The premonitory symptoms (prodrome): a tertiary care study of 893 migraineurs

OBJECTIVES: This study of premonitory symptoms in migraine was performed to document the frequency, duration, and types of symptoms in a large group of migraine patients. BACKGROUND: Prodrome importance continues to be debated. Intervention early in the migraine attack is assuming more importance and necessitates better knowledge of the prodrome. METHODS: A total of 893 migraine patients (IHS 1.1-1.7) were evaluated at first visit. Prodrome frequency, duration, and characteristics were analyzed in the total migraine population IHS 1.1-1.7 and IHS 1.1-1.6 migraine. RESULTS: A total of 32.9% of IHS migraine 1.1-1.6 patients reported prodrome symptoms with an average of 9.42 hours. IHS 1.1-1.7 migraine reported 29.7% and 6.8 hours, respectively. The most commonest symptoms were tiredness, mood change, and gastrointestinal symptoms; all three of these symptoms were present together in 17% of the patients with prodrome. The duration of prodrome was less than 1 hour in 45.1%, 1-2 hours in 13.6%, 2-4 hours in 15.0%, 4-12 hours in 13.1%, and greater than 12 hours in 13.2%. IHS 1.1-1.7 patients showed similar findings. IHS 1.1-1.6 patients with prodrome differed from patients without prodrome in having more triggers as a whole (P <.01), more individual triggers including alcohol (P <.01), hormones (P <.01), light (P <.001), not eating (P <.05), perfume (P <.01), stress (P <.01), and weather changes (P <.05), a longer duration of aura (P <.05), longer time between aura and headache (P <.05), more aura with no headache (P <.05), longer time to peak of headache (P <.05), longer time to respond to triptan (P <.05), longer maximum duration of headache (P <.05), and more headache associated nausea (P <.05), more headache associated running of the nose or tearing of the eyes (P <.05), more postdrome syndrome (P <.05), and longer duration of postdrome syndrome (P <.001). CONCLUSIONS: This study provides a portrait of prodrome in a large cohort of patients. It highlights differences between patients with prodrome and patients not having prodrome, and it draws attention to the potential of preventing the headache phase of the acute migraine attack.     

A H(2)(15)O positron emission tomography study on mental imagery of movement sequences--the effect of modulating sequence length and direction

Motor imagery is a state of mental rehearsal of single movements or movement patterns and has been shown to recruit motor networks overlapping with those activated during movement execution. We wished to examine whether the brain areas subserving control of sequential processes could be delineated by pure mental imagery, their activation levels reflecting the processing demands of a sequential task. We studied six right-handed volunteers (39.0 +/- 14 years) with H(2)(15)O positron emission tomography (PET) while they continuously mentally pursued with their right hand one of five sequences differing in complexity (i.e., increases in sequence length, single-finger repetitions, and reversals). Conditions were repeated twice, alternating with two rest scans. Each imagined single motor element was paced at a frequency of 1 Hz. Significant activation increases (P < 0.05, corrected) associated with imagination of right finger movement sequences (conditions I to V combined)--compared to the rest condition--were observed in left sensorimotor cortex (M1/S1) and the adjacent inferior parietal cortex. Further activation increases (P < 0.001, uncorrected) occurred in bilateral dorsal premotor (PMd) cortex, left caudal supplementary motor area, bilateral ventral premotor cortex, right M1, left superior parietal cortex, left putamen, and right cerebellum. Activation decreases occurred in bilateral prefrontal and right temporo-occipital cortex. Activation increases that correlated with sequence complexity were observed only in specific areas of the activated network, notably in left PMd, right superior parietal cortex, and right cerebellar vermis (P < 0.05, corrected). In conclusion, our study, by varying the sequence structure of imagined finger movements, identified task-related activity changes in parietopremotor-cerebellar structures, reflecting their role in mediating sequence control.     

Cerebral blood flow and CO2 reactivity in interictal migraineurs: a transcranial Doppler study

There is still some controversy about alterations in velocity of blood flow and in cerebral vasomotor reactivity of intracranial arteries in migraineurs during the interictal phase. By means of simultaneous bilateral transcranial Doppler ultrasonography we, therefore, assessed intracranial blood flow velocities and cerebrovascular reactivity to carbon dioxide of all three basal brain arteries in 20 migraineurs during the interictal phase and 30 nonheadache-prone control subjects. Mean blood flow velocities were higher in migraineurs than in controls in all three arteries on both sides, with a significant difference (P < 0.05) for the right anterior cerebral artery and middle cerebral artery under basal conditions and for the right posterior cerebral artery during hypercapnia. Similarly, the cerebrovascular reactivity to carbon dioxide was always higher in patients than in controls, with a significant difference for the left anterior and the right middle cerebral arteries (P < 0.05) and the right posterior cerebral artery (P < 0.01). The broad overlap of cerebrovascular blood flow velocities and CO2 reactivities in patients and controls precluded identification of values diagnostic of migraine. Nevertheless, transcranial Doppler ultrasonography offers the opportunity to noninvasively monitor cerebral blood flow parameters and, therefore, represents a valuable tool for vascular research in migraine.     

Osmophobia and taste abnormality in migraineurs: a tertiary care study

OBJECTIVES: This study assesses osmophobia and taste abnormality for the first time in a large sample of migraine patients. METHODS: Seven hundred and twenty seven migraineurs were evaluated. Osmophobia, taste abnormality, and perfume or odor trigger were graded from 0 to 3. RESULTS: In patients with data, 24.7% of 673 patients complained of osmophobia (12.5% occasional, 7% frequent, and 5.2% very frequent) and 24.6% of 505 of taste abnormality (13.5% occasional, 6.1% frequent, and 5.0% very frequent). Perfume or odor trigger of acute migraine occurred in 45.5% of 724 patients (22.7% occasional, 10.2% frequent, and 12.6% very frequent). Perfume or odor trigger was associated with osmophobia in 61.5% and taste abnormality 62.1%. Osmophobia without taste abnormality occurred in 28.3% and taste abnormality without osmophobia in 40.3%. A greater percentage of females than males had osmophobia (25.7 vs. 17.5), taste abnormality (25.4 vs. 17.9), and perfume or odor trigger (49.3 vs. 22.1), all P<.0001. CONCLUSIONS: Osmophobia and taste abnormality occur in about one quarter of migraineurs during an acute migraine attack while perfume or odor trigger migraine in almost 50% of patients. Osmophobia and taste abnormality in the acute migraine attack, as well as perfumes or odor as a migraine trigger, are more common in females than in males.     

Migraine pain location: a tertiary care study of 1283 migraineurs

OBJECTIVES: This study of headache location in migraine was performed (1) to document the location of pain in a large group of migraine patients and (2) to assess the impact of different types of migraine, gender, aura, and headache features on the location of the headache. BACKGROUND: The literature documenting the location of the pain of acute attack of migraine is sparse. METHODS: A total of 1283 migraine patients (ICHD, 2004, 1.1, 1.2, 1.5.1, and 1.6) were evaluated at the 1st visit. Headache location and character were graded on a scale of 0 to 3 with 0 being none and 3 the most. Triggers were graded on a frequency scale of 0 to 3; 0 = none; 1 = less than 1/3 of time; 2 = between 1/3 and 2/3 of time; 3 = greater than 2/3 of time. Other headache features and medication responsiveness, were also recorded. Patients were stratified by migraine type and headache frequency. Combined and isolated locations, and the impact of age, gender, headache frequency, migraine types, and aura were addressed. Unremitting headache was excluded. RESULTS: Migraine patients reported that the highest location frequencies were in the eyes (67.1%), temporal (58.0%), and frontal (55.9%). The lowest were diffusely (17.5%) and vertex (24.1%). The intermediate were in the occipital (39.8%) and neck areas (39.7%). Other migraine types were remarkably similar. Hemi-cranial location was present in 66.6% of patients, 71.2% in episodic migraine and 61.4% in chronic migraine, 67.2% in females and 63.2% in males, 59.7% in migraine without aura and 68.9% in migraine with aura 100% of the time. Headaches were reported on the right side in 27.3%, left side 24.3%, both sides 23.7%, either side 15.0%, and in the middle of the head in 4.6% of cases. Significant differences in headache location were seen only within migraine and not other migraine types. Headache location was not correlated with lifetime duration of migraine, prodrome, response to triptan, intensity, time to peak of headache, recurrence frequency, and time to recurrence. CONCLUSIONS: This study provides a detailed documentation of headache location in a large cohort of patients. The commonest locations are the orbital, frontal, and temporal areas and least common sites being diffuse and the vertex. A single location is infrequent. Hemi-cranial location is present in two thirds of subjects and a quarter each are on the left side, right side, and both sides. The locations of the headache are very similar in different migraine types, but there are some differences. Under age 21 and older patients tended to show some differences in location and side. Location differences are seen with gender, headache frequency, and aura. Location shows many correlations with triggers and headache features.     

On electrochemistry of metal–organic framework Zn2(EDTA)(H2O)

Metal–organic compounds (MOFs) are a class of substances composed of metal ions or clusters coordinated to organic ligands to form one-, two-, or three-dimensional structures. Due to their high porosity, excellent adsorption and catalytic activity, as well as the possibility of simultaneous implementation of various charge accumulation mechanisms, they can be used as electrode materials for metal-ion batteries. However, a significant disadvantage is that most MOFs have a low electrical conductivity, and the production of conductive MOFs is a costly, time-consuming and technically difficult process. In this work, we developed a method for synthesizing the Zn₂(EDTA)(H₂O) MOF composite and studied the possibility of using it as an anode material for sodium-ion batteries based on aqueous electrolytes. The structure and morphology of the compound was studied using XRD, IR, TGA and SEM. Using cyclic voltammetry, the electrochemical characteristics of the organometallic framework in alkaline electrolytes 1, 10 M NaOH, as well as in saturated aqueous electrolyte NaClO₄, were evaluated. It has been established that the studied compound does not give a satisfactory electrochemical response in aqueous electrolytes (both in alkaline and neutral media) due to the strong degradation of the electrode material, which is associated with the high solubility of this MOF representative. Cyclic voltammetric studies showed the presence of two redox processes due to the release of metallic zinc from an electrolyte solution, where two forms of zinc exist in equilibrium (the ZnEDTA complex and the free zinc cation). Therefore, we concluded, it is not possible to use this material as an anode for water-based sodium-ion batteries in contrary to a published research study.

Zn₂(EDTA)(H₂O) irreversibly decomposes in both neutral (sat. NaClO₄) and alkali (NaOH) aqueous electrolytes with formation of various Zn complexes.     

Changes of cerebrovascular response to visual stimulation in migraineurs after repetitive sessions of somatosensory stimulation (acupuncture): a pilot study

OBJECTIVES: To evaluate the effect of repetitive somatosensory stimulation (acupuncture) on cerebrovascular response in migraineurs by functional transcranial Doppler. METHODS: Changes of cerebral blood flow velocity in the right posterior and left middle cerebral arteries were measured by functional transcranial Doppler during visual stimulation (flickering light over 57 seconds) in 10 migraineurs before and after 10 acupuncture sessions. The same stimulation paradigm was performed in 10 control subjects. Cerebral blood flow velocity data were analyzed with a previously validated technique based on automated stimulus-related averaging. To evaluate the clinical effect of the treatment, a headache diary monitored the frequency and intensity of the migraine attacks. A positive treatment effect was defined as a reduction of at least 50% in the attack frequency or the mean headache intensity (or both). RESULTS: Before treatment, migraineurs showed overshooting cerebral blood flow velocity changes at the beginning and at the end of the stimulation and a delayed decline to baseline compared with control subjects. After treatment, this response pattern was significantly diminished (P相似文献   

Pharmacokinetics and tolerability of rizatriptan in pediatric migraineurs in a randomized study

Objective.— To evaluate the pharmacokinetic profile and tolerability of single doses of rizatriptan oral disintegrating tablets (ODTs) in pediatric migraineurs. Background.— Acute migraine treatment options for children are limited despite a rising migraine prevalence. No triptans are approved in those under 12, and only sumatriptan nasal spray (European Union) and almotriptan tablets (USA) are approved for those aged 12‐17. Appropriate dose selection based on body weight may be a factor in establishing treatment efficacy in this population. Methods.— Randomized, double‐blind, placebo‐controlled, parallel group, single‐dose study in 6‐ to 17‐year‐old migraineurs. The study was performed between acute migraine attacks. Subjects were allocated to 1 of 2 groups based on body weight: (1) those weighing <40 kg received rizatriptan ODT 5 mg or placebo; (2) those weighing ≥40 kg received rizatriptan 10 mg ODT or placebo. Pharmacokinetic data were compared with historical data on rizatriptan ODT 10 mg in healthy adults. Results.— The geometric mean area under the plasma concentration‐time curve from time 0 to infinity (AUC_(0‐∞)) (hours·ng/mL) and maximum peak plasma concentration (C_max) (ng/mL) were 56.68 (95% confidence interval [CI]: 48.60, 66.09) and 22.39 (95% CI: 17.90, 28.02), respectively, for the <40 kg group and 78.49 (95% CI: 68.93, 89.38) and 22.27 (95% CI: 18.43, 26.92), respectively, for the ≥40 kg group. For the comparison of children vs adults, the geometric mean ratios for rizatriptan AUC_(0‐∞) and C_max were 0.85 (90% CI: 0.73, 0.98) and 1.07 (90% CI: 0.86, 1.34), respectively, for the <40 kg group vs historical adult data and 1.17 (90% CI: 1.02, 1.34) and 1.06 (90% CI: 0.87, 1.30), respectively, for the ≥40 kg group vs historical adult data. There were no serious adverse events, and rizatriptan was generally well tolerated. Conclusions.— In pediatric migraineurs, a weight‐based dosing scheme generated plasma rizatriptan AUC_(0‐∞) and C_max values that were generally similar to those historically observed in adults administered a 10‐mg dose of rizatriptan ODT (a proven effective dose). The data support further evaluation of the safety, tolerability, and efficacy of this rizatriptan dosing scheme in larger scale clinical trials in the pediatric migraineur population.     

An azoospermic male with a novel chromosome 46, XX,der(15)t(Y; 15)(p11.3; p12)

Male individuals with a 46, XX karyotype are commonly diagnosed with 46, XX male sex reversal syndrome, one of the rarest sex chromosomal anomalies. In this case, we report a rare XX male with Y‐specific DNA sequences located near the end of chromosome 15 p‐arm, which was verified by fluorescent in situ hybridization (FISH) as well as copy number variation sequencing (CNV‐seq) based on the next‐ generation sequencing method (>100 Kb). To the best of our knowledge, there have been no reports of XX male with the Yp region transferred to the terminal of chromosome 15 short arm.     

Electrochemical characterization of and theoretical insight into a series of 2D MOFs, [M(bipy)(C4O4)(H2O)2]·3H2O (M = Mn (1), Fe (2), Co (3) and Zn (4)), for chemical sensing applications

The electrochemical sensing applications of a series of water-stable 2D metal–organic framework (MOF)-modified screen-printed carbon electrodes (SPCEs) are reported. The MOF materials in this study are [M(bipy)(C₄O₄)(H₂O)₂]·3H₂O, in which bipy = 4,4′-bipyridine and M = Mn, Fe, Co and Zn. The MOF materials are characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM), showing that the MOFs have a layer-by-layer rod structure with a smooth surface. We use the nitrofurazone molecule as a probe to investigate the influence of the metal ions of MOFs on electrochemical sensing ability. Cyclic voltammetry demonstrated that the Mn-MOF electrode of interest delivered stronger signals than that of other electrodes. Through first-principles calculations, we also revealed that the change in the spin polarization of divalent metal ions passing from the free ion state to the MOF environment appeared to be significantly correlated with the enhancement in the peak response current. The theoretical and experimental results consistently indicate that Mn-MOF has the smallest bandgap and good sensitivity among these MOF materials. Accordingly, we proposed a simple model to illustrate this observation and disclosed the importance of the electron configuration of the transition metal constructing the MOF materials used in improving electrochemical sensing applications.

Framework-to-metal charge transfer of the MOF materials results in enhancing electrochemical sensing ability to nitrofurazone.     

The (CF3C(O)NH)(C6H5CH2NH)2P(O) phosphoric triamide as a novel carrier with excellent efficiency for Cu(ii) in a liquid membrane transport system

Transport of Ag(i), Cd(ii), Co(ii), Cu(ii), Ni(ii), Pb(ii) and Zn(ii) cations across a bulk liquid membrane (BLM) containing N,N′-dibenzyl-N′′-(2,2,2-trifluoroacetyl)-phosphoric triamide (PTC) as a new carrier is studied by atomic absorption spectrometry. The results show selective and efficient transport of the copper(ii) cation from aqueous solution in the presence of the other cations. Various factors are optimized in order to obtain maximum transport efficiency. The PTC ligand is characterized by single crystal X-ray diffraction analysis, IR, NMR (¹⁹F, ³¹P, ¹H, ¹³C) and mass spectroscopy. The complex formation reaction between copper(ii) and PTC is studied by a conductometric method, which shows the 1 : 1 stoichiometry for ligand and copper(ii).

Selective transport of Cu(ii) cation in the presence of six other cations across a bulk liquid membrane containing a novel phosphoric triamide carrier is studied.     

Higher variability of phosphene thresholds in migraineurs than in controls: a consecutive transcranial magnetic stimulation study

The aim of this study was to characterize the temporal course of phosphene thresholds (PT) using transcranial magnetic stimulation (TMS) in control subjects and in subjects with migraine and to observe whether changes in PT over time can predict a subsequent migraine attack. PTs were measured in 16 migraineurs [nine with aura (MA) and seven without aura (MoA)] and nine controls five times over an approximately 10-week period. Mean PTs were not significantly different between migraineurs and controls; however, there was a trend in MA showing lower thresholds. The minimum threshold values were also smaller in MA subjects than in MoA or control subjects. Generally, PTs had higher variance in migraineurs than in controls, revealing a significant increase in standard deviation of PTs in MA subjects. There was no significant difference of thresholds from the first to the last stimulation in controls and in MoA subjects, but the 3rd, 4th and 5th measurements of MA subjects were significantly lower than their first measurements. Four migraineurs experienced headache within 1 day after one of the measurements. They had either very low or very high PTs compared with the PT values which were not followed by a migraine attack. Our results imply that migraineurs show a higher variability among PT measurements over time than controls, revealing unstable excitability levels in these patients. Additionally, both particularly high and low PTs might predict a subsequent headache in some individuals.     

Sumatriptan nasal spray in adolescent migraineurs: a randomized, double-blind, placebo-controlled, acute study

OBJECTIVE: To compare the efficacy and tolerability of sumatriptan nasal spray (NS) (5, 20 mg) versus placebo in the acute treatment of migraine in adolescent subjects. BACKGROUND: Currently, no triptan is approved in the United States for the treatment of migraine in adolescent subjects (12 to 17 years). In a previous randomized, placebo-controlled study of 510 adolescent subjects, sumatriptan NS at 5, 10, and 20 mg doses was well tolerated. However, the primary efficacy analysis for headache relief with 20 mg at 2 hours did not demonstrate statistical significance (P = .059). A second study was initiated to evaluate the efficacy of sumatriptan NS in this population. METHODS: This was a randomized (1:1:1), placebo-controlled, double-blind, parallel-group study. Overall, 738 adolescent subjects (mean age: 14 years) with > or = 6-month history of migraine (with or without aura) self-treated a single attack of moderate or severe migraine. The primary endpoints were headache relief at 1 hour and sustained relief from 1 to 24 hours. Pain-free rates, presence/absence of associated symptoms, headache recurrence, and use of rescue medications were also assessed. Tolerability was based on adverse events (AEs) and vital signs. RESULTS: Sumatriptan NS 20 mg provided greater headache relief than placebo at 30 minutes (42% vs. 33%, respectively; P = .046) and 2 hours (68% vs. 58%; P = .025) postdose, but did not reach statistical significance at 1 hour (61% vs. 52%; P = .087) or for sustained headache relief from 1 to 24 hours (P = .061). Significant differences (P < .05) in favor of sumatriptan NS 20 mg over placebo were observed for several secondary efficacy endpoints including sustained relief from 2 to 24 hours. In general, sumatriptan NS 5 mg percentages were slightly higher than placebo but the differences did not reach statistical significance. Both doses of sumatriptan NS were well tolerated. No AEs were serious or led to study withdrawal. The most common event was taste disturbance (2%, placebo; 19%, sumatriptan NS 5 mg; 25%, sumatriptan NS 20 mg). CONCLUSIONS: This study suggests that sumatriptan may be beneficial to some adolescents and is generally well tolerated in the acute treatment of migraine in this population.     

Adsorption and dissociation behavior of H2 on PuH2 (100), (110) and (111) surfaces: a density functional theory+U study

The density functional theory (DFT) and DFT plus correction for on-site Coulomb interaction (DFT+U) method were performed to investigate the adsorption and dissociation of H₂ on PuH₂ (100), (110) and (111) surfaces. Overall, the H₂ molecule can be adsorbed on the PuH₂ surface without spontaneous dissociation. The calculated H–H bond lengths (R_H–H) are all elongated to different degrees, and the R_H–H at different adsorption sites is about 0.84–4.21% longer than in the gas phase. We found that the dissociation of H₂ on the (110) surface is a spontaneous exothermic process, and a total energy of 0.60 eV is released in the whole process. The smaller barriers corroborate that the migration of an H atom on the PuH₂ surface is possible, and even spontaneous diffusion may occur. The spontaneous migration of a hydrogen atom adsorbed on the (110) surface from the surface to the interior promotes the conversion of PuH₂ to PuH₃, which may be the fundamental driving force of hydrogenation corrosion. Our results provide useful information to explain the mechanism of hydrogenation corrosion on the PuH₂ surface.

The density functional theory (DFT) and DFT plus correction for on-site Coulomb interaction (DFT+U) method were performed to investigate the adsorption and dissociation of H₂ on PuH₂ (100), (110) and (111) surfaces.     

A neuroendocrinological study in female migraineurs: prolactin and thyroid stimulating hormone responses

To evaluate the change of the neurotransmitter function in migraine, a neuroendocrinological study was performed in eleven female migraineurs and nine female controls. Thyrotropin releasing hormone, luteinizing hormone releasing hormone, and insulin were simultaneously loaded (the Triple test). Before and after loading, serum glucose, prolactin (PRL), thyroid stimulating hormone (TSH), luteinizing hormone, follicle stimulating hormone, adrenocorticotropic hormone, cortisol, human growth hormone and beta-endorphin were measured. The Triple test produced an increase of PRL in both migraine and control groups, but in migraineurs the increase was significantly larger than in controls. TSH also increased in response to the test, but the TSH response in patients was less than in controls, although not significantly so. The responses of other substances showed no significant differences between the two groups. Although dopaminergic hypofunction in migraine has been proposed by some authors, the present findings rather suggest a serotonergic hyperfunction.     

Warfarin hypersensitivity due to gluten-sensitive enteropathy: a case study

A 53 year old female who was maintained on long-term warfarin therapy due to history of pulmonary embolism, repeatedly presents with an abnormally prolonged Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT). After many asymptomatic episodes were corrected with Vitamin K therapy to temporarily reverse the effects of the warfarin, the cause of the apparent coagulopathy was further investigated. Factor Activity Assays of the common pathway factors II, IX, and X all revealed critically low values; below the threshold even a loading dose of warfarin is typically capable of eliciting. The patient tested strongly positive for Tissue Transglutaminase IgA, which is highly suggestive of a gluten-sensitive enteropathy. One effect of this condition is malabsorption due to flattened intestinal villi. The patient was determined to have an acquired vitamin K deficiency secondary to gluten-sensitive enteropathy. Her condition was exacerbated by the long-term warfarin therapy, resulting in the prolonged PT and PTT. The patient was treated with vitamin K therapy, which reversed the deficiency and corrected her abnormal coagulation results.