MA Patients Research Articles

Calcitonin gene-related peptide triggers migraine-like attacks in patients with migraine with aura

Calcitonin gene-related peptide (CGRP) is a key molecule in migraine pathogenesis. Intravenous CGRP infusion triggers delayed migraine-like attacks in patients with migraine without aura (MO). In contrast to patients with MO, in prior studies patients with familial hemiplegic migraine (FHM) did not report more migraine-like attacks compared to controls. Whether CGRP triggers migraine in patients with typical (non-hemiplegic) migraine with aura is (MA) unknown. In the present study we examined the migraine inducing effect of CGRP infusion in patients suffering from MA and healthy controls. Fourteen patients suffering exclusively from migraine with typical aura (MA) and 11 healthy volunteers received a continuous intravenous infusion of 1.5 µg/min CGRP over 20 minutes. Headache and other migraine symptoms were scored every 10 minutes for one hour and self recorded hourly thereafter and until 13 hours post-infusion. CGRP infusion induced significantly more delayed headaches in MA patients (12 out of 14) than in controls (2 out of 11) (p = 0.001). Furthermore, significantly more MA patients (57%; 8 out of 14) fulfilled criteria for an experimentally induced migraine attack after CGRP than controls (0%; 0 out of 11) (P = 0.003). Four patients (28%) reported aura symptoms after CGRP infusion. CGRP triggered migraine-like attacks without aura in patients suffering exclusively from MA. It also triggered a typical aura in 28% of the patients. These data indicate similar neurobiological pathways responsible for triggering migraine headache in MA and MO patients, and suggest differences between MA/MO and FHM.

The Relationship Between Homocysteine and Genes of Folate‐Related Enzymes in Migraine Patients

It has been suggested that homocysteine (Hcy) and the 5'-10'-methylenetetrahydrofolate reductase (MTHFR) C677T variant are implicated in the pathogenesis of migraine. Homocysteine has the potential to damage endothelium and accelerate atherosclerosis. Genetic factors such as the MTHFR C677T polymorphism, and other polymorphisms in folate-related genes associated with high homocysteine levels, may contribute to increasing this vascular risk. We recruited 427 migraine patients (199 without aura [MO]; 228 with aura [MA]), and 310 controls in a neurologic clinic. Hcy levels and 6 polymorphisms corresponding to 6 folate-related genes, including the MTHFR C677T variant, were determined in all migraine participants and in a subset of 155 controls. We found higher sex-adjusted Hcy levels in MA (mean: 11.02 microM) than MO patients (9.86 microM; P = .005 for the difference). Hcy levels higher than 12.0 microM doubled the risk for MA (OR = 2.145; 95% confidence intervals [CI] = 1.3-3.4; P = .001), and those higher than 15.0 microM incurred a 6-fold increase (OR = 5.95; 95% CI = 2.1-20.0, P < .001). The number of MTHFR 677T alleles was the best genetic predictor of Hcy levels (r(2) = 0.06; P = 6.2e-6; corrected for genetic variants analyzed) and this effect remained significant after correction for other confounding factors. Using multi-dimensionality reduction approaches, we observed significant epigenetic interaction among some of the folate-related genetic variants to predict higher Hcy levels, and also among higher Hcy levels and folate-related genetic variants to predict the end-diagnosis of MA only among migraineurs. In controls, Hcy levels and the number of MTHFR 677T alleles were found to be intermediate between those observed in MA and MO patients. Our results suggest that MA patients have higher Hcy levels. We also observed complex epigenetic interaction among folate-related enzymes, sex, and Hcy levels predicting MA phenotype. Nevertheless, genetic factors explained only a minor proportion of the variance for both Hcy plasma levels and for predicting MA phenotype. Determination of MTHFR C677T polymorphisms and Hcy levels may be useful to identify patients with a high risk of suffering from MA.

Examination of TIMP-1 Levels and Relapse-Free Survival for Patients in NCIC CTG MA.14 Who Received Adjuvant Tamoxifen +/- Octreotide LAR.

Abstract Background: Tissue inhibitor of metalloproteinase-1 (TIMP-1) has been shown to have diverse multifunctional roles in tumorigenesis. AL/KL/SA postulated from first line metastatic endocrine therapy that elevated pre-treatment serum TIMP-1 required additional therapy. NCIC CTG MA.14 adjuvant endocrine trial permitted examination of whether TIMP-1 serum levels post-chemotherapy was associated with RFS. Methods: NCIC CTG MA.14 is a trial where 667 postmenopausal patients were randomized to receive adjuvant tamoxifen +/- octreotide LAR with a stratification factor of no, concurrent or sequential chemotherapy. For the purposes of this work, this was simplified to whether a patient had or had not received adjuvant chemotherapy prior to the serum draw. Serum TIMP-1 was assessed on &amp;gt;90% of the trial patients. We examined the effect of baseline TIMP-1 levels on relapse-free survival (RFS) of 1) all types, 2) bone only, 3) all types of bone, and 4) non-bone, by timing of chemotherapy before the serum draw utilizing continuous TIMP (ng/ml) and categorical TIMP (&amp;lt;454, &amp;gt;454 ng/ml, based on 95% non-parametric cut-point for healthy post-menopausal females). Data were available on patient and tumour characteristics of age (years), pathologic tumour size (cm), pathologic lymph node status (# nodes), IGF-1, C-peptide, IGFBP-3. Step-wise forward Cox multivariate models were used where a factor was added if p&amp;lt;=0.05, and interaction terms were added for TIMP-1 level and timing of chemotherapy. Results: High (categorical) TIMP-1 was significantly associated with longer RFS (p=0.04) in the non-bone RFS multivariate model in the subgroup of patients who had prior chemotherapy, but not in those who did not. The interaction between TIMP-1 and administration of chemotherapy before serum draw was significant (p=0.02). High (continuous) TIMP-1 was significantly associated with longer bone only RFS (p=0.04) in subgroup who had no chemotherapy before the serum draw, but not in those who may or may not have had it after. There was no significant interaction effect. Categorical and continuous TIMP-1 were not associated with any other type of RFS. Conclusions: We found a predictive benefit with the assessment of serum TIMP-1 in hormone receptor positive patients, that high TIMP-1 levels after adjuvant chemotherapy were predictive of a reduction in non-bone RFS. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3022.

Predictors of Engagement in a Coping and Communication Support Intervention for Older Patients with Advanced Cancer

To examine patterns and predictors of engagement in a coping and communication support (CCS) intervention tailored to the preferences of middle-aged and older patients in the early treatment phase for late-stage cancer. Randomized controlled trial examining processes and outcomes of a CCS intervention for patients with late-stage cancer over time. Two ambulatory cancer clinics providing care for underserved populations in Cleveland. One hundred nine middle-aged (MA: aged 40-60) and 101 young-old (YO: aged 61-80) patients randomized to the CCS intervention, surviving to 3 months after enrollment and averaging 2 months of 24/7 access to the intervention. Engagement was assessed in the average number of patient-CCS practitioner (CCSP) contacts per month during the initial 2 months of access to the intervention. Baseline data from patient interviews and chart reviews were used to test a model of prediction. MA patients averaged more patient-CCSP contacts per month than YO patients (mean 2.6 +/- 2.5 vs 2.0 +/- 1.2, P=.02), although both age groups were engaged. African-American patients (P=.007) and those with a higher blunting style (P<.01), reporting more family discord in cancer communication (P=.009), and receiving fewer active cancer treatments (P=.008) were more engaged in the CCS intervention in the initial months. Psychooncology interventions individualized to patient preferences can effectively reach older and underserved populations. Such interventions may be especially important to patients using more avoidant behaviors, experiencing more family discord communicating about cancer, or receiving fewer aggressive treatments in the early treatment phase for late-stage cancer.

Hematopoietic Cell Transplantation for Chronic Lymphocytic Leukemia: Similar Efficacy of Non-Myeloablative and Myeloablative Conditioning; Long-Term Evaluation From the University of Minnesota.

Abstract 3385Poster Board III-273Allogeneic hematopoietic cell transplantation (HCT) for chronic lymphocytic leukemia (CLL) is increasingly utilized. We retrospectively analyzed outcomes of HCT for 43 patients with CLL at the University of Minnesota from February 1985 through March 2009 using myeloablative (MA, n=19) (total body irradiation [TBI] 1320 cGY in 8 fractions and cyclophosphamide [Cy] 60 mg/kg x 2 days) and non-myeloablative (NMA, n=24) preparative regimens (fludarabine 40 mg/m2 × 5 days or cladribine 50 mg/m2 IV with TBI 200cGy in 1 fraction and either oral busulfan [Bu] 8 mg/kg divided every 6 hours over 2 days or Cy 50 mg/kg x1 day). Graft-versus-host disease (GVHD) prophylaxis included cyclosporine (CSA) and methotrexate in most MA patients and CSA and mycophenolate mofetil (MMF) for all NMA patients. Median follow up for survivors was 3.3 years. Nine-two percent of NMA HCT took place after 2000 whereas only 26% of MA HCTs happened during this time. Most patients were male (15/19 MA, 20/24 NMA). Time from diagnosis to treatment was nearly twice as long in NMA vs. MA patients (median 72 vs. 39 months) with MA patients progressing through a median of 3 regimens (range, 1-5) and NMA 4 (1-7). Poor-risk cytogenetics (11q-, 17p-) were found in 5 MA and 10 NMA patients. Seven and 13 patients were fludarabine refractory in the MA and NMA groups, respectively. Eighteen patients in the MA group had matched related donors (MRD), while only 10 MRD were amongst the NMA patients. Umbilical cord blood stem cells were used in 12 NMA patients. Neutrophil recovery was slightly faster after NMA HCT vs. MA (median 12.5 vs. 18.5 days; p=0.14). Incidence of acute GVHD, grades II-IV, was similar (p=0.11) but grades III-IV at day 100 was more frequent in the NMA than the MA group (33% vs. 5%, p=0.04). The chronic GVHD incidence was 43% (95% CI, 18-68%) in MA and 29% in NMA (11-47%, p=0.08) patients. Transplant-related mortality (TRM) at 1 year was 42% (20-64) in the MA arm vs. 25% (8-42) (p=0.34) for the NMA group. Relapse rates at 3 years were higher in the NMA HCT group (MA 18% [0-36] vs. NMA 26% [8-44]). Three-year progression-free survival (PFS) was similar in MA (33% [13-55]) and NMA (39% [19-58]) patients (p=0.61). Overall survival at three years was also similar (MA 37%, [15-60] vs. NMA 52%, [30-70]) (p=0.28). While these data suggest that dose intensity may affect TRM and relapse, NMA HCT yields equivalent and encouraging PFS and OS as compared to MA HCT. Our results support further investigation of the role of allogeneic transplantation in the treatment of high risk and advanced CLL. Disclosures:No relevant conflicts of interest to declare.

Comparison of Outcomes Between 2-Year Survivors After Myeloablative and Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation.

Abstract 3307Poster Board III-195Myeloablative (MA) and reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (alloHSCT) are both effective treatment approaches for patients with otherwise incurable hematologic diseases. However, patients who survive beyond 2 years are still at risk for significant morbidity and mortality. Differences in these later post-transplant outcomes may exist between those patients who received MA and RIC regimens. We therefore investigated outcomes on 677 patients (590 MA and 87 RIC) with hematologic diseases who underwent alloHSCT at our institution from 1/90-12/06. 235 MA and 37 RIC patients survived >2 years (40% vs. 42%, respectively, p=0.63). Factors predictive for surviving >2 years on multivariable analysis included younger age, greater Karnofsky performance status (KPS) at transplant, related donor and HLA matched donor. For > 2 yrs survivors, as compared to those treated with MA conditioning the RIC patients were older (median age 55 vs. 39 yrs, p<0.001), had better KPS at transplant (p<0.001), more commonly had lymphoid diagnoses (24 [65%] vs. 62[28%], p<0.001), had longer median time from diagnosis to transplant (19 vs. 6 mos, p<0.001), had more prior chemotherapy (p<0.001) and radiation therapy (p=0.036), more often received a TBI-based preparative regimen (100% vs. 15%, p<0.001) and peripheral blood stem cells (100% vs. 5%, p<0.001). There were no differences between the groups regarding gender, race, comorbidity index score, donor relationship, donor to recipient gender, HLA matched transplants, incidence or severity of acute or chronic GVHD, CMV infection, other infections or overall survival. Disease relapse was higher in the RIC group (6[16%] vs. 22[9%], p=0.048). Currently, for these >2 yr survivors 178 (76%) MA and 28 (76%) RIC patients remain alive at median follow-ups of 72 (range, 3-196) vs. 33 mos (range, 5-86), respectively (p<0.001). Death occurred most commonly for the MA pts due to relapse, then chronic GVHD, pulmonary toxicity, infection and secondary malignancy, while relapse and secondary malignancy were the most common causes for RIC pts. As compared to those with lymphoid diseases those with myeloid diseases had superior relapse-free survival (RFS) (Figure, p=0.012) and tended to have better overall survival (OS) (p=0.09). [Display omitted] Myeloid disease status was also predictive of lower disease relapse (p=0.005) and better relapse-free survival (p=0.014) on multivariable analysis. However, no differences in CMV infection, other infections, incidence and severity of chronic GVHD, relapse, RFS or OS were found when comparing MA vs. RIC patients for myeloid and lymphoid diseases independently. We conclude that the majority of MA and RIC patients surviving >2yrs after alloHSCT remain alive and relapse-free. The superior RFS for patients with myeloid diseases is likely related to a more robust graft-vs-malignancy effect. Further strategies with novel approaches to decrease late relapses for these patients are warranted. DisclosuresNo relevant conflicts of interest to declare.

Differences in short-term primary motor cortex synaptic potentiation as assessed by repetitive transcranial magnetic stimulation in migraine patients with and without aura

To find out more about glutamatergic and gabaergic transmission in migraine, in this study we investigated glutamate-dependent short-term synaptic potentiation and GABA-dependent inhibitory cortical interneuron excitability as assessed by 5 Hz-rTMS delivered over primary motor cortex (M1) (motor evoked potential, MEP, amplitude facilitation and cortical silent period, CSP, duration lengthening) in migraine patients with (MA) and without aura (MwoA) and healthy controls. We studied 37 patients with migraine (19 MA and 18 MwoA) and 19 healthy control subjects. 5 Hz-rTMS was delivered at 120% resting motor threshold to the hand motor area of the left hemisphere with the target muscle at rest and during contraction. Three of the MA patients were also tested at the end of visual aura during a spontaneous migraine attack. ANOVA showed that the MEP significantly increased in size and CSP significantly lengthened during 5 Hz-rTMS in the three groups tested. The 5 Hz-rTMS-induced MEP facilitation differed significantly being highest in MA patients. In the three patients tested both ictally and interictally the MEP increased during the interictal session but remained unchanged when the visual aura ended. Our study shows that the neurophysiological feature that differentiates MA patients from MwoA patients and healthy controls is an abnormal M1 susceptibility to 5 Hz-rTMS both outside and during the attack suggesting that glutamate-dependent short-term M1 cortical potentiation patterns differ in migraine with and without aura.

Migraines with and without aura and their response to preventive therapy with topiramate

Data from the Prolonged Migraine Prevention (PROMPT) with Topiramate trial were evaluated post hoc to determine whether topiramate could prevent migraine auras, and whether its efficacy in preventing migraine headaches was similar in patients with (MA; n = 269) and without (MoA; n = 542) aura. Migraines and auras were recorded during prospective baseline, 6-month open-label (OL) topiramate and 6-month double-blind (DB), placebo-controlled phases. In the last 28 OL days, migraines without aura and migraine auras decreased by 43.1% and 54.1%, respectively, in MA patients. MoA patients experienced a 44.3% reduction in migraines. In the DB phase, increases in migraines with placebo vs. topiramate were similar to the full study, but were generally not statistically significant, probably due to lack of power in the subgroup analysis. Similarly, there were no statistically significant changes in number of auras between groups. Thus, topiramate appears to reduce migraine auras in parallel with headache reductions, which are similar in patients with and without aura.

Different circulating metalloproteinases profiles in women with migraine with and without aura

Background We compared the circulating levels of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitors of metalloproteinase (TIMP)-1, TIMP-2, and MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios in migraine patients without aura (MWA) and in migraine patients with aura (MA) with those found in healthy subjects (controls). Methods We studied 80 migraine (40 MWA and 40 MA) women and 40 controls. Pro-MMP-2 levels were determined by zymography and MMP-9, TIMP-1, and TIMP-2 levels were determined by ELISA. Results While we found similar TIMP-2 levels, higher plasma pro-MMP-2 and pro-MMP-2/TIMP-2 ratios were found in MWA and MA patients compared with controls ( P < 0.05). Higher TIMP-1 levels and lower MMP-9/TIMP-1 ratios were found in MA, but not in MWA, patients compared with controls ( P < 0.05). We found no significant differences when patients without headache attack were compared with patients having a headache attack (all P < 0.05). Conclusions We showed an increased net MMP-2 activity in MWA and MA. The increased MMP-9/TIMP-1 ratios in MWA patients contrast with the lower MMP-9/TIMP-1 ratios in MA patients and may reflect pathophysiological differences between these conditions.

Clinical analysis on 13 cases of adult macrophage activition syndrome

Objective To evaluate clinical feature of adult Macrophage Activition Syndrome in order to improve our recognition of it. Methods Clinical data of 13 patients with Macrophage Activition Syndrome were analyzed. Results Fever, arthritis, splenomegaly, jaundice and hepatomegaly were the most common symptoms or signs seen in adult MAS patients. Increased liver enzymes, hyperferritinemia, hypocytosis, hypertriglyceridemia and abnormal coagulation were the most common abnormal laboratory examination. Average ferritin level of the patients was 10237 μg/L. All patients received glucocorticosteroid. 7 patients received additional immune sup-pression treatment. 5 patients died, and 8 patients got remission (2 patiens relapsed in the course of disease). Conclusion Adult Macrophage Activition Syndrome is a life-threatening complication of rheumatic disease and has no typical symptom at onset. When there axe unexplained high fever, hypoeytosis, hyperferritinemia and hy-pertriglyceridemia in rheumatic disease, we should take bone marrow examination to diagnosis the disease as soon as possible. Key words: Adult macrophage activition syndrome; Rheumatoid diseases

Role of the ACE ID and MTHFR C677T polymorphisms in genetic susceptibility of migraine in a north Indian population

Migraine is a common debilitating neurovascular disorder. The vascular genes ACE and MTHFR are involved in alterations in vascular endothelium and are suggested to play a role in migraine susceptibility. The aim of our study was to find out the role of ACE ID (rs no. 4646994) and MTHFR C677T (rs no.1801133) polymorphisms in genetic susceptibility of migraine in north Indian population. A total of 150 migraine patients, 220 non-migraine headache patients (Disease controls) and 150 age–sex matched normotensive healthy controls were enrolled for our study. DNA was isolated from peripheral blood leucocytes, and subjected to amplification using specific primers and genotyped using PCR (in case of ACE ID) or PCR-RFLP (in case of MTHFR C677T) methods. χ2 test was applied for the analysis of genotypic and allelic distributions. Logistic regression analysis was used to find out contribution of genetic polymorphisms to the risk of disease. ACE DD genotype showed significant association in migraine patients with aura (MA) but a marginal significance in female MA patients in comparison with healthy controls. No significant differences in genotype and allelic frequencies of MTHFR C677T polymorphism were found on comparing migraine patients with either disease controls or healthy controls. In contrast, we found synergistic role of ACE (DD)⁎MTHFR (CT) interaction, showing a positive association in total migraine with aura patients as well as female migraine patients with aura when compared with healthy controls.

Selective Diffusion Changes of The Visual Pathways in Patients with Migraine: A 3-T Tractography Study

Using diffusion tensor (DT) tractography, we quantified optic radiation (OR) structural changes in seven migraine patients with (MA) and eight without visual aura (MoA) and their relation to clinical manifestations and T2-visible burden. The corticospinal tract and the corpus callosum were studied as 'control' white matter (WM). No difference was found for any of the WM fibre bundles metrics between controls and MoA patients. MA patients had reduced average fractional anisotropy (FA) of both OR compared with controls and reduced average FA of the right OR compared with MoA patients. They also showed higher right OR mean diffusivity than controls. OR metrics were not correlated with clinical and magnetic resonance imaging (MRI) metrics. DT tractography reveals OR changes in MA patients that might represent a phenotypic biomarker of the disease given the lack of correlation with clinical and structural MRI metrics.

Decreased number and function of endothelial progenitor cells in patients with migraine

Migraine carries an increased risk for cardiovascular and cerebrovascular diseases that cannot be explained by traditional cardiovascular risk factors. The circulating endothelial progenitor cell (EPC) number is a surrogate biologic marker of vascular function, and diminished EPC counts are associated with higher cardiovascular risk. We investigated whether abnormalities in EPC levels and functions are present in migraine patients. Consecutive headache patients (n =166) were enrolled, including those with tension type headache (TTH; n = 74), migraine without aura (MO; n = 67), and migraine with aura (MA; n = 25). EPC colony-forming units in peripheral blood samples and migratory capacity to chemoattractants (stromal cell-derived factor 1 and vascular endothelial growth factor) and cellular senescence levels were assayed in risk factor-matched subjects (n = 6 per group). The TTH group had more cardiovascular risk factors, more headache days, and higher Framingham risk scores than the other two groups. Mean numbers of EPC colony-forming units were 47.8 +/- 24.3 in TTH, 20.4 +/-22.2 in MO, and 8.6 +/- 10.1 in MA patients (p < 0.001 in TTH vs MO; p = 0.001 in MO vs MA). EPC colony counts of normal subjects (n = 37) were not significantly different from those with TTH. Multiple linear regression models identified only MO, MA, and the presence of migraine (MO + MA) as significant predictors of EPC levels. In addition, EPCs from migraine patients (MO and MA) showed reduced migratory capacity and increased cellular senescence compared with EPCs from TTH or normal subjects. Circulating endothelial progenitor cell (EPC) numbers and functions are reduced in migraine patients, suggesting that EPCs can be an underlying link between migraine and cardiovascular risk.

Visual evoked potential latency, amplitude and habituation in migraine: A longitudinal study

Objective It has not been previously studied with a paired longitudinal design if visual excitability changes occur in the preattack period across the migraine cycle, or how excitability and habituation relate to migraine-attack severity, clinical photophobia and serotonin metabolism. Methods Monocular 62′ check reversals were applied in 33 adult migraine patients without aura (MwoA), 8 with aura (MA) and 31 controls. VEP was recorded in four blocks of 50 stimuli. P1 (P100) and N2 (N145) latency and N1P1 and P1N2 amplitude were measured. Serotonin was measured in plasma and platelets sampled before each session. Sessions were classified as preattack, attack, postattack or interictal. Results Migraine patients had significantly higher P1N2 amplitude before the attack compared to a paired interictal recording ( n = 13, p = 0.03), but habituation difference was not found. MA patients had significantly higher P1N2 and N1P1 amplitude than controls and MwoA. P1 latency correlated positively with headache history duration. During attack, a positive correlation between P1N2 amplitude habituation and serotonin emerged in MA patients. Conclusions Increased VEP P1N2 amplitude was observed within a few days before the attack. Visual cortex excitability seems to be generally increased in MA as compared to MwoA patients and controls. Significance Increased excitability of the visual cortex seems to be detectable in the preattack state, supporting the concept of a cyclic CNS dysfunction in migraine.

Interictal Abnormalities of Gamma Band Activity in Visual Evoked Responses in Migraine: An Indication of Thalamocortical Dysrhythmia?

Between attacks, migraineurs lack habituation in standard visual evoked potentials (VEPs). Visual stimuli also evoke high-frequency oscillations in the gamma band range (GBOs, 20-35 Hz) assumed to be generated both at subcortical (early GBOs) and cortical levels (late GBOs). The consecutive peaks of GBOs were analysed regarding amplitude and habituation in six successive blocks of 100 averaged pattern reversal (PR)-VEPs in healthy volunteers and interictally in migraine with (MA) or without aura patients. Amplitude of the two early GBO components in the first PR-VEP block was significantly increased in MA patients. There was a significant habituation deficit of the late GBO peaks in migraineurs. The increased amplitude of early GBOs could be related to the increased interictal visual discomfort reported by patients. We hypothesize that the hypofunctioning serotonergic pathways may cause, in line with the thalamocortical dysrhythmia theory, a functional disconnection of the thalamus leading to decreased intracortical lateral inhibition, which can induce dishabituation.

Allodynia in different forms of migraine

About 60% of patients complain of cutaneous allodynia during migraine episodes, often in the periorbitary region of the pain side. Pre-clinical studies have shown that the underlying mechanism is sensitisation of primary nociceptors and central trigeminovascular neurons and that patients have a lower pain threshold for mechanical stimulation compared to controls. The objective of this study was to determine the prevalence of allodynia during headache attacks in different forms of migraine. The subjects were 221 outpatients consecutively evaluated in the Headache Center of the L. Sacco Hospital in Milan: 114 had only attacks of migraine without aura (MO), 63 had also attacks with aura (MA) and 44 patients with chronic migraine with and without drug overuse (CM). Presence of head allodynia was investigated by a semistructured interview. Statistical analysis was performed by chi square test with Bonferroni correction for multiple comparisons. Forty-seven out of 114 MO patients (41.2%) complained of allodynia during headache episodes, 41 out of 63 MA patients (65.0%), and 29 out of 44 CM patients (65.9%). A higher frequency of allodynia in MA and CM with respect to MO patients was observed (p<0.01 at chi square test). Allodynia was a common complaint in migraineurs, being present in more than 40% patients of each group. A higher frequency was observed in MA and in CM patients. This observation may suggest that both frequency of attacks and presence of aura episodes may contribute to induce changes in neuronal activation threshold thought to sustain allodynia.

Factors associated with change in walking ability in very elderly patients hospitalized for acute myocardial infarction

Background: The aim of this substudy was to identify the predictors of a lesser ability to walk in very elderly patients with acute myocardial infarction (AMI). Methods: Data from 15 acute care hospitals in the Tokai Acute Myocardial Infarction Study (TAMIS)-II sample were used. This is a prospective study of all patients admitted to the hospitals with the diagnosis of AMI from 2001 to 2003. We abstracted the baseline and procedural characteristics including walking ability from detailed chart reviews. In this substudy, patients aged 75 and over were included. Patients were stratified into two categories: 412 patients whose ability to walk was maintained (MA group) and 30 patients whose ability to walk declined (DA group). Results: The DA patients were more likely to have a lower body mass index (BMI) score and signs of heart failure on presentation (cardiac shock, 56.7% vs 15.5%; Killip class > or = III, 73.3% vs 36.6%; pulmonary edema, 60.0% vs 27.91%). DA group patients were more likely to receive vasopressors, intra-aortic balloon pump, or mechanical ventilation. After controlling for statistically significant predictors of a declined ability to walk, DA group patients were significantly more slender than MA group patients, with an adjusted odds ratio of 0.75 (95% confidence interval, 0.62–0.91). DA group patients had a higher shock or mechanical ventilation rate than MA group patients, but not significantly. Conclusions: Our results suggest that a lower BMI value and severe heart failure are significant predictors of reduced walking ability during hospitalization among very elderly patients with AMI.

Relationship Between Migraine and Patent Foramen Ovale: A Study of 121 Patients with Migraine

Migraine is a common neurological disorder, the origins of which remain unknown. Patent foramen ovale (PFO) is considered to have a role in migraine. The relationship between migraine and patent foramen ovale may be stronger in patients suffering from migraine with aura compared to patients with common migraine. The aim of the study was to evaluate the frequency of PFO in patients with migraine with aura (MA+) and compare it with the prevalence of PFO in migraine patients without aura (MA-), and in a healthy age-matched control group. We investigated PFO association with migraine, considering such factors as: A type of migraine aura, frequency of attacks, familial occurrence, sex and age of patients. Patients.-121 patients: 61 patients suffering from migraine with aura, 60 without aura and 65 normal controls. The group of patients with migraine with aura was divided into subgroups regarding to the type of aura. In order to detect PFO the contrast transcranial Doppler was performed during Valsalva maneuver. The presence of PFO was found in 33/61 (54%) patients with MA(+) compared to 15/60 (25%) without aura and 16/65 (25%) control subjects. The difference between MA(+) patients and MA(-) patients and the difference between MA(+) patients and control group was statistically significant (P < .05). There was no association between type of migraine aura and PFO, as well as we found no association between PFO and frequency of attacks, familial occurrence, sex and age of patients and PFO. Our findings suggest possible association of migraine with aura and PFO. It seems that PFO does not influence the type of aura and frequency of attacks of migraine as well as it is not associated with familial occurrence of migraine.

Gsα Mutations in Fibrous Dysplasia and McCune-Albright Syndrome

Fibrous dysplasia (FD) is a focal bone lesion composed of immature mesenchymal osteoblastic precursor cells. Some FD patients also have hyperpigmented skin lesions (café-au-lait spots), gonadotropin-independent sexual precocity, and/or other endocrine and nonendocrine manifestations (McCune-Albright syndrome [MAS]). MAS results from somatic mutations occurring during early development, resulting in a widespread mosaic of normal and mutant-bearing cells, which predicts that the clinical presentation of each patient is determined by the extent and distribution of abnormal cells. These mutations encode constitutively active forms of G(s)alpha, the ubiquitously expressed G protein alpha-subunit that couples hormone receptors to intracellular cAMP generation. These mutations lead to substitution of amino acid residues that are critical for the intrinsic GTPase activity that is normally required to deactivate the G protein. This leads to prolonged activation of G(s)alpha and its downstream effectors even with minimal receptor activation. This explains why MAS patients have stimulation of multiple peripheral endocrine glands in the absence of circulating stimulatory pituitary hormones and increased skin pigment, which is normally induced by melanocyte-stimulating hormone through G(s)alpha/cAMP. Similar mutations are also present in 40% of pituitary tumors in acromegaly patients and less commonly in other endocrine tumors. FD results from increased cAMP in bone marrow stromal cells, leading to increased proliferation and abnormal differentiation. Parental origin of the mutated allele may also affect the clinical presentation, because G(s)alpha is imprinted and expressed only from the maternal allele in some tissues (e.g., pituitary somatotrophs).

Évaluation de la mémoire des événements publics : apport de la batterie EVE-30 chez 108 témoins, chez 10 patients MCI et 10 patients Alzheimer

Public events memory is a principal historic component of memory for the past. We propose a new form of the French public events battery EVE which has been elaborated in 1994. EVE-30 uses 30 events dated between 1920 and 2004. Each event assesses recall, recognition, questions and dating. New exposure and flash souvenirs can be explored. One hundred and eight controls aged between 20 and 79 years, ten patients with Alzheimer's disease (AD) and ten patients with amnesic mild cognitive impairment (aMCI) were evaluated. Mean percentage of good responses in controls group is good with a scale of 72p.cent. Performances were gradually observed. Recognition was respectively better than recall, than datation and than questions. Statistical analysis with ANOVA showed that an older age and a higher level of education significantly influenced results (p<0.05). MCI patients and MA patients exhibited more impaired performances than controls. MCI and MA patients had similar impairment in recognition and questions (very altered in the two groups). The French public events battery (EVE 30) can be performed in one hour and may be considered as a neuropsychological tool for the evaluation of memory for the historical past in clinical practice.