Catello Vollono

Topiramate in migraine prophylaxis: A randomised double-blind versus placebo study

The objectives of this paper are to evaluate the efficacy and tolerability of topiramate, given at the dose of 100 mg/day, in the prophylactic treatment of migraine. The hypothesis that migraine is the result of a condition of neuronal hyperexcitability and the quest for drugs that are able to limit the number of crises justifies the attempt to utilise the new antiepileptic drugs in the prophylaxis of this pathology, which is so important due to its high prevalence and due to the high disability it causes. The study was randomised double-blind versus placebo, lasting 16 weeks, and was preceded by a run-in period of 4 weeks. One hundred and fifteen patients were randomly allocated to treatment with topiramate (TPM) or placebo: 35 patients completed the study in the TPM group and 37 patients in the placebo group. At the end of the double-blind phase of study, in the TPM group, we recorded a significant reduction in the frequency of migraine crises (from 5.26 at baseline to 2.60 in the last 4 weeks), a significant reduction in the quantity of symptomatic drugs taken as compared to the placebo control group (from 6.17±1.80 SD to 2.57±0.80) and a significant downward trend in the number of days of disability over the 16-week period of therapy. In the TPM group, side effects were transient and well tolerated. TPM has thus proven its efficacy and tolerability in the prophylaxis of migraine.

Topiramate and triptans revert chronic migraine with medication overuse to episodic migraine

Objective: This is a randomized, double-blind versus placebo study aimed at evaluating the efficacy of topiramate (TPM) in reducing the number of days with headache and the amount of acute medication taken monthly in patients with chronic migraine with medication overuse. We also studied the efficacy of single triptans available in Italy in interrupting headache crises during preventive treatment. Methods: The studied sample was made up of 50 subjects: 30 patients were randomized for treatment with TPM, 100 mg/d, and 20 for placebo. Subjects treated with TPM were further randomized to evaluate, in double-blind versus placebo, the efficacy of single triptans available in Italy. The double-blind phase consisted of a titration phase (4 weeks) and of a maintenance phase (8 weeks). Outcome Measures: The reduction in the number of days with headache per 28 days and the reduction in the amount of acute medication taken per 28 days throughout the clinical trial in the TPM group were compared with those of the placebo group; the number of patients who were pain-free at 2 hours after the triptan intake and the headache recurrence rate in the 22 hours after the pain-free condition in the triptan group were compared with those of the placebo group. We also looked at tolerability profile. Results: The group treated with TPM had a significant reduction in the number of days with headache (P < 0.0001 vs placebo) and in the mean amount of acute medication taken (P < 0.0001 vs placebo); all triptans were superior to placebo; there were no significant differences between different triptans; the analgesic effect of triptans increased throughout the trial. Conclusions: Topiramate proved to be well tolerated and effective in reverting chronic migraine with medication overuse to episodic migraine.

Influence of cholinergic circuitries in generation of high-frequency somatosensory evoked potentials

OBJECTIVE High-frequency oscillations (HFOs) evoked by upper limb stimulation reflect highly synchronised spikes generated in the somatosensory human system. Since acetylcholine produces differential modulation in subgroups of neurons, we would determine whether cholinergic drive influences HFOs. METHODS We recorded somatosensory evoked potentials (SEPs) from 31 scalp electrodes in 7 healthy volunteers, before and after single administration of rivastigmine, an inhibitor of central acetylcholinesterase. Right median nerve SEPs have been analysed after digital narrow bandpass filtering (500-700 Hz). Raw data were further submitted to Brain Electrical Source analysis (BESA) to evaluate the respective contribution of lemniscal, thalamic and cortical sources. Lastly, we analysed by Fast Fourier transform spectral changes after drug administration in the 10-30 ms latency range. RESULTS Rivastigmine administration caused a significant increase of HFOs in the 18-28 ms latency range. Wavelets occurring before the onset latency of the conventional N20 SEP did not show any significant change. A similar increase concerned the strength of cortical dipolar sources in our BESA model. Lastly, we found a significant power increase of the frequency peak at about 600 Hz in P3-F3 traces after drug intake. CONCLUSIONS Our findings demonstrate that the cortical component of HFOs is significantly enhanced by cholinergic activation. Pyramidal chattering cells, which are capable to discharge high-frequency bursts, are mainly modulated by cholinergic inputs; by contrast, acetylcholine does not modify the firing rate of fast-spiking GABAergic interneurons. We thus discuss the hypothesis that cortical HFOs are mainly generated by specialised pyramidal cells.

Dysfunction of arousal systems in sleep-related migraine without aura

Primary headaches are closely related to sleep. Modifications in the patterns of arousal during sleep have been reported in migraine, especially in the nights preceding a headache attack. We aimed at evaluating the pattern of arousal from sleep in a group of patients affected by sleep-related migraine. We enrolled 10 consecutive patients, three males and seven females, aged between 20 and 62 years, who presented frequent attacks of migraine without aura (more than five per month), closely related to sleep (more than one-half of the attacks occurred during sleep, causing an awakening). A control group was studied, matched for age and sex. Patients and controls underwent a full-night polysomnographic study, following adaptation; arousal pattern was studied by the scoring of the high-frequency EEG arousal and by the cyclic alternating pattern (CAP). Migraineurs showed a lower CAP rate in non-rapid eye movement (NREM) sleep and, in particular, a lower number of A1 phases (low-frequency, high-amplitude EEG bursts) compared with the controls. Migraineurs also showed a lower index of high-frequency EEG arousals during rapid eye movement (REM) sleep. The reduction in the CAP rate indicates a lower level of arousal fluctuation in NREM sleep. The reduced arousal index in REM suggests a dysfunction in neural structures involved in both the control of REM sleep and the pathophysiology of migraine, such as the hypothalamus and the brainstem.

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

&NA; 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 A&dgr;‐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 A&dgr; afferents.

Migraine equivalents as part of migraine syndrome in childhood

BACKGROUND Migraine equivalents are common clinical conditions without a headache component, occurring as repeated episodes with complete remission between episodes. They include abdominal migraine, cyclical vomiting, benign paroxysmal vertigo, and benign paroxysmal torticollis. Other clinical entities, such as motion sickness and limb pain have been associated with migraine. We aimed to investigate the prevalence of migraine equivalents in a large population of children referred to a pediatric headache center and to analyze the possible relationship between migraine equivalents and headache features. METHODS A total of 1134 of children/adolescents (73.2% with migraine and 26.8% with tension-type headache) were included. Patients were divided into two groups according to the episode frequency (high and low). Pain intensity was rated on a three-level graduate scale (mild, moderate, and severe pain). RESULTS Migraine equivalents were reported in 70.3% of patients. Abdominal migraine (48.9%), limb pain (43.9%), and motion sickness (40.5%) were the most common migraine equivalents. Although headache type (migraine or tension-type headache) did not correlate with migraine equivalents presence (χ(2) = 33.2; P = 0.27), high frequency of headache episodes correlated with the occurrence of migraine equivalents. Moreover, migraine equivalents indicated a protective role for some accompanying feature of the headache episode. CONCLUSIONS Our results suggest that migraine equivalents should not be considered merely as headache precursors, but they as part of the migrainous syndrome. Thus, their inclusion among the diagnostic criteria for pediatric migraine/tension-type headache is useful.

Habituation to Pain in “Medication Overuse Headache”: A CO2 Laser-Evoked Potential Study

(Headache 2012;52:792‐807)

The abnormal recovery cycle of somatosensory evoked potential components in children with migraine can be reversed by topiramate

The aim of this study was to compare the recovery cycle of somatosensory evoked potentials (SEPs) in children with migraine without aura before and after treatment with topiramate. Eleven migraine children were studied before and after a 3-month treatment with topiramate at the average dose of 1.3 mg/kg/day. We calculated the SEP latency and amplitude modifications after paired electrical stimuli at 5, 20 and 40 ms interstimulus intervals, comparing them with a single stimulus condition assumed as baseline. In nine patients, who had a significant reduction in headache frequency after treatment, the recovery cycles of the P24 (P = 0.03) and N30 (P < 0.005) potentials were longer after than before topiramate treatment. In two migraineurs who did not show any improvement, the recovery cycles of the cortical SEP components were even shorter after treatment. Our results suggest that topiramate efficacy in paediatric migraine prophylaxis is probably related to restored cortical excitability.

Non-Epileptic Seizures (NES) are predicted by depressive and dissociative symptoms

OBJECTIVES (1) To measure depressive and dissociative symptoms in a population of patients with Non-Epileptic Seizures (NES, or pseudo-seizures); (2) To compare NES with Epileptic subjects and Normal controls; (3) To try to define a personality profile specific, or typical, of NES patients. METHODS PATIENTS 30 consecutive patients (21 females and 9 males, mean age 32.9+/-11.7 years) with NES diagnosed on clinical basis and confirmed by video-EEG recording; 30 patients with epilepsy matched for age and sex who had presented at least two seizures in the 12 months prior to the study despite pharmacological treatment; 30 Control subjects, healthy volunteers, matched for age and sex. Psychometric evaluation: Hamilton Rating Scale for Depression (HDRS), Dissociative Experience Scale (DES), Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Groups were compared by means of one-way Analysis of Variance (ANOVA) for independent samples, followed by posthoc Tukey HSD Test, with Bonferroni correction for multiple comparisons. RESULTS Depressive and dissociative symptoms showed a significantly higher prevalence in the NES group as compared to Epileptics (p<0.001) and Controls (p<0.001), whereas patients with epilepsy did not differ from Controls. The analysis of the MMPI-2 in NES group showed a general increase in most MMPI-2 T-scores as compared to Epileptics and Controls, rather than a constant elevation (T-score>70) of one or more scales. No specific personality profile could be identified for the NES group. CONCLUSIONS Our results are consistent with the hypothesis that depression and dissociative mechanisms are important precursors to the development and expression of NES.

Sleep quality in Facioscapulohumeral muscular dystrophy

OBJECTIVE To evaluate the subjective sleep quality, the prevalence of daytime sleepiness and the risk of sleep-related upper airways obstruction in patients with genetically proven Facioscapulohumeral muscular dystrophy (FSHD). FSHD is an autosomal dominant myopathy, characterized by an early involvement of facial and scapular muscles with eventual spreading to pelvic and lower limb muscles. PATIENTS AND METHODS Forty-six patients were enrolled, 27 women and 19 men, mean age 43.6+/-14.1 years. Study protocol included: a Clinical Severity Scale (CSS) for FSHD, Pittsburgh Sleep Quality Index (PSQI), Italian version of the Epworth Sleepiness Scale (ESS) and the search for clinical predictors of sleep-related airways obstruction. RESULTS Twenty-seven patients presented snoring, 12 reported respiratory pauses during sleep. One half (23/46) had PSQI scores above the normal threshold (=5). Correlations were found between the CSS and: the total PSQI score, the components C1 sleep quality, C5 sleep disturbances, C7 daytime dysfunction. CONCLUSION Our data support the hypothesis that patients with FSHD have an impaired sleep quality, and that this impairment is directly related to the severity of the disease. A systematic polysomnographic evaluation of these patients will be necessary to confirm the presence of sleep disruption and to clarify its pathogenesis.