A trial of metoclopramide vs sumatriptan for the emergency department treatment of migraines.

Peer reviewe

Noninvasive peripheral vagal nerve stimulation prevents migraine aura: A case report

We describe a patient affected by migraine with visual and somatosensory aura, whose symptoms were consistently attenuated by noninvasive peripheral vagal nerve stimulation (nVNS) in multiple prospectively recorded attacks. When compared with the current standard of care, nVNS significantly reduced the duration of visual aura in all the attacks ( n = 5) and prevented the somatosensory aura in three of the five attacks. The overall duration of nVNS-treated auras was 19.0 ± 4.2 min, significantly shorter than the duration of aura in attacks treated with standard of care (103.8 ± 10.3 min). This single-case study requires confirmation in a larger sample size, but we believe that this first report is suggestive of likely efficacy given the relatively high number of treated attacks and the consistent effect of nVNS

Expression of Selected microRNAs in Migraine: A New Class of Possible Biomarkers of Disease?

Preliminary but convergent findings suggest a role for microRNAs (miRNAs) in the generation and maintenance of chronic pain and migraine. Initial observations showed that serum levels of miR-382-5p and miR-34a-5p expression were increased in serum during the migraine attack, with miR-382-5p increasing in the interictal phase as well. By contrast, miR-30a-5p levels were lower in migraine patients compared to healthy controls. Of note, antimigraine treatments proved to be capable of influencing the expression of these miRNAs. Altogether, these observations suggest that miRNAs may represent migraine biomarkers, but several points are yet to be elucidated. A major concern is that these miRNAs are altered in a broad spectrum of painful and non-painful conditions, and thus it is not possible to consider them as truly "migraine-specific" biomarkers. We feel that these miRNAs may represent useful tools to uncover and define different phenotypes across the migraine spectrum with different treatment susceptibilities and clinical features, although further studies are needed to confirm our hypothesis. In this narrative review we provide an update and a critical analysis of available data on miRNAs and migraines in order to propose possible interpretations. Our main objective is to stimulate research in an area that holds promise when it comes to providing reliable biomarkers for theoretical and practical scientific advances

The effects of intensive neurorehabilitation on sequence effect in Parkinson's disease patients with and without freezing of gait

Background: The sequence effect (SE), defined as a reduction in amplitude of repetitive movements, is a common clinical feature of Parkinson's disease (PD) and is supposed to be a major contributor to freezing of gait (FOG). During walking, SE manifests as a step-by-step reduction in step length when approaching a turning point or gait destination, resulting in the so-called destination sequence effect (dSE). Previous studies explored the therapeutic effects of several strategies on SE, but none of them evaluated the role of an intensive rehabilitative program. Objectives: Here we aim to study the effects of a 4-week rehabilitative program on dSE in patients with PD with and without FOG. Methods: Forty-three patients (30 males, 70.6 \ub1 7.5 years old) with idiopathic PD were enrolled. The subjects were divided into two groups: patients with (PD + FOG, n = 23) and without FOG (PD - FOG, n = 20). All patients underwent a standardized 4-week intensive rehabilitation in-hospital program. At hospital admission (T0) and discharge (T1), all subjects were evaluated with an inertial gait analysis for dSE recording. Results: At T0, the dSE was more negative in the PD + FOG group (-0.80 \ub1 0.6) when compared to the PD - FOG group (-0.39 \ub1 0.3) (p = 0.007), even when controlling for several clinical and demographic features. At T1, the dSE was reduced in the overall study population (p = 0.001), with a more pronounced improvement in the PD + FOG group (T0: -0.80 \ub1 0.6; T1: -0.23 \ub1 0.4) when compared to the PD - FOG group (T0: -0.39 \ub1 0.3; T1: -0.22 \ub1 0.5) (p = 0.012). At T1, we described in the overall study population an improvement in speed, cadence, stride duration, and stride length (p = 0.001 for all variables). Conclusions: dSE is a core feature of PD gait dysfunction, specifically in patients with FOG. A 4-week intensive rehabilitative program improved dSE in PD patients, exerting a more notable beneficial effect in the PD + FOG group

OnabotulinumtoxinA reduces temporal pain processing at spinal level in patients with lower limb spasticity

Spasticity is a muscle tone disorder associated with different neurological conditions. Spasticity could be associated with pain, high disability, poor functional recovery, and reduced quality of life. Botulinum neurotoxin type A (BoNT-A) is considered a first-line treatment for spasticity and, more recently, it also represents a therapeutic option for various chronic pain conditions. In this open label study, we aim to evaluate the effect of the BoNT-A on the spinal nociception in patients affected by spasticity of the lower limbs with associated pain with predominantly neuropathic features. Ten patients with stroke, 10 with multiple sclerosis and 5 with spinal cord injury were enrolled in the study. They were tested with clinical scales (neuropathic pain scale inventory (NPSI), numerical rating scale (NRS), modified Ashworth scale (MAS) and with the nociceptive withdrawal reflex at lower limbs to explore the spinal temporal summation threshold at baseline and 30 day after BoNT-A injection. OnabotulinumtoxinA (50 to 200 units per site) was injected in the lower limb muscles according to the distribution of spasticity. No significant differences were found at baseline for neurophysiological features across groups. After the BoNT-A injection, we recorded a significant reduction in MAS and NRS scores. Regarding the neurophysiological parameters, we described a significant increase in the temporal summation threshold after the BoNT-A injection. Our data supports the hypothesis that peripherally injected OnabotulinumtoxinA modulates the excitability of spinal cord nociceptive pathways. This activity may take place irrespective of the effect of the drug on spasticity

Negative Short-Term Outcome of Detoxification Therapy in Chronic Migraine With Medication Overuse Headache: Role for Early Life Traumatic Experiences and Recent Stressful Events

Background: Early traumatic experiences and Stressful episodes appear to be associated to the development and perpetuation of chronic pain disorders and to dependence-related behaviors.Objective: The present study evaluated whether these factors can be predictors, together with psychiatric conditions, of the outcome of a detoxification treatment in patients suffering from chronic migraine and medication-overuse headache in a 2-month follow-up.Methods: Consecutive patients undergoing a detoxification program as therapy for treating chronic migraine and medication overuse headache at the Pavia Headache Center were analyzed. During this program, lasting about 1 week, all patients received the standard CARE in-patient withdrawal protocol, which consisted in discontinuing abruptly the overused drug(s) and receiving daily detoxification therapy. Data on childhood traumatic events and recent stressful ones were analyzed by means of the Childhood Trauma Questionnaire and Stressful life-events Questionnaire. Psychiatric conditions were evaluated using the Structured Clinical Interview for Diagnostic and Statistical Manual of mental disorders.Results: A total of 166 (80% females; mean age 44.7) patients completed the follow-up at 2 months after the detoxification program: of these 118 (71%) (78% females; mean age 44.7) stopped overuse and reverted to an episodic pattern of headache (Group A); 19 (11%) (89% females; mean age 41.3) kept overusing and maintained a chronic pattern of headache (Group B); and 29 (18%) (79% females; mean age 46.9) stopped overuse without any benefit on headache frequency (Group C). At the multivariate analyses, a higher number of early life emotional distress (Odds Ratio 11.096; p = 0.037) arose as a prognostic factor for the outcome in Group B, while major depression during life-time (Odds Ratio 3.703; p = 0.006) and higher number of severe stressful episodes in the past 10 years (Odds Ratio 1.679; p = 0.045) were prognostic factors for the outcome of Group C.Conclusions: Data suggest that early life traumas and stressful events have a negative impact on the outcome of the detoxification program in subjects overusing acute medication for headache. The history of emotional childhood traumas is associated to the failure to cease overuse, whereas recent very serious life events are associated to the persistence of headache chronicity

Neurostimulation therapy in intractable headaches.

A proportion of chronic headache patients become refractory to medical treatment and severely disabled. In such patients various neurostimulation methods have been proposed, ranging from invasive procedures such as deep-brain stimulation to minimally invasive ones like occipital nerve stimulation. They have been applied in single cases or small series of patients affected with varying headache disorders: cervicogenic headache, hemicrania continua, posttraumatic headache, chronic migraine, and cluster headache. Although favorable results were reported overall, it is premature to consider neurostimulation as a treatment with established utility in refractory headaches. At present, the most detailed clinical studies have been performed in intractable chronic cluster headache (iCCH) patients, who represent about 1% of all chronic cluster headache (CCH) patients. Various lesional interventions have been attempted in these patients, none with lasting benefits. In recent years, non-destructive neurostimulation methods have raised new hope. Hypothalamic deep-brain stimulation (hDBS) acts rapidly and has lasting efficacy, but is not without risk. Occipital nerve stimulation (ONS) was studied in two trials on a total of 17 iCCH patients. Clinical efficacy was found to be very satisfactory by most patients and by the investigators. Although slightly less efficacious than hDBS, ONS has the advantage of being rather harmless and reversible. At this stage, it should be preferred as first-line invasive therapy for iCCH. Recent case reports mention the efficacy of supraorbital (SNS) and vagal (VNS) nerve stimulation. Whether these neurostimulation methods have a place in the management of iCCH patients remains to be determined