Can anti-Müllerian hormone be predictive of spontaneous onset of pregnancy in women with unexplained infertility?

The objective of the study was to assess anti-Müllerian hormone's (AMH) role in predicting spontaneous onset of pregnancy. This observational cohort study included 83 women with unexplained infertility and normal or low ovarian reserve. Serum AMH, FSH, LH, 17ß-oestradiol, inhibin B levels were measured and the number of early antral follicles (2-9 mm) was evaluated on days 2-5 of the cycle. Spearman's correlation was used for comparison of strength of correlation. The diagnostic power of AMH in predicting spontaneous pregnancy was evaluated by receiver operating characteristic (ROC) curves. Markers of ovarian reserve in pregnant women and women without pregnancy were similar. In the entire study population, any markers (AMH, FSH, AFC, age), correlated with each other, but no marker was correlated with pregnancy. The area under the ROC curve for AMH reached a value of 0.385 ± 0.07 (0.25-0.52, 95% confidence interval, CI); for FSH 0.415 ± 0.08 (0.25-0.58, 95% CI); for AFC 0.418 ± 0.08 (0.26-0.57, 95% CI), for age 0.496 ± 0.08 (0.34-0.65, 95% CI). The study did not find a predictive role for AMH in predicting spontaneous onset of pregnancy. Even when AMH levels are very low, a spontaneous pregnancy may still occur.

Placebo-controlled comparison of effervescent acetylsalicylic acid, sumatriptan and ibuprofen in the treatment of migraine attacks.

Acetylsalicylic acid (ASA) in combination with metoclopramide has been frequently used in clinical trials in the acute treatment of migraine attacks. Recently the efficacy of a new high buffered formulation of 1000 mg effervescent ASA without metoclopramide compared to placebo has been shown. To further confirm the efficacy of this new formulation in comparison with a triptan and a nonsteroidal anti-inflammatory drug (ibuprofen) a three-fold crossover, double-blind, randomized trial with 312 patients was conducted in Germany, Italy and Spain. Effervescent ASA (1000 mg) was compared to encapsulated sumatriptan (50 mg), ibuprofen (400 mg) and placebo. The percentage of patients with reduction in headache severity from moderate or severe to mild or no pain (primary endpoint) was 52.5% for ASA, 60.2% for ibuprofen, 55.8% for sumatriptan and 30.6% for placebo. All active treatments were superior to placebo (P < 0.0001), whereas active treatments were not statistically different. The number of patients who were pain-free at 2 h was 27.1%, 33.2%, 37.1% and 12.6% for those treated with ASA, ibuprofen, sumatriptan or placebo, respectively. The difference between ASA and sumatriptan was statistically significant (P = 0.025). With respect to other secondary efficacy criteria and accompanying symptoms no statistically significant differences between ASA and ibuprofen or sumatriptan were found. Drug-related adverse events were reported in 4.1%, 5.7%, 6.6% and 4.5% of patients treated with ASA, ibuprofen sumatriptan or placebo. This study showed that 1000 mg effervescent ASA is as effective as 50 mg sumatriptan and 400 mg ibuprofen in the treatment of migraine attacks regarding headache relief from moderate/severe to mild/no pain at 2 h. Regarding pain-free at 2 h sumatriptan was most effective.

Interictal lack of habituation of mismatch negativity in migraine.

The aim was to study mismatch negativity features and habituation during the interictal phase of migraine. In migraine patients, a strong negative correlation has been found between the initial amplitude of long latency auditory-evoked potentials and their amplitude increase during subsequent averaging. We studied 12 outpatients with a diagnosis of migraine without aura recorded in a headache-free interval and 10 gender- and age-matched healthy volunteers not suffering from any recurrent headache. The experiment consisted of two sequential blocks of 2000 stimulations, during which 1800 (90%) recordings for standard tones and 200 (10%) for target tones were selected for averaging. The latency of the N1 component was significantly increased in migraine patients in respect of controls in both the first and second repetitions; the MMN latency was increased in the second repetition. In the control group the MMN amplitude decreased on average by 3.2 +/- 1.4 microV in the second trial, whereas in migraine patients it showed a slight increase of 0.21 +/- 0.11 microV in the second repetition. The MMN latency relieved in the second trial was significantly correlated with the duration of illness in the migraine patients (Spearman correlation coefficient: 0.69; P < 0.05). The increases in N1 latency and MMN latency and amplitude, the latter correlated with duration of illness, seemed to be due to a reduced anticipatory effect of stimulus repetition in migraine patients. This suggests that such hypo-activity of automatic cortical processes, subtending the discrimination of acoustic stimuli, may be a basic abnormality in migraine, developing in the course of the disease.

Reduced habituation to experimental pain in migraine patients: a CO(2) laser evoked potential study.

The habituation to sensory stimuli of different modalities is reduced in migraine patients. However, the habituation to pain has never been evaluated. Our aim was to assess the nociceptive pathway function and the habituation to experimental pain in patients with migraine. Scalp potentials were evoked by CO(2) laser stimulation (laser evoked potentials, LEPs) of the hand and facial skin in 24 patients with migraine without aura (MO), 19 patients with chronic tension-type headache (CTTH), and 28 control subjects (CS). The habituation was studied by measuring the changes of LEP amplitudes across three consecutive repetitions of 30 trials each (the repetitions lasted 5 min and were separated by 5-min intervals). The slope of the regression line between LEP amplitude and number of repetitions was taken as an index of habituation. The LEPs consisted of middle-latency, low-amplitude responses (N1, contralateral temporal region, and P1, frontal region) followed by a late, high-amplitude, negative-positive complex (N2/P2, vertex). The latency and amplitude of these responses were similar in both patients and controls. While CS and CTTH patients showed a significant habituation of the N2/P2 response, in MO patients this LEP component did not develop any habituation at all after face stimulation and showed a significantly lower habituation than in CS after hand stimulation. The habituation index of the vertex N2/P2 complex exceeded the normal limits in 13 out of the 24 MO patients and in none of the 19 CTTH patients (P<0.0001; Fisher's exact test). Moreover, while the N1-P1 amplitude showed a significant habituation in CS after hand stimulation, it did not change across repetitions in MO patients. In conclusion, no functional impairment of the nociceptive pathways, including the trigeminal pathways, was found in either MO or CTTH patients. But patients with migraine had a reduced habituation, which probably reflects an abnormal excitability of the cortical areas involved in pain processing.

Nociceptive temporalis inhibitory reflexes evoked by CO2-laser stimulation in tension-type headache.

The aim of the study was to evaluate the laser-induced suppression periods of the temporalis muscle in patients with tension-type headache, compared with the pattern of temporalis activity suppression induced by electrical stimulation. Fifteen patients with chronic and 10 with episodic tension-type headaches were selected. Suppression periods were recorded simultaneously from both temporalis muscles using both electrical stimuli and CO2-laser stimuli. A significant reduction in the later electrically induced suppression period was found in both tension-type headache groups. Laser stimulation induced a first suppression period (LSP1) with a latency of about 50 ms in all patients. The features of LSP1 were similar across groups. The LSP1 should correspond to the first suppression period induced by electrical stimulus, which is partly a nociceptive response, whereas the second period seemed negligibly linked with the activation of pain-related afferents, though probably their activation may contribute to increase the reflex duration and to emphasize abnormalities in tension-type headache.

Features of the blink reflex in individuals at risk for Huntington's disease.

The aim of the study was to correlate the features of the blink reflex (BR) with the genetic abnormalities and the clinical findings in patients with Huntington's disease (HD) and asymptomatic gene carriers. Twenty patients with HD and 20 relatives were studied. Mutation analysis was performed for the CAG expansion within the HD gene using HD 333-HD 447 as oligonucleotide primers. The BR was elicited transcutaneously by electrical stimulation of the right supraorbital nerve. The recovery curve of the R2 and R3 responses after a conditioning stimulus was evaluated. R2 latency and duration and R3 duration were significantly increased in HD patients and in presymptomatic carriers in comparison with controls; reduced R2 recovery was also clear in both HD and gene-carrier relatives. In HD patients, the R2 latency increase correlated significantly with the severity of facial chorea. The R2 abnormalities are probably caused by impaired suprasegmental control by the basal ganglia over brainstem interneurons, which may precede the onset of involuntary movements, probably conditioning the severity of facial chorea during development of the disease.

The blink reflex and the corneal reflex are followed by cortical activity resembling the nociceptive potentials induced by trigeminal laser stimulation in man.

Laser stimulation of the supraorbital regions evokes brain potentials (LEPs) related to trigeminal nociception. The aim of this study was to record the R2 component of the blink reflex and the corneal reflex in 20 normal subjects, comparing the scalp activity following these reflexes with the nociceptive potentials evoked by CO2 laser stimulation of supraorbital regions. Cortical and muscular reflexes evoked by stimulation of the first trigeminal branch were recorded simultaneously. The R2 component of the blink reflex and the corneal reflex were followed by two cortical peaks, which resembled morphologically N-P waves of LEPs. The two peaks demonstrated a difference in latency of approximately 40 ms, which is consistent with activation time of nociception. This finding suggests that these reflexes are induced by activation of small pain-related fibers.

The Migraine Disability Assessment (MIDAS) questionnaire: translation and reliability of the Italian version.

We have developed and tested an Italian version of the Migraine Disability Assessment (MIDAS) questionnaire, an established instrument for assessing headache-related disability. A multistep process was used to translate and adapt the questionnaire into Italian, which was then tested on 109 Italian migraine without aura patients, 86 (78.9%) of whom completed the form a second time 21 days later. Overall MIDAS score had good test-retest reliability (Spearman's correlation 0.77), closely similar to that found in English-speaking migraineurs, and individual responses were also satisfactorily reliable. Internal consistency was good (Cronbach's alpha 0.7). These findings support the use of the MIDAS questionnaire as a clinical and research tool with Italian patients.

The three responses of the blink reflex in adult and juvenile migraine.

Recent theories about migraine pathogenesis have emphasized the role of the trigeminal system in the pathogenesis of migraine attacks (Moskowitz, 1997). The blink reflex (BR) could be a suitable method to evaluate the trigeminal system in migraine, as it is generally elicited by stimulation of the trigeminal ophthalmic division (Kimura et al., 1967), involved in migraine attacks. Sixty one adult and 15 juvenile migraine without aura subjects were selected, in order to evaluate the BR features, including the subjective perceptive and pain thresholds and the R1, R2 and R3 components intensity thresholds and amplitudes. The electrophysiological procedure was carried out during the pain free phase. The findings were compared with those of 28 healthy controls, 18 adults and 10 children. In both adult and juvenile migraine sufferers an early appearance of the R3 response at almost the R2 threshold was observed in comparison with age-matched controls. Unfortunately, the anatomic and physiologic organization of the R3 component is uncertain: its early onset could suggest a dysfunction of the inhibitory control system on the trigeminal networks, which may predispose to migraine attacks.

Zolmitriptan reverses blink reflex changes induced during the migraine attack in humans.

The question about the 5-hydroxytryptamine (5-HT)(1B-1D) receptors agonists, if the clinical efficacy in migraine attacks is linked with the action at the central level or at the peripheral one, is still unresolved. We evaluated the effects of zolmitriptan and sumatriptan on blink reflex in thirty migraine without aura patients during the attacks in order to assess the central action on the trigeminal system. Both drugs were effective in reducing headache severity compared to placebo. In the migraine attack an increased area of the R3 component on the pain side was observed; it was suppressed by zolmitriptan, which confirmed its action on the central trigeminal circuits, though the clinical relevance of this effect could be questioned.

Clinical neurophysiology in childhood headache.

Electrophysiological studies in childhood headache are of interest because of the need to make a clinical diagnosis and also because of the efficacy of physiopathological studies in juvenile age attributable to the recent outcome of the illness, with less clinical modification by environmental factors or drug use. Electrophysiological studies in childhood headache are concerned with migraine and electroencephalographic (EEG) evaluations; evoked potentials, event-related potentials and, less often, electromyographic studies are also reported. Visual analysis of EEG suggests an association between migraine and epilepsy; quantitative EEG, visual and event-related evoked potentials show fluctuating abnormalities, depending on the occurrence of the migraine attacks and permanent anomalous patterns related to the basic mechanisms underlying the disease. Blink reflex studies might suggest a primary dysfunction of the nociceptive control central system in children affected by tension-type headache and migraine. The use of neurophysiological procedures in juvenile migraine is considered limited in clinical practice and of particular interest in neurophysiological studies of headache.

Psychiatric comorbidity and psychosocial stress in patients with tension-type headache from headache centers in Italy. The Italian Collaborative Group for the Study of Psychopathological Factors in Primary Headaches.

A multicenter study was carried out in 10 Italian Headache Centers to investigate the prevalence of psychosocial stress and psychiatric disorders listed by the IHS classification as the "most likely causative factors" of tension-type headache (TTH). Two hundred and seventeen TTH adult outpatients consecutively recruited underwent a structured psychiatric interview (CIDI-c). The assessment of psychosocial stress events was carried out using an ad hoc questionnaire. The psychiatric disorders that we included in the three psychiatric items of the fourth digit of the IHS classification were depressive disorders for the item depression, anxiety disorders for the item anxiety, and somatoform disorders for the item headache as a delusion or an idea. Diagnoses were made according to DSM-III-R criteria. At least one psychosocial stress event or a psychiatric disorder was detected in 84.8% of the patients. Prevalence of psychiatric comorbidity was 52.5% for anxiety, 36.4% for depression, and 21.7% for headache as a delusion or an idea. Psychosocial stress was found in 29.5% of the patients and did not differ between patients with and without psychiatric comorbidity. Generalized anxiety disorder (83.3%) and dysthymia (45.6%) were the most frequent disorders within their respective psychiatric group. The high prevalence of psychiatric disorders observed in this wide sample of patients emphasizes the need for a systematic investigation of psychiatric comorbidity aimed at a more comprehensive and appropriate clinical management of TTH patients.

Steady-state visual-evoked potentials in headache: diagnostic value in migraine and tension-type headache patients.

We tested the hypothesis that migraine and tension-type headache are separate disorders based on visual evoked potentials. We recruited 120 migraine without aura patients (MwoA), 64 tension-type headache patients (TTH), and 51 healthy controls. We performed discriminant analysis combined with a stepwise selection of predictors. Mean values of the F1 component were significantly increased over Fp1, C3, P4, O2 and O1 electrodes in MwoA and TTH patients compared with normal subjects. Only the control subjects were correctly distinguished. The increased brain response to visual stimulation detected in both MwoA and TTH may suggest a common neuronal dysfunction in the two headache subtypes.

Photic driving response in primary headache: diagnostic value tested by discriminant analysis and artificial neural network classifiers.

The aim of this study was to discriminate migraine patients (MWoA) from tension-type headache (TTH) patients and normals in order to confirm that the photic driving response in the medium frequency range is a marker of migraine and to test the hypothesis that MWoA and TTH are separate disorders based on electrophysiological pattern. We recruited 120 MWoA patients, 64 TTH patients, and 51 healthy controls without any history of headache or of migraine inheritance, according to International Headache Society (IHS) criteria. The classification method was discriminant analysis using both linear discriminant analysis with a stepwise selection of predictors and an artificial neural network classifier (NNs). The mean amplitude of the first harmonic elicited by flash stimulation in the 15-27 Hz range was significantly increased over Fp1, C3, C4, P4, O2, and O1 electrodes in MWoA and TTH patients in comparison with normal subjects. Using both classification methods, only the control subjects were correctly distinguished. When only the patient groups were matched, no significant difference was detectable. The increased brain response to visual stimulation detected in both migraine and TTH suggests a common neuronal dysfunction in the two headache subtypes.

Outcome of juvenile headache in outpatients attending 23 Italian headache clinics. Italian Collaborative Study Group on Juvenile Headache (Società Italiana Neuropsichiatria Infantile [SINPI]).

A multicenter 3-year follow-up study was carried out on young patients with headache referred to tertiary headache centers or pediatric clinics. Three years after the first examination in 1993, 442 (of an original sample of 719) young outpatients with headache (226 females and 216 males) were re-examined. The diagnostic criteria of the International Headache Society (IHS) and those modified for migraine without aura by Winner et al were applied at both the baseline evaluation and the 3-year re-examination. At the follow-up, 290 children still had headache, 101 were in clinical remission, and 51 had dropped out. Using the current diagnostic criteria, only 46.2% of patients having migraine without aura, 50% of those having migraine with aura, and 35.3% of those suffering from migraine disorders which do not fulfill IHS criteria for migraine received the same diagnosis at the time of follow-up. The percentage of patients receiving a diagnosis of migraine without aura rose significantly when new modified criteria were used (60.5%), whereas a drop in the frequency of migraine disorders not fulfilling IHS criteria was observed at follow-up, both in patients with the diagnosis of migraine without aura at the first examination (4.6%) and in patients with migraine not always fulfilling IHS criteria at the first examination (6.2%). Among all patients who received this latter diagnosis at the first examination, it was possible to make a diagnosis of migraine with aura at the follow-up in 8.8% of cases and that of migraine without aura in 26.5%. No significant variations in the frequency of either episodic tension-type headache or chronic tension-type headache were found, with the exception of a slight decrease in the percentage of tension-type headache which did not fulfill IHS criteria, but the difference between the first examination and the follow-up values does not reach the level of statistical significance (5% versus 12%). As far as the evolution of migraine is concerned, 17.4% of patients with migraine were headache-free at the 3-year follow-up. In tension-type headache, the percentage of patients who were headache-free was particularly high in those with the episodic form (32.9%) and in those suffering from tension-type headache not fulfilling IHS criteria (29.1%). The majority of patients who had been diagnosed as having unclassifiable headache at the first examination received a correct diagnosis at the follow-up with the exception of one patient. As observed in adult patients, variations in the headache characteristics were also observed in children and adolescents (that is, migraine with aura can change to migraine without aura, or the latter can transform into episodic tension-type headache or chronic tension-type headache can change into the episodic form). This follow-up study was aimed at reaching a better understanding of headache disturbances in children and adolescents, examining, in particular, variations of headache with time in this stage of life.

EEG spectral analysis in migraine without aura attacks.

In 16 patients suffering from migraine without aura, we examined quantitative EEG and steady-state visual evoked potentials (SSVEPs) at 27 Hz stimulation during the critical phase of migraine and in attack-free periods. The main spontaneous EEG abnormalities found during the critical phase were the slowing and asymmetry of the dominant frequency in the alpha range. The amplitude of the SSVEP F1 component was significantly reduced during the attack phase compared with the intercritical phase; in the latter condition the visual reactivity to 27 Hz stimulus was increased over almost the entire scalp compared with normal subjects. The EEG abnormalities confirm a fluctuating modification of alpha activity during the migraine attack, probably related to a functional disorder. The suppression of visual reactivity during the migraine attack could be related to a phenomenon of neuronal depolarization such as spreading depression, occurring in a situation of central neuronal increased excitability predisposing to migraine attacks.

Somatosensory evoked potentials in migraine.

Twenty-six patients suffering from migraine with aura and without aura were examined using somatosensory evoked potentials (SEPs) during the intercritical phase. The mean amplitude of the prerolandic component was significantly reduced in migraine patients with and without aura on the right hemisphere; the ratio between the parietal N20/P25 and the prerolandic P22/N30 was significantly enhanced in migraine groups over the left and the right hemisphere. A significant interside asymmetry of the N30 amplitude was observed in the migraine with aura group in comparison with control subjects. The occurrence of SEP abnormalities was not correlated with the age of the patients, with illness duration or with the frequency of migraine attacks. SEP abnormalities observed in migraine with and without aura may have an underlying primary neural disorder probably based on a chronic dopaminergic dysfunction.

Stress, mood disorders and memory in headache.

Comorbidity between headache and other disorders such as psychological or memory problems is a topic of increasing scientific interest both for us diagnostic and therapeutic implications but also for pathogenetic advances. A central neurogenic mechanism such as a dysregulation of some neurotransmitter system might underlie not only headache but also other coexistent disorders; findings highlight the role of serotonin pathways.

Discrimination between migraine patients and normal subjects based on steady state visual evoked potentials: discriminant analysis and artificial neural network classifiers.

Fifty-one migraine patients and 19 control subjects were examined by steady state visual evoked potentials (SSVEPs) procedure. The aim of this study was to develop a discriminant analysis and an artificial neural network (NN) classifier in order to discriminate between migraneurs during attack-free periods and normal subjects. Discriminant analysis correctly classified 72.5% of migraine patients with a false positive rate of 36.8%. The NN method had a sensitivity of 100% with a false positive rate of 15%. The results of this study confirm SSVEP pattern as a marker of migraine and demonstrate that NNs could be a useful method in the statistical analysis of topographic EEG data.