Patterns of habituation and clinical fluctuations in migraine.

BACKGROUND: Habituation deficit, suggesting a deregulation of cortical excitability, represents a typical hallmark of interictal stages of migraine. We previously demonstrated that several neurophysiological markers of altered cortical excitability are significantly correlated to spontaneous clinical fluctuations of migraine. We therefore aimed at verifying whether clinical fluctuations are correlated to specific patterns of somatosensory evoked potential (SEP) habituation. METHODS: We analyzed habituation after median nerve stimulation of both high-frequency oscillations (HFOs) and N20 SEP in 25 migraine patients and 18 healthy volunteers. Subjects underwent six consecutive series of 500 stimuli. RESULTS: Migraine patients as a whole showed a significant habituation deficit of the N20 response. Moreover, spontaneously worsening patients show a clear potentiation of this wave in the last block of stimuli, whereas in spontaneously improving patients the N20 amplitude remained stable. Presynaptic HFOs were smaller in worsening patients and larger in improving ones, but they did not undergo habituation in patients as well as in healthy subjects. CONCLUSIONS: Potentiation of the N20 response in spontaneously worsening migraineurs confirms that the reduction of the thalamocortical drive plays a major role in migraine pathogenesis. Moreover, the stable pattern we observed in spontaneously improving patients suggests that compensatory mechanisms can also play an important role. The normal response to repeated stimuli of HFOs in migraineurs might indicate that, although its initial amount depends on clinical conditions, high-frequency thalamocortical drive remains stable during the stimulation and probably reflects the activity of a buffer mechanism.

Habituation to pain in "medication overuse headache": a CO2 laser-evoked potential study.

OBJECTIVE: Our aim was to investigate CO(2) laser-evoked potential (LEP) habituation to experimental pain in a group of patients affected by medication-overuse headache, with a history of episodic migraine becoming chronic, before and after treatment, consisting in acute medication withdrawal and a preventive treatment cycle. BACKGROUND: One of the main features of LEPs in migraineurs is a lower habituation to repetitive noxious stimuli during the interictal phase. METHODS: LEPs were recorded to stimulation of both the right hand and the right perioral region in 14 patients and in 14 healthy subjects. The habituation of both the N1 and the vertex N2/P2 components was assessed by measuring the LEP amplitude changes across 3 consecutive repetitions of 30 trials each. RESULTS: In the 8 patients who had clinically improved after treatment, the N2/P2 amplitude habituation was significantly higher after treatment than before treatment following both hand (F = 43.2, P < .0001) and face stimulation (F = 6.9, P = .01). In these patients, the N2/P2 amplitude habituation after treatment was not different from that obtained in healthy controls (P = .18 and P = .73 for hand and face stimulation, respectively). On the contrary, in the patients who did not improve, the N2/P2 amplitude still showed reduced habituation after both hand (F = 3.1, P = .08) and face (F = 0.7, P = .4) stimulation. CONCLUSION: The deficient habituation of the vertex N2/P2 complex was partly restored after successful treatment of medication-overuse headache, reflecting a modification in pain-processing pathways.

Abnormal Circadian Modification of Aδ-Fiber Pathway Excitability in Idiopathic Restless Legs Syndrome.

Restless legs syndrome (RLS) is characterized by unpleasant sensations generally localized to legs, associated with an urge to move. A likely pathogenetic mechanism is a central dopaminergic dysfunction. The exact role of pain system is unclear. The purpose of the study was to investigate the nociceptive pathways in idiopathic RLS patients. We enrolled 11 patients (mean age 53.2 ± 19.7 years; 7 men) suffering from severe, primary RLS. We recorded scalp laser-evoked potentials (LEPs) to stimulation of different sites (hands and feet) and during two different time conditions (daytime and nighttime). Finally, we compared the results with a matched control group of healthy subjects. The Aδ responses obtained from patients did not differ from those recorded from control subjects. However, the N1 and the N2-P2 amplitudes' night/day ratios after foot stimulation were increased in patients, as compared to controls (N1: patients: 133.91 ± 50.42%; controls: 83.74 ± 34.45%; p = 0.016; Aδ-N2-P2: patients: 119.15 ± 15.56%; controls: 88.42 ± 23.41%; p = 0.003). These results suggest that RLS patients present circadian modifications in the pain system, which are not present in healthy controls. Both sensory-discriminative and affective-emotional components of pain experience show parallel changes. This study confirms the structural integrity of Aδ nociceptive system in idiopathic RLS, but it also suggests that RLS patients present circadian modifications in the pain system. These findings could potentially help clinicians and contribute to identify new therapeutic approaches.

Somatosensory evoked potentials reflect the upper limb motor performance in multiple sclerosis.

OBJECTIVE: The aim of this multicentric study was to multidimensionally evaluate the relationship among somatosensory evoked potentials (SEPs) parameters, patient's perspective and clinical measures of the upper limb impairment in patients with multiple sclerosis (MS). METHODS: We consecutively enrolled 39 MS patients. For median nerve SEPs we acquired the N9, P14, N20 responses and the N9-P14 and P14-N20 interpeak latencies on the dominant side. We also used a validated patient-oriented questionnaire (Disabilities of the Arm, Shoulder and Hand - DASH) and a test of dexterity quantification as the 9-Hole Peg Test (9-HPT). RESULTS: A significant longer time to complete the 9-HPT (p<0.00006) was observed in patients with abnormal SEPs. Patients with undetectable N20 or P14 responses performed the 9-HPT in a significant longer time than patients with detectable responses (p<0.0006 and p<0.001 respectively). Concerning the perspective of patient (evaluated with the DASH questionnaire) significant differences in patients with undetectable P14 response (p<0.01) were observed. CONCLUSIONS: Our data provide further information useful for interpretation of SEPs results, being the median nerve SEPs related to the upper limb performance in MS patients. SIGNIFICANCE: These data increase the significance of SEPs both in clinical practice and in experimental studies in MS.

Coronary microvascular function and cortical pain processing in patients with silent positive exercise testing and normal coronary arteries.

ST-segment depression during exercise stress testing in asymptomatic subjects showing normal coronary arteries is considered a "false-positive" result. Coronary microvascular dysfunction, however, might be a possible cause of ST-segment depression in these cases. We assessed the coronary blood flow response to adenosine and to cold pressor test in the left anterior descending artery, using transthoracic Doppler echocardiography in 14 asymptomatic subjects with exercise-induced ST-segment depression and normal coronary arteries (group 1), 14 patients with microvascular angina (group 2), and 14 healthy subjects (group 3). Flow-mediated dilation was assessed in the brachial artery. Central pain processing was assessed using cortical laser evoked potentials during chest and right hand stimulation with 3 sequences of painful stimuli. The coronary blood flow response to adenosine was 1.8 ± 0.4, 1.9 ± 0.5, and 3.1 ± 0.9 in groups 1, 2, and 3, respectively (p <0.001). The corresponding coronary blood flow responses to the cold pressor test were 1.74 ± 0.4, 1.53 ± 0.3, and 2.3 ± 0.6 (p <0.001). The flow-mediated dilation was 5.5 ± 2.3%, 4.6 ± 2.4%, and 9.8 ± 1.2% in the 3 groups, respectively (p <0.001). The laser evoked potential N2/P2 wave amplitude decreased throughout the 3 sequences of stimulation in groups 1 and 3 but not in group 2 (chest, -19 ± 22%, +11 ± 42% and -36 ± 12%, p <0.001; right hand, -22 ± 25%, +12 ± 43% and -30 ± 20%, p = 0.009; in groups 1, 2, and 3). In conclusion, exercise stress test-induced ST-segment depression in asymptomatic subjects with normal coronary arteries cannot be considered as a simple false-positive result, because it can be related to coronary microvascular dysfunction. The different symptomatic state compared to patients with microvascular angina can, at least in part, be explained by differences in cortical processing of neural pain stimuli.

Mechanisms of neuropathic pain in patients with Charcot-Marie-Tooth 1 A: a laser-evoked potential study.

Charcot-Marie-Tooth (CMT) disease is the most common inherited neuropathy. The CMT1A type can be considered the typical phenotype of this disease. Although pain is not considered a relevant symptom in CMT patients by physicians and no study assessed it comprehensively, this symptom is frequently complained by patients. The objective of the present study was to investigate the nociceptive system in a sample of CMT1A patients suffering from pain by laser-evoked potentials (LEPs). Moreover, we also used a pain specific questionnaire in order to obtain patient-oriented data about their painful symptoms, the Neuropathic Pain Diagnostic Questionnaire (DN4). We evaluated 16 patients affected by CMT1A and 14 controls. All subjects underwent a standard LEP recording session (foot, hand, and face stimulation) and filled in the DN4. While the N2/P2 amplitude to foot stimulation was lower in CMT patients than in controls (p=0.003), no difference in LEP amplitude to both hand and face stimulation was found between patients and healthy subjects (p>0.05). This result is probably due to a length-dependent Adelta-fiber loss which involves mostly the longer fibers coming from the lower limb. In our patients, there was a significant association between a reduced N2/P2 amplitude to foot stimulation and a high DN4 score (p=0.03), meaning that patients with highly probable neuropathic pain had also low N2/P2 amplitude values to painful foot stimulation. This suggests that in our CMT1A patients neuropathic pain is probably related to a reduction of the Adelta afferents.