BDNF was measured by sandwich ELISA.Results: The mean age of the 38 female patients was 35.1±11.5 years. The mean age of the control group of 38 healthy women was 34.9±9.82 years. Serum BDNF levels measured before treatment were significantly lower than BDNF levels measured after treatment (p 0.001). Serum BDNF levels measured before treatment were significantly lower than BDNF levels of the control group (p0.001). While there was a statistically significant negative correlation between BDNF levels and PDSS scores before treatment.Conclusion: Serum BDNF levels were significantly increased after treatment. The PDSS scores also decreased significantly after treatment. These results inform us about the effectiveness of the treatment. BDNF levels may also be considered as an indicator of the clinical follow-up of the panic disorder without agoraphobia.Keywords: Panic disorder; brain-derived neurotrophic factor; agoraphobia.

СОСТАВ ЖИРНЫХ КИСЛОТ И УРОВЕНЬ ИХ МЕТАБОЛИТОВ ПРИ ЧАСТИЧНО КОНТРОЛИРУЕМОЙ БРОНХИАЛЬНОЙ АСТМЕ НА ФОНЕ КОМПЛЕКСНОГО ЛЕЧЕНИЯ С ПРИМЕНЕНИЕМ МИЛЛИМЕТРОВОЙ ТЕРАПИИ

To assess the anti-inflammatory effect of millimeter therapy in the treatment of partially controlled asthma, the fatty acid composition of erythrocyte membranes and their oxygenase derivatives were studied. Eighty-five subjects aged 18 to 45 years old were examined, 60 of them were diagnosed with partially controlled asthma and 25 were a control group, which consisted of conditionally healthy subjects without bronchopulmonary pathology. Two study groups were formed. Patients of the 1st group (n=30) received only basic medical treatment: inhalation glucocorticosteroid and β2-agonists of short action on demand. Patients of the 2nd group (n=30) underwent complex treatment: basic medical treatment in combination with millimeter therapy according to the developed technique. Clinical symptoms (frequency of nocturnal and daily asthma attacks per week, severity of cough, need for short-acting bronchodilators during the day), results of the asthma symptom control questionnaire (ACQ-5 test), lung function, composition of fatty acid (FA) in erythrocyte membranes, level of eicosanoids were assessed. The dynamics of clinical-functional and laboratory indicators in patients was evaluated one month after the start of treatment. The study established a modification of FA erythrocyte membranes composition, characterized by an increase in the proportion of some representatives of saturated and monounsaturated FA, increased production of arachidonic acid and its cyclooxygenase and lipoxygenase metabolites (thromboxane B2, leukotriene B4) against the background of deficiency of eicosapentaenoic and docosapentaenoic acids. A significant decrease in the level of oxygenated derivatives of fatty acids in the blood plasma of patients was revealed against the background of positive dynamics of clinical course of the disease in the 2nd group receiving complex treatment, which indicates the normalization of metabolic transformations of oxygenated derivatives of fatty acids, and as a consequence the extinction of allergic inflammation under the influence of electromagnetic waves of the millimeter range of extremely high frequency.

Melatonin for preventing primary headache: A systematic review.

The aim of this study was to assess the effectiveness and safety of melatonin for primary headache. This systematic review following the Cochrane Handbook for Systematic Reviews of Interventions recommendations and PRISMA Statement. Four randomized controlled trials were included (351 participants). According to the GRADE approach the quality of evidence was very low. The use of melatonin for migraine showed that (i) reduced the number of days with pain and the analgesic consumption when compared with placebo, (ii) no benefits on headache intensity, number of headache days and analgesics consumption when compared with amitriptyline, (iii) reduced the number of analgesic consumption, the attack frequency and the headache intensity when associated with propranolol plus nortriptyline vs placebo plus propranolol plus nortriptyline, and (iv) no difference for any of the interest outcomes when associated with propranolol plus nortriptyline vs sodium valproate plus propranolol plus nortriptyline. The use of melatonin for cluster headache when compared with placebo showed a reduction in the daily number of analgesic consumption and no difference in the number of daily attacks. Adverse events were poorly reported by all of the studies. This review found that so far there are few clinical trials, with poor methodological quality about melatonin for primary headaches. The available evidence is not sufficient to support the use of melatonin in clinical practice for this population. Further research is still necessary for assess its effects (benefits and harms) for primary headaches patients. Number of Protocol registration in PROSPERO database: CRD42017067105 (available at https://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42017067105) .

Altered Spontaneous Brain Activity in Patients With Idiopathic Trigeminal Neuralgia: A Resting-state Functional MRI Study.

Objectives:To identify the changes of local coherence and intrinsic brain activity in resting-state idiopathic trigeminal neuralgia (ITN) patients by using regional homogeneity (ReHo) and fractional aptitude of low-frequency fluctuation (fALFF) analysis.Methods:ReHo and fALFF were analyzed in 23 ITN patients and 23 age-matched and sex-matched pain-free controls to detect the functional abnormality in the brains of ITN patients. Correlations between ReHo and fALFF were analyses. ITN pain intensity were also assessed in the ITN group.Results:Compared with pain-free controls, ITN patients exhibited significantly abnormal ReHo and fALFF in several brain regions, including the cerebellum, cingulate cortex, temporal lobe, putamen, occipital lobe, limbic lobe, precuneus, insula, medial, and superior frontal gyrus compared with healthy controls. Correlation analysis showed that ReHo values of several altered brain areas positively correlated with visual analog scale values. But no correlation was found between fALFF and visual analog scale.Discussion:Our results showed that ITN patients exhibited significantly abnormal spontaneous brain activity in several brain regions that are involved in pain modulation and perception. The present study reflects the maladaptive process of daily pain attacks and may enhance the understanding of how chronic pain affects local intrinsic brain activity.

Clinical Manifestations and Amplitude-integrated Encephalogram in Neonates with Early-onset Epileptic Encephalopathy.

Background:The patients with early-onset epileptic encephalopathy (EOEE) suffer from neurodevelopmental delay. The aim of this study was to analyze the clinical manifestations and amplitude-integrated encephalogram (aEEG) characteristics of infants with EOEE with onset within the neonatal period, to make early diagnosis to improve the prognosis.Methods:One-hundred and twenty-eight patients with neonatal seizure were enrolled and followed up till 1 year old. Sixty-six neonates evolved into EOEE were as the EOEE group, the other 62 were as the non-EOEE (nEOEE) group. Then we compared the clinical and aEEG characteristics between the two groups to analyze the manifestations in neonates with EOEE.Results:Compared to the nEOEE group, the incidence of daily seizure attacks, more than two types of convulsions, more than two antiepileptic drugs (AEDs) application, severely abnormal aEEG background, absence of cyclicity, and more than two seizures detection were significantly higher in the EOEE group (P < 0.05) (97% vs. 54.8%; 30.3% vs. 14.5%; 97.0% vs. 25.4%; 39.4% vs. 3.2%; 57.6% vs. 9.7%; and 56% vs. 3.2%, respectively). Severely abnormal background pattern (odds ratio [OR] = 0.081, 95% confidence interval [CI]: 0.009–0.729, P = 0.025) and more than two seizures detection by aEEG (OR = 0.158, 95% CI: 0.043–0.576, P = 0.005) were the independent risk factors for the evolvement into EOEE. The upper and lower margins of active sleep (AS) and quiet sleep (QS) were significantly higher in EOEE group than those of the control group (P < 0.05) (34.3 ± 13.6 vs. 21.3 ± 6.4; 9.9 ± 3.7 vs. 6.7 ± 2.2; 41.2 ± 15.1 vs. 30.4 ± 11.4; and 11.9 ± 4.4 vs. 9.4 ± 4.0; unit: μV, respectively). AS upper margin was demonstrated a higher diagnostic specificity and sensitivity for EOEE than another three parameters according to the receiver operating characteristic curves; the area under the curve was 0.827.Conclusions:The clinical characteristics of the neonatal seizure which will evolve into EOEE were more than two AEDs application, high seizure frequency (daily attack), and more than two types of the seizure. Significant high voltage, severely abnormal background, absence of cyclicity, and more than two seizures detected on aEEG were the meaningful indicators to the prediction of EOEE.

Actazolamide to treat congenital myopathy caused by SCN4A mutation

Objective: SCN4A encodes the alpha subunit of the skeletal muscle voltage-gated sodium channel, vital for the generation and propagation of the muscle action potential and muscle contraction. Sodium channel dysfunction typically results in myotonia and periodic paralysis. Acetazolamide is a common treatment for these disorders. Recently, SCN4A mutations have also been associated with congenital myopathy. We sought to ascertain if acetazolamide could be beneficial in an individual with SCN4A congenital myopathy. Methods: Clinical assessment pre and post acetazolamide therapy. Genetic analysis was performed at the Neurogenetics Unit, National Hospital for Neurology and Neurosurgery as provided by the Channelopathy Highly Specialised National Service for rare disease. Results: We present a 16 year old girl diagnosed with congenital myopathy due to compound heterozygous SCN4A mutations (c.311G > Ap.Arg104His, c.3403C > Tp.Arg1135cys). She has been on non-invasive ventilation at night since age 6 and had a scoliosis repair age 12. From age 8 she has been taking slow release salbutamol which resulted in overall improvement in limb function but from age 11 she began to complain of daily episodic leg weakness usually after school. Acetozolamide was started in July 2015 at a dose of 62.5 mg bd and has gradually been increased to 250 mg in the morning and 125 mg at night. Since starting the Acetozolamide there has been an improvement in overall levels of fatigue and a cessation of the daily attacks of leg weakness. The only side effects she experienced were tingling of the mouth, hands and feet on initiation of treatment which subsequently resolved. Conclusion: From this case Acetozolamide appears to be a promising agent in maintaining muscular function in those with SCN4A related congenital myopathy. This may be mutation specific as her point mutation (c.311G > Ap.Arg104His, c.3403C > Tp.Arg1135cys) alters channel function in a manner comparable to other periodic paralysis mutations.

Small temporal pole encephaloceles in children with presumed nonlesional temporal lobe epilepsy

Objective: Temporal lobe epilepsy (TLE) is the one of most common form of focal epilepsy. Children with intractable TLE epilepsy undergo presurgical evaluations for resective treatment. The cases are considered “nonlesional’’ if brain magnetic resonance imaging (MRI) shows no structural abnormality and they sometimes encounter invasive procedures. We describe two patients, initially thought to have “lesion negative” refractory TLE, in whom the recognition of a small anterior temporal encephalocele by close inspection of imaging altered the follow up strategy. Case Presentation: Case 1: 12-year-old girl, focal seizures began at age 10 years, manifesting as no reduced awareness, contractions in the corner of the mouth, and head version. At the time of assessment the patient was having multiple daily attacks. Two antiepileptic drugs in various doses and combinations had failed to control seizures. Early childhood development and schooling were unremarkable. Febrile seizures had not occurred. Video–electroencephalography (EEG) monitoring captured ten typical seizures, all originating from the right temporal region. Prior imaging was reported normal. The current brain MRI has showed small right anterior temporal tip encephalocele through a congenital defect in the sphenoidal bone. She is now a epilepsy surgery candidate. Case 1: 15-year-old girl, discognitive seizures began at age 6 years characterized by a rising abdominal sensation and impaired consciousness. Seizures continued weekly with no evolving to bilateral convulsive seizures, despite trials of two anticonvulsants in various doses and combinations. Febrile seizures had not occurred. Routine EEG showed interictal epileptiform activity in left temporal region. Prior imaging was reported normal. The current brain MRI has showed bilateral temporal tip encephalocele greater on the left. She will be hospitalized for phase I epilepsy surgery evaluations. Conclusion: We would like to present this cases to emphasize the discovery of an occult lesion such as an encephalocele markedly alters treatment opinions in children.

Regulation of neutrophil functions through inhibitory receptors: an emerging paradigm in health and disease.

Neutrophils are the most abundant subset of leukocytes and play a crucial role in the immune responses against the daily pathogen attacks faced by the host. Neutrophils exhibit several functions for fighting microbes, including the release of granules containing highly toxic molecules, the production of reactive oxygen species and inflammatory cytokines as well as NETosis. Therefore, immune responses mediated by neutrophils must be tightly regulated to protect the host from pathogen assaults without inducing detrimental inflammation and tissue damage. There is now compelling evidence showing that neutrophils express various inhibitory receptors that specifically control their functions. Some of these inhibitory receptors are contained in the membrane of granules and rapidly move to the cell surface upon neutrophil stimulation. This fast upregulation of inhibitory receptors is an efficient way to rapidly enhance inhibitory signals and increase the neutrophil activation threshold. However, because of their ability to attenuate the immune responses of neutrophils, the inhibitory receptors are attractive target for pathogens. This review discusses these various aspects with a particular emphasis on the regulation of neutrophil behavior through immunoreceptor tyrosine-based inhibition motif (ITIM)-bearing inhibitory receptors belonging to LILR and SIGLEC multi-gene families in humans and animal models.

Altered regional homogeneity of spontaneous brain activity in idiopathic trigeminal neuralgia.

The pathophysiology of idiopathic trigeminal neuralgia (ITN) has conventionally been thought to be induced by neurovascular compression theory. Recent structural brain imaging evidence has suggested an additional central component for ITN pathophysiology. However, far less attention has been given to investigations of the basis of abnormal resting-state brain activity in these patients. The objective of this study was to investigate local brain activity in patients with ITN and its correlation with clinical variables of pain. Resting-state functional magnetic resonance imaging data from 17 patients with ITN and 19 age- and sex-matched healthy controls were analyzed using regional homogeneity (ReHo) analysis, which is a data-driven approach used to measure the regional synchronization of spontaneous brain activity. Patients with ITN had decreased ReHo in the left amygdala, right parahippocampal gyrus, and left cerebellum and increased ReHo in the right inferior temporal gyrus, right thalamus, right inferior parietal lobule, and left postcentral gyrus (corrected). Furthermore, the increase in ReHo in the left precentral gyrus was positively correlated with visual analog scale (r=0.54; P=0.002). Our study found abnormal functional homogeneity of intrinsic brain activity in several regions in ITN, suggesting the maladaptivity of the process of daily pain attacks and a central role for the pathophysiology of ITN.

Impact of symptom management training among asthmatic children and adolescents on self-efficacy and disease course

Purpose: The study was conducted to examine the effect of a training program provided to asthmatic children/adolescents on disease course and self-efficacy. Methods: This prospective study consisted of both experimental and control subjects. The study population was composed of children/adolescents aged 10–18 years, who presented at Health Centers within Tokat province with asthma and who were currently using inhaler treatments. The study sample included 40 patients each in both the control and experimental groups. Asthmatic Child Information Form, Disease Evaluation Form, Peak Expiratory Flow Rate Evaluation Form and an Asthmatic Child/Adolescent Self-Efficacy Scale were used to collect data on research outcomes. Data were statistically analyzed with paired sample t-test, McNemar’s test, independent samples t-test. Results: A significant increase in mean self-efficacy score was observed in the experimental group following training sessions. The experimental training was also associated with a reduction in asthma symptoms, less limitations to daily function and fewer attacks following physical activity relative to the control subjects. The children/adolescents in the experimental group were more conscious of the symptoms of asthma attacks and used preventive and rescue medications regularly, and reported fewer absences from school and fewer emergency room visits (p < 0.05). The average peak expiratory flow rate was 62.5% in the experimental group. After training, there were significant decreases in the number of attacks and the need of increasing inhaler doses in the experimental group. Conclusions: The study results show that the training program is effective in increasing self-efficacy and improving asthma symptoms among children/adolescents. Nurses should offer the training program to support children/adolescents during asthma attacks, and encourage the development of self-efficacy

Cluster headache.

Cluster headache.

Ramelteon in the Prophylaxis of Chronic Cluster Headache- Case Report

Cluster headache is a primary headache characterized by severe pain with most attacks occurring during sleep. This is a case report on the use of ramelteon as a treatment for chronic cluster headache. A 42-year-old businessman, who had been experiencing episodic cluster headaches for 10 years, was diagnosed with chronic cluster headache in the past year during which time his activities of daily living had been greatly reduced because of daily cluster headache attacks. We initiated treatment with ramelteon (8 mg/day) prophylactically before sleep, and his average attack frequency per day after taking the drug was less than that before taking the drug. The elimination half-life of ramelteon is typically under 2 h, whereas that of melatonin is typically 30 min. This difference in the elimination half-life may have caused the better response to ramelteon treatment than to melatonin. We conclude that ramelteon may be useful as a new agent in both the prevention and prophylaxis of chronic cluster headache, when attacks occur at the same time during the night and that cluster headache is related to circadian rhythm.

The complex impact of five years of stress related to life-threatening events on pregnancy outcomes: A preliminary retrospective study

ObjectiveTo study the impact of chronic, life-threatening stressors in the form of daily missile attacks, for five consecutive years, on pregnancy outcomes. MethodCharts of deliveries from two neighboring towns in the south of Israel, covering the years 2000 and 2003–2008, were reviewed retrospectively. One city had been exposed to missile attacks, while the other was not. For each year, 100 charts were chosen at random. ResultsSignificant association was found between exposure to stress and frequency of pregnancy complications (P=0.047) and premature membrane rupture (P=0.029). A more detailed analysis, based on dividing the stressful years into three distinct periods: early (2003–2004), intermediate (2005–2006) and late (2007–2008), revealed that preterm deliveries were significantly more frequent (P=0.044) during the intermediate period, as was premature membrane rupture during the late period (P=0.014). ConclusionExposure to chronic life-threatening stress resulted in more pregnancy complications and in particular more premature membrane ruptures. The impact was most significant during the middle period of the 5-year-exposure to the stressor. Hence it seems that factors of duration and habituation may play a role in the impact of chronic, life-threatening stressors on pregnancy.

High-dose olanzapine for bipolar depression: proceed with caution.

To the Editor: High-dose olanzapine has gained momentum as an effective pharmacotherapy in individuals diagnosed with treatment-resistant schizophrenia, yet there is little evidence regarding its safety.1–4 Olanzapine is also indicated for the treatment of bipolar disorder; however, few guidelines are available regarding dosing of olanzapine for individuals with treatment-resistant bipolar disorder. The following case report highlights the need for increased guidance in the management of treatment-resistant bipolar disorder. Case report. Mr A is a white man with a long history of psychiatric disorders, specifically bipolar I disorder (DSM-IV-TR criteria). He also has a diagnosis of posttraumatic stress disorder and a history of alcohol dependence and cannabis use (DSM-IV-TR criteria); however, he is reported to have not used cannabis for over 2 years. Mr A complained of severe mood swings including daily anxiety and panic attacks several times weekly and paranoia. After failing treatment with several other mood stabilizers and antipsychotic medications and declining treatment with clozapine, olanzapine was prescribed by his primary care provider. Olanzapine was increased over the course of 4 weeks to 80 mg/d (40 mg oral twice a day) to control his symptoms. Mr A reported that the anxiety and panic attacks did not occur as frequently; however, he was now experiencing erectile dysfunction, which was believed to be due to high-dose olanzapine. Despite the erectile dysfunction, Mr A asked to maintain high-dose olanzapine, as he felt the benefits outweighed the risks. Over the following 2 weeks, his depressive symptoms fluctuated, and Mr A reported that he was still struggling with posttraumatic stress disorder but managing better with other symptoms. At the time of his presentation to the inpatient psychiatry ward, 5 weeks after the prescription of high-dose olanzapine, Mr A reported increasing anxiety, depression, paranoid delusions, guilt, and suicidal ideation. He also described symptoms similar to hyperreligiosity. Mr A denied use of any illicit drugs or alcohol prior to arriving at the hospital. The olanzapine dose was reduced to 40 mg/d (20 mg oral twice a day). Following this reduction, he showed immediate improvement in symptoms and felt significantly better. Mr A was provided with education regarding the benefits and risks of high-dose olanzapine and reported that this was “new information,” and he had not been adequately told of the dangers. At discharge, Mr A was stable on 40 mg/d of olanzapine. Although some studies have indicated the benefits of high-dose olanzapine, the dose is typically in the range of 20–60 mg/d rather than 80-mg/d, as was prescribed to Mr A.1,2 Greater guidance is needed to clarify procedures involved in dose escalation of olanzapine and monitoring of side effects. Further clinical trials highlighting the benefits and risks of high-dose olanzapine with a foundation on understanding mechanisms of treatment resistance should be a priority.

Regional homogeneity abnormalities in patients with tension-type headache: a resting-state fMRI study.

Tension-type headache (TTH) is the most prevalent type of primary headache. Many studies have shown that the pathogenesis of primary headache is associated with fine structural or functional changes. However, these studies were mainly based on migraine. The present study aimed to investigate whether TTH patients show functional disturbances compared with healthy subjects. We used restingstate functional magnetic resonance imaging (fMRI) and regional homogeneity (ReHo) analysis to identify changes in the local synchronization of spontaneous activity in patients with TTH. Ten patients with TTH and 10 age-, gender-, and education-matched healthy controls participated in the study. After demographic and clinical characteristics were acquired, a 3.0-T MRI system was used to obtain resting-state fMRIs. Compared with healthy controls, the TTH group exhibited significantly lower ReHo values in the bilateral caudate nucleus, the precuneus, the putamen, the left middle frontal gyrus, and the superior frontal gyrus. There was no correlation between mean ReHo values in TTH patients and duration of TTH, number of attacks, duration of daily attacks, Visual Analogue Scale score, or Headache Impact Test-6 score. These results suggest that TTH patients exhibit reduced synchronization of neuronal activity in multiple regions involved in the integration and processing of pain signals.

Familial hemiplegic migraine and spreading depression.

Familial hemiplegic migraine (FHM) is an autosomal dominantly inherited subtype of migraine with aura, characterized by transient neurological signs and symptoms. Typical hemiplegic migraine attacks start in the first or second decade of life. Some patients with FHM suffer from daily recurrent attacks since childhood. Results from extensive studies of cellular and animal models have indicated that gene mutations in FHM increase neuronal excitability and reduce the threshold for spreading depression (SD). SD is a transient wave of profound neuronal and glial depolarization that slowly propagates throughout the brain tissue and is characterized by a high amplitude negative DC shift. After induction of SD, S218L mutant mice exhibited neurological signs highly reminiscent of clinical attacks in FHM type 1 patients carrying this mutation. FHM1 with ataxia is attributable to specific mutations that differ from mutations that cause pure FHM1 and have peculiar consequences on cerebellar Cav2.1 currents that lead to profound Purkinje cell dysfunction and neuronal loss with atrophy. SD in juvenile rats produced neuronal injury and death. Hormonal factors involved in FHM affect SD initiation and propagation. The data identify SD as a possible target of treatment of FHM. In addition, FHM is a useful model to explore the mechanisms of more common types of migraine.

Cluster headache: a challenging headache

Introduction: cluster headaches (CS) are a subtype of primary headache disorder characterized by daily pain attacks of 15-180 minutes for weeks to months, usually interspersed with periods of remission. Painful crises are very intense, of periorbital or orbital location, associated with symptoms of autonomic dysfunction. Despite its unique clinical presentation, CS remains under-recognized and underdiagnosed. Objectives: To describe and discuss the diagnostic and therapeutic challenges of CS based on clinical cases. Methods: this is a series of five cases of CS under clinical monitoring. Results: Of the 467 patients treated at the neurological clinic five had a diagnosis of CS, corresponding to 1.07% of the total. The clinical presentation varied little in relation to the description in the literature; it affected predominantly men, episodically. Time elapsed between onset and diagnosis was usually long. Conclusion: Even in a tertiary care neurological center, the number of diagnosed patients is small, which reflects on ignorance about CS and contributes to late diagnosis and lack of specific treatment.