Migraine and fibromyalgia

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Response: Commentary: Cortical responses to salient nociceptive and not nociceptive stimuli in vegetative and minimal conscious state

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Management of Huntington’s disease: role of tetrabenazine

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder characterized by progressive involuntary movements, neuropsychiatric disturbances, and cognitive impairment. The use of tetrabenazine (TBZ), a specific inhibitor of vesicular monoamine transporter, is approved for chorea in HD patients. We aimed to review the medical literature concerning the efficacy and tolerability of TBZ in the treatment of HD patients and to report our personal experience about TBZ use in a cohort of HD patients. We searched PubMed (1960 to July 2010) using the following keywords: “tetrabenazine” + “huntington’s disease + chorea”. We included randomized controlled trials, open-label trials, and retrospective studies. We excluded case reports and studies conducted on fewer than 20 patients. In addition, we retrospectively evaluated 2 years’ follow-up of TBZ treatment on motor and cognitive performances and functional abilities in 28 HD patients, compared with 10 patients treated by other neuroleptics (clotiapine). Only four papers fulfilled the requested criteria. In the first study, which included 84 randomized outpatients, TBZ showed a significant improvement of chorea compared with placebo. In the open-label study extension, TBZ confirmed its efficacy on chorea, with a frequent occurrence of withdrawals due to side effects. In a retrospective study of long-term efficacy, 63 patients under TBZ therapy for an average period of 34 months showed a stable effect on chorea, despite a slight reduction of effect over time. In a telephone survey conducted on a total of 118 patients affected by different movement disorders, TBZ showed the most favorable effect for the 28 included HD patients. Our HD patients showed a slight deterioration of motor performances over time that was nonsignificant compared with TBZ or clotiapine treatments. Despite the fact that the global effect of TBZ seems positive in HD, more attention on evaluating symptomatic treatments for cognitive and psychiatric deterioration as well as motor deterioration would alleviate this devastating disorder until a neuroprotective treatment becomes available

Serum carcinoembryonic antigen pre-operative level in colorectal cancer: revisiting risk stratification

BackgroundResults Biomarkers may play a role as predictive and prognostic factors in colorectal cancer patients. The aims of the study were to verify the prognostic role of pre-operative serum carcinoembryonic antigen (CEA) level in predicting overall survival and risk of recurrence in a cohort of colorectal cancer patients and to evaluate optimal cut-off values.Methods A retrospective cohort analysis was performed on colorectal cancer patients undergoing elective curative surgery between 2004 and 2019 at an Italian Academic Hospital. Main outcomes were overall survival, disease-free survival at 3-years and risk of local, loco-regional and distant recurrence during follow-up. A receiver operating characteristic (ROC) curve analysis was plotted using CEA pre-operative values and follow-up data in order to estimate the optimal cut-off values.A total of 559 patients were considered. The mean CEA value was 12.1 +/- 54.1 ng/mL, and the median 29.3 (0-4995) ng/mL. The ROC curve analysis identified 12.5 ng/mL as the best CEA cut-off value to predict the risk of metastatic development after surgery in stage I-III colorectal cancer patients, and 10 ng/mL as the best CEA cut-off value to predict overall survival and disease-free survival in stage III-IV patients. These data suggest a stratification of colorectal cancer patients in three classes of risk: a low risk class (CEA <10 ng/mL), a moderate risk class (CEA 10-12.5 ng/mL) and a high risk class (CEA >12.5 ng/mL).Conclusion In conclusion, pre-operative serum CEA measurements could integrate information to enhance patient risk stratification and tailored therapy

Effects of onabotulintoxinA on habituation of laser evoked responses in chronic migraine

Onabotulintoxin A (BontA) is an efficacious preventive treatment for chronic migraine, though the specific mechanism of action is still under discussion. The study aims: (1) To evaluate pain processing modifications in chronic migraine patients (CM) under single BontA administration in pericranial muscles, by means of CO2 Laser Evoked Potentials (LEPs) obtained by the stimulation of the skin over the right frontal and trapezius injection sites and hand dorsum, in a double blind placebo controlled crossover design. (2) To correlate main LEPs findings with clinical outcome after one year of BontA treatment. Twenty refractory CM patients were included in the analysis. The LEPs were recorded in basal conditions and seven days after BontA (PREEMPT protocol) and saline solution injection. The N1, N2 and P2 amplitude and latencies and N2P2 habituation index were evaluated and correlated with the percent change of headache frequency after one year of toxin treatment. After seven days of BontA treatment, a normalization of the trigeminal habituation index was observed, which was correlated with the clinical outcome after one year of BontA therapy. Patients displaying trigeminal LEPs facilitation at T0 time showed a more efficient therapeutic outcome. Neurotoxin may exert a modulating effect on trigeminal nociception, normalizing central neurotransmission

Assessment of C Fibers Evoked Potentials in Healthy Subjects by Nd : YAP Laser

INTRODUCTION: Although laser stimuli activate both Ad- and C-fibres, the corresponding laser evoked potentials (LEPs) remain restricted to the Ad-fibers input, while the C-fibers related potential is hardly detectable. AIMS: To evaluate multichannel ultralate LEPs (U-LEPs) by using Nd : Yap laser pulses in healthy volunteers to stimulation of face and lower and upper limbs, in order to estimate the reliability of C-LEPs elicited from both trigeminal and somatic sites. METHODS: Twenty healthy volunteers participated in two stimulation sessions to record Aδ-LEPs and C-LEPs. We used a Nd : YAP Laser and 62 EEG recording electrodes. Stimuli parameters were set to activate either small myelinated (Aδ), eliciting purely warmth sensations, or unmyelinated (C) afferents, and eliciting pinprick sensations. RESULTS: At the trigeminal level, we obtained a negative-positive complex in a time interval compatible with the C fibers activation. In the somatic districts, the averaged responses consisted of an earlier negative-positive complex, followed by a later one. Single trials analysis of U-LEPs showed a maximal positive peak in a time interval in the range of C fibers. Topographical analysis of U-LEPs resembled that of LEPs. All subjects exhibited readable U-LEPs in at least 2 stimulated sites. Discussion. A purely warmth sensation seems to correspond to Aδ and C-fibers coactivation, at least in the somatic districts. While the related cortical waves seem hardly readable, their total absence could be a sign of systemic involvement of warm related C-fibers in specific clinical conditions

Noninvasive vagus nerve stimulation as acute therapy for migraine. The randomized PRESTO study

Objective: To evaluate the efficacy, safety, and tolerability of noninvasive vagus nerve stimulation (nVNS; gammaCore; electroCore, LLC, Basking Ridge, NJ) for the acute treatment of migraine in a multicenter, double-blind, randomized, sham-controlled trial. Methods: A total of 248 participants with episodic migraine with/without aura were randomized to receive nVNS or sham within 20 minutes from pain onset. Participants were to repeat treatment if pain had not improved in 15 minutes. Results: nVNS (n = 120) was superior to sham (n = 123) for pain freedom at 30 minutes (12.7% vs 4.2%; p = 0.012) and 60 minutes (21.0% vs 10.0%; p = 0.023) but not at 120 minutes (30.4% vs 19.7%; p = 0.067; primary endpoint; logistic regression) after the first treated attack. A post hoc repeatedmeasures test provided further insight into the therapeutic benefit of nVNS through 30, 60, and 120 minutes (odds ratio 2.3; 95% confidence interval 1.2, 4.4; p = 0.012). nVNS demonstrated benefits across other endpoints including pain relief at 120minutes and was safe and well-tolerated. Conclusion: This randomized sham-controlled trial supports the abortive efficacy of nVNS as early as 30 minutes and up to 60 minutes after an attack. Findings also suggest effective pain relief, tolerability, and practicality of nVNS for the acute treatment of episodic migraine

Effect of non-invasive vagus nerve stimulation on resting-state electroencephalography and laser-evoked potentials in migraine patients : mechanistic insights

A recent multicenter trial provided Class I evidence that for patients with an episodic migraine, non-invasive vagus nerve stimulation (nVNS) significantly increases the probability of having mild pain or being pain-free 2 h post-stimulation. Here we aimed to investigate the potential effect of nVNS in the modulation of spontaneous and pain related bioelectrical activity in a subgroup of migraine patients enrolled in the PRESTO trial by using resting-state electroencephalography and trigeminal laser-evoked potentials (LEPs). LEPs were recorded for 27 migraine patients who received active or sham nVNS over the cervical vagus nerve. We measured power values for frequencies between 1–100 Hz in a resting-state condition and the latency and amplitude of N1, N2, and P2 components of LEPs in a basal condition during and after active or sham vagus nerve stimulation (T0, T1, T2). The P2 evoked by the right and the left trigeminal branch was smaller during active nVNS. The sham device also attenuated the P2 amplitude evoked by the left trigeminal branch at T1 and T2, but this attenuation did not reach significance. No changes were observed for N1 amplitude, N1, N2, P2 latency, or pain rating. nVNS induced an increase of EEG power in both slow and fast rhythms, but this effect was not significant as compared to the sham device. These findings suggest that nVNS acts on the cortical areas that are responsible for trigeminal pain control and pave the ground for future studies aimed at confirming the possible correlations with clinical outcomes, including the effect on symptoms that are directly correlated with trigeminal pain processing and modulation

Dynamic causal modelling of the reduced habituation to painful stimuli in migraine : an EEG study

A consistent finding in migraine is reduced cortical habituation to repetitive sensory stimuli. This study investigated brain dynamics underlying the atypical habituation to painful stimuli in interictal migraine. We investigated modulations in effective connectivity between the sources of laser evoked potentials (LEPs) from a first to final block of trigeminal LEPs using dynamic causal modelling (DCM) in a group of 23 migraine patients and 20 controls. Additionally, we looked whether the strength of dynamical connections in the migrainous brain is initially different. The examined network consisted of the secondary somatosensory areas (lS2, rS2), insulae (lIns, rIns), anterior cingulate cortex (ACC), contralateral primary somatosensory cortex (lS1), and a hidden source assumed to represent the thalamus. Results suggest that migraine patients show initially heightened communication between lS1 and the thalamus, in both directions. After repetitive stimulations, connection strengths from the thalamus to all somatosensory areas habituated in controls whereas this was not apparent in migraine. Together with further abnormalities in initial connectivity strengths and modulations between the thalamus and the insulae, these results are in line with altered thalamo-cortical network dynamics in migraine. Group differences in connectivity from and to the insulae including interhemispheric connections, suggests an important role of the insulae