Nociceptive inputs transmission in Huntington's disease: a study by laser evoked potentials.

The aim of the present study was to evaluate pain perception and evoked responses by laser stimuli (LEPs) in mild not demented Huntington's Disease (HD) patients. Twenty-eight HD patients and 30 control subjects were selected. LEPs were obtained by four scalp electrodes, (Fz, Cz, referred to the nasion; T3, T4, referred to Fz), stimulating the dorsum of both hands. All patients were also evaluated by somatosensory evoked potentials (SEPs) by median nerve stimulation. Only 3 patients referred pain of arthralgic type. Laser pain perception was similar between HD patients and controls. An abnormal N2, P2 and N1 latency increase was evident in the majority of HD patients. LEPs features were similar between patients taking and not taking neuroleptics. The N2 and P2 latencies, showed a negative correlation with functional score and Mini Mental State Examination, and a positive correlation with the severity of hyperkinetic movements. A delay in nociceptive input processing emerged in HD, concurring with the main features of the disease, in absence of clinical evidence of abnormalities in pain perception. The dysfunction of pain signals transmission in HD may induce sub-clinical changes of sensory functions, which may probably interfere with sensory-motor integration and contribute to functional impairment.

Detection of subclinical brain electrical activity changes in Huntington's disease using artificial neural networks.

OBJECTIVE: The aim of this study was to analyze EEG background activity in Huntington's disease (HD) patients and relatives at risk, in relation to CAG repeat size and clinical state, in order to detect an electrophysiological marker of early disease. METHODS: We selected 13 patients and 7 subjects at risk. Thirteen normal subjects, sex- and age-matched, were also evaluated. Artifact-free epochs were selected and analyzed through Fast-Fourier Transform. EEG background activity was tested using both linear analysis and artificial neural network (ANN) classifier in order to evaluate whether EEG abnormalities were linked to functional changes preceding the onset of the disease. RESULTS: The most important EEG classification pattern was the absolute alpha power not correlated with cognitive decline. The ANN correctly classified 11/13 patients and 12/13 normals. Moreover, the neural scores for subjects at risk seemed to be correlated to the expected time before the onset of the disease. CONCLUSIONS: ANN is a very powerful method to discriminate between normals and patients. It could be used as an automatic diagnostic tool. EEG changes in positive gene-carriers for HD confirm an early functional impairment which should be taken into account in the genetic counseling and in the management of the early stages of the disease.

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.

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 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.

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.

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.

Topographic classification of EEG patterns in Huntington's disease.

The aim of this study is to perform a topographic classification of electroencephalographic (EEG) patterns in subjects affected by the Huntington's disease (HD). The alpha activity is a discriminating feature for HD, as its amplitude reduction turns out to be a clear mark of the illness. When used as input variable to a supervised neural network, a good classification of pathological patterns and control ones is achieved with high values of sensitivity and specificity. It should be useful to get more insight into the local discriminating capabilities of the alpha rhythm by implementing a neural network approach to classify EEG patterns extracted from groups of channels corresponding to specific regions of the scalp. Receiver operating characteristic (ROC) curve analysis enables one to label each region with the value of the area under the curve, thus providing a local significance for HD classification. A reduction of the area when processing regions of the scalp, with respect to the whole, suggests that all channels provide significant contribution to HD pattern discrimination. These results can be interpreted as an effect of an abnormal subcortical modulation of the alpha rhythm, due to the dysfunctional action of the thalamus on the cortical activities. In a further study, morphometric features of thalamus and basal ganglia, evaluated by MRI, will be matched with the electrophysiological findings.

Effects of symptomatic treatments on cutaneous hyperalgesia and laser evoked potentials during migraine attack.

Previously an amplitude enhancement of laser evoked potentials (LEPs) was detected during migraine attack: we further examined pain threshold to CO2 laser stimuli and LEPs during attacks, evaluating the effect of almotriptan, lysine-acetylsalicylate and placebo treatment on cutaneous hyperalgesia to thermal stimuli delivered by CO2 laser and on LEP components. Eighteen patients suffering from migraine without aura were analysed. They were divided into three groups of six patients each, randomly assigned to lysine acetyl-salicylate, almotriptan or placebo treatments. The supraorbital zones and the dorsum of the hand were stimulated on both the symptomatic and not symptomatic side in all patients. The LEPs were recorded by 25 scalp electrodes. During attacks, the P2 wave was significantly enhanced; the amplitude of the P2 component obtained by the stimulation of the supraorbital zone during the attack on the side of the headache was significantly correlated with the intensity of pain and the frequency of headache. Both almotriptan and lysine acetyl-salicylate significantly reduced the P2 amplitude but they showed no effects on hyperalgesia to laser stimulation; headache relief following therapy was correlated with the reduction of the P2 amplitude. The cortical elaboration of laser-induced experimental pain seemed increased during migraine attack, and the severity of headache was mainly related to the increase of the later LEPs components expressing the attentive and emotive compounds of suffering. Reversion of this process appeared to be primarily responsible for the efficacy of drugs in treating migraine, though both almotriptan and lysine-acetil salicilate seemed to have no effect in reducing sensitization at second and third order nociceptive neurons.

Photic driving in migraine: correlations with clinical features.

Fifty-eight migraineurs were studied by intermediate frequency steady-state visual evoked potentials (SSVEPs) during headache-free periods. Sex, age, age of onset of migraine, duration of illness, type of migraine, side of pain, sleep-wake disorders, and frequency of migraine attacks did not correlate with any SSVEP abnormalities. On the other hand, visual responsiveness was significantly increased in subjects with family history of migraine, and in those with autonomic symptoms. Our results may indicate that a genetic predisposition to migraine underlies the observed abnormal visual response in migraineurs.

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.

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.

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.

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.

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.