Beyond Pain: The Effects of OnabotulinumtoxinA Therapy on Sensitization and Interictal Symptoms in Chronic Migraine.

Chronic migraine is a disease with a high burden on patients from both a working and quality of life point of view. The pathophysiology of this subtype of migraine is due to several factors, such as medication overuse. Nevertheless, the detrimental recurring of headache attacks with central and peripheral sensitization plays a central role and explains some additional symptoms complained about by these patients even in the interictal phase. OnabotulinumtoxinA is a therapy indicated for chronic migraine since it has proven to reduce peripheral sensitization, showing even efficacy on central symptoms. The aim of this narrative review is to present the current evidence regarding the effect of OnabotulinumtoxinA on sensitization and interictal symptoms.

Pediatric Migraine and Visual Cortical Excitability: A Prospective Observational Study with Sound-Induced Flash Illusions.

The pathophysiological mechanisms underlying migraine are more difficult to investigate in children than in the adult population. Abnormal cortical excitability turns out to be one of the most peculiar aspects of migraine, accounting for the manifestations of migraine attacks. Recently, visual cortical excitability has been explored effectively in adult migraineurs with a technique based on cross-modal audio-visual illusions (with sound-induced flash illusions (SIFIs) being reduced in migraineurs compared to non-migraineur subjects). On such a basis, in this study, we investigated visual cortical excitability in children with migraine using SIFIs using combinations of visual and sound stimuli presented randomly. We evaluated 26 children with migraine without aura and 16 healthy children. Migraineurs did not differ from the age-matched healthy subjects regarding fission or fusion illusions but perceived more flashes in trials of multiple flashes with or without beeps. The higher number of SIFIs in migraineur children compared to adults may be due to a greater propensity of visual stimulation to be driven by auditory stimuli (i.e., acoustic dominance). The increased ability to perceive flashes reveals a hyperfunctional visual cortex, demonstrating that the use of SIFIs is a valid tool for assessing visual cortical responsiveness even in pediatric migraine.

Erenumab and Possible CGRP Effect on Chronotype in Chronic Migraine: A Real-Life Study of 12 Months Treatment.

The introduction of monoclonal antibodies (mAbs) directed against the calcitonin gene-related peptide (CGRP), or its receptor (CGRPr), revolutionized migraine management due to their high efficacy and few side effects. Data suggest that the CGRP may even be implicated in circadian rhythm, but studies about the effect of anti-CGRP treatments on sleep are still lacking. The aim of the present study was to assess the effect of erenumab (70 and 140 mg per month), a human mAb directed against CGRPr, on chronotype in chronic migraineurs; secondly, we assessed its efficacy, safety, and the effects on anxiety and depression. Sleep was evaluated using self-administrable questionnaires investigating chronotype, sleep quality, and daytime sleepiness. Migraine diaries and several self-administrable questionnaires regarding headache impact and psychological correlates were evaluated every 3 months during 12 months of treatment. Eighty-eight patients were included; most of them showed a significant reduction in headache frequency and an improvement in psychological symptoms. Moreover, an initial change in chronotype was observed at the three-month assessment from a morning chronotype to an intermediate one; a similar trend remained in the other evaluations, even if it did not reach a statistical significance. Lastly, patients who responded to the treatment showed a progressive sleep efficiency reduction. The present real-life study hypothesized the influence of erenumab on chronotype, representing a link between circadian rhythm, CGRP, and migraine.

OnabotulinumtoxinA Modulates Visual Cortical Excitability in Chronic Migraine: Effects of 12-Week Treatment.

Chronic migraine is a burdensome disease presenting with episodic pain and several symptoms that may persist even among headache attacks. Multisensory integration is modified in migraine, as assessed by the level of the perception of sound-induced flash illusions, a simple paradigm reflecting changes in cortical excitability which reveals to be altered in migraineurs. OnabotulinumtoxinA is an effective preventive therapy for chronic migraineurs, reducing peripheral and central sensitization, and may influence cortical excitability. Patients affected by chronic migraine who started onabotulinumtoxinA preventive therapy were included. Clinical effects (headache diaries and migraine related questionnaires) were assessed at the beginning of the therapy and after 12 weeks. Contextually, patients underwent the evaluation of multisensory perception by means of the sound-induced flash illusions. OnabotulinumtoxinA showed effectiveness both in migraine prevention and in reducing headache burden. Even one session of therapy was able to restore, at least partially, multisensory processing, as shown by patients' susceptibility to the sound-induced flash illusion. OnabotulinumtoxinA could influence migraineurs cortical excitability concurrently to the beneficial effects in headache prevention.

Medication overuse and drug addiction: a narrative review from addiction perspective.

Chronic headache is particularly prevalent in migraineurs and it can progress to a condition known as medication overuse headache (MOH). MOH is a secondary headache caused by overuse of analgesics or other medications such as triptans to abort acute migraine attacks. The worsening of headache symptoms associated with medication overuse (MO) generally ameliorates following interruption of regular medication use, although the primary headache symptoms remain unaffected. MO patients may also develop certain behaviors such as ritualized drug administration, psychological drug attachment, and withdrawal symptoms that have been suggested to correlate with drug addiction. Although several reviews have been performed on this topic, to the authors best knowledge none of them have examined this topic from the addiction point of view. Therefore, we aimed to identify features in MO and drug addiction that may correlate. We initiate the review by introducing the classes of analgesics and medications that can cause MOH and those with high risk to produce MO. We further compare differences between sensitization resulting from MO and from drug addiction, the neuronal pathways that may be involved, and the genetic susceptibility that may overlap between the two conditions. Finally, ICHD recommendations to treat MOH will be provided herein.

Migraine and Sport in a Physically Active Population of Students: Results of a Cross-Sectional Study.

OBJECTIVE: In this study, we explored the relationship between migraine and sport in a physically active population of students, analyzing the risk of migraine among sporty students. BACKGROUND: The relationship between sport and migraine is controversial; moreover, several studies report on sport as a migraine trigger, but there is evidence that physical activity could have a relevant role in migraine prevention. METHODS: A cross-sectional survey was conducted using the validated ID-migraine questionnaire including specific demo-anthropometric (gender, age, weight, height) and sports variables on a potentially active student population of the University of Palermo. Evaluation in putative migraine subjects of clinical features and disability was explored through the administration of the Italian version of the Migraine Disability Assessment Scale. Statistical analyses were performed using univariate and logistic regression analyses. RESULTS: Three hundred and ninety-three out of 520 students (210 F, mean age: 23.5 ± 0.7 years; 183 M; mean age: 20.5 ± 0.7 years) participated in this study. Migraine screened positive in 102 subjects (26.0%) and its prevalence was significantly higher among females (P < .001). An increased risk of migraine was found in females, and a protective effect of sport on the risk of migraine among females, but not among males. CONCLUSIONS: The role of exercise in migraine is still unclear. This study supports a protective role of sport in migraine reporting a protective effect in females. Further studies are needed to deepen the association between sport and migraine.

Anodal transcranial direct current stimulation and intermittent theta-burst stimulation improve deglutition and swallowing reproducibility in elderly patients with dysphagia.

BACKGROUND: Dysphagia in the elderly, known as presbydysphagia, has become a relevant public health problem in several countries. Swallowing disorders may be a consequence of different neurological disorders (secondary presbydysphagia) or the expression of the aging process itself (primary presbydysphagia). We aimed to test the therapeutic potential of two different non-invasive brain stimulation (NIBS) techniques in subjects with primary or secondary presbydysphagia. METHODS: A blinded randomized controlled trial with crossover design was carried out in 42 patients, randomly assigned to anodal transcranial direct current stimulation (tDCS) or intermittent theta-burst stimulation (TBS) group. Both tDCS and TBS were applied for 5 consecutive days over the right swallowing motor cortex. The swallowing function was assessed before and 1 and 3 months after the stimulation using the Dysphagia Outcome and Severity Scale (DOSS), scored based on clinical assessment and fiberoptic endoscopic evaluation of swallowing. An electrophysiological method was also applied to evaluate changes in the reproducibility of the swallowing behavior. KEY RESULTS: Both real tDCS and TBS had beneficial effects on the swallowing function in patients with primary and secondary presbydysphagia. Anodal tDCS resulted in an improvement of 0.5 points in DOSS at 1-month follow-up (P = .014), whereas intermittent TBS induced an increase of 0.7 and 0.6 points at 1- and 3-month follow-up evaluations, respectively (P = .0001 and P = .005, respectively). Reproducibility of both the oral and pharyngeal phases of swallowing significantly increased at 1-month follow-up. CONCLUSIONS AND INFERENCES: Our results suggest that non-invasive cortical stimulation may be useful for dysphagia recovery in elderly patients.

Intracortical facilitation within the migraine motor cortex depends on the stimulation intensity. A paired-pulse TMS study.

INTRODUCTION: Connectivity within the primary motor cortex can be measured using the paired-pulse transcranial magnetic stimulation (TMS) paradigm. This evaluates the effect of a first conditioning stimulus on the motor evoked potential (MEP) elicited by a second test stimulus when different interstimulus intervals are used. Aim of the present study was to provide, in patients suffering from migraine without aura (MwoA), additional information on intracortical facilitation (ICF), short intracortical inhibition (SICI), and long intracortical inhibition (LICI), using different intensities of the test stimulus (TS). METHODS: We enrolled 24 patients with episodic MwoA and 24 age- and sex-matched healthy volunteers. Both patients and controls were randomly assigned to two different experimental groups: the first group underwent evaluation of ICF, while in the second group we assessed SICI and LICI. All these measures were assessed by using three different suprathreshold intensities of the TS (110%, 130% and 150% of the resting motor threshold, RMT). Interstimulus intervals (ISIs) of 10 ms were used for testing ICF, while SICI and LICI were carried out by using 2 ms and 100 ms ISIs respectively. All migraine patients underwent the experimental protocol while in the interictal pain-free state. RESULTS: A main finding of the study was that an increased ICF could be seen in migraineurs as compared to the healthy subjects only by using a 110% intensity of the TS. Instead, no significant differences were observed between patients and controls as regards both measures of intracortical inhibition. CONCLUSION: We show that hyperresponsivity of the glutamatergic intracortical circuits can be detected in the migraine motor cortex only by applying a low suprathreshold intensity of stimulation. Our results strengthen the notion that, to be reliable, the assessment of cortical excitability in migraine should always include evaluation of the cortical response to different stimulation intensities.

Wernicke-Korsakoff syndrome complicated by subacute beriberi neuropathy in an alcoholic patient.

Thiamine (vitamin B1) deficiency is a common condition in alcohol abusers, which can lead to damage of both the peripheral and the central nervous systems. Here we describe the case of an alcoholic patient who presented with acute onset of ataxia, severe weakness of the four limbs, and hypoesthesia and dysesthesia of the distal portion of the upper and lower extremities. The clinical picture also included mental confusion and amnesia. A diagnosis of Wernicke-Korsakoff syndrome was made based on clinical symptoms and brain RMI findings. Electromyography and electroneurography revealed signs of subacute axonal sensory-motor polyneuropathy that were compatible with a rare acute presentation of beriberi. Patient immediately received parenteral thiamine administration, which resulted in rapid clinical amelioration of ataxia and confusion and also in a significant improvement of motor and sensory deficits. The association between Wernicke-Korsakoff syndrome and acute axonal polyneuropathy is a very rare condition that could make less recognizable the clinical picture of a thiamine deficiency. However, the diagnosis of thiamine deficiency should be suspected in every alcoholic patient presenting with acute onset symptoms of central and/or peripheral nervous system involvement. This because the immediate replacement treatment can be life-saving and reverse the clinical symptoms.

Emergence delirium in children: a comparison of sevoflurane and desflurane anesthesia using the Paediatric Anesthesia Emergence Delirium scale.

OBJECTIVES/AIM: This randomized control trial was designed to evaluate the incidence of emergence delirium (ED) in preschool children receiving sevoflurane or desflurane anesthesia combined with an effective caudal block. BACKGROUND: While ED has been described in children receiving sevoflurane or desflurane anesthesia, a direct comparison between the two agents using a validated ED assessment tool has not been reported previously. METHODS/MATERIALS: Two hundred and sixty preschool children scheduled for elective sub-umbilical surgery were randomized to receive sevoflurane or desflurane anesthesia combined with a caudal block. ED was defined as a Paediatric Anesthesia Emergence Delirium scale (PAED) ≥ 10 points. A delirium-specific score (ED I) was calculated from the first three items of the PAED score (eye contact, purposeful actions, awareness of the surroundings) and a nonspecific score (ED II) from the last two items on the PAED score (restlessness and inconsolability) to test the hypothesis that some items of the PAED scale may better reflect clinical ED than others. RESULTS: Thirty-one (25%) children in each group demonstrated ED after awakening with ED being of shorter duration in the desflurane group than the sevoflurane group. An ED I score of nine points had a sensitivity of 0.93 and a specificity of 0.94 for ED. An ED II score of five points had a sensitivity of 0.34 and specificity of 0.95 for ED. CONCLUSION: Sevoflurane and desflurane anesthesia were associated with similar incidences of ED in children undergoing sub-umbilical surgery and receiving effective regional anesthesia. High scores on the first three items of the PAED scale were highly correlated with ED. The items restlessness and inconsolability had lower sensitivity for the diagnosis of ED.