Neuroimaging markers of Alice in Wonderland syndrome in patients with migraine with aura.

Background: The Alice in Wonderland syndrome (AIWS) is a transient neurological disturbance characterized by sensory distortions most frequently associated with migraine in adults. Some lines of evidence suggest that AIWS and migraine might share common pathophysiological mechanisms, therefore we set out to investigate the common and distinct neurophysiological alterations associated with these conditions in migraineurs. Methods: We conducted a case-control study acquiring resting-state fMRI data from 12 migraine patients with AIWS, 12 patients with migraine with typical aura (MA) and 24 age-matched healthy controls (HC). We then compared the interictal thalamic seed-to-voxel and ROI-to-ROI cortico-cortical resting-state functional connectivity between the 3 groups. Results: We found a common pattern of altered thalamic connectivity in MA and AIWS, compared to HC, with more profound and diffuse alterations observed in AIWS. The ROI-to-ROI functional connectivity analysis highlighted an increased connectivity between a lateral occipital region corresponding to area V3 and the posterior part of the superior temporal sulcus (STS) in AIWS, compared to both MA and HC. Conclusion: The posterior STS is a multisensory integration area, while area V3 is considered the starting point of the cortical spreading depression (CSD), the neural correlate of migraine aura. This interictal hyperconnectivity might increase the probability of the CSD to directly diffuse to the posterior STS or deactivating it, causing the AIWS symptoms during the ictal phase. Taken together, these results suggest that AIWS in migraineurs might be a form of complex migraine aura, characterized by the involvement of associative and multisensory integration areas.

Functional connectivity alterations in migraineurs with Alice in Wonderland syndrome.

BACKGROUND AND PURPOSE: Alice in Wonderland syndrome (AIWS) is a neurological disorder characterized by erroneous perception of the body schema or surrounding space. Migraine is the primary cause of AIWS in adults. The pathophysiology of AIWS is largely unknown, especially regarding functional abnormalities. In this study, we compared resting-state functional connectivity (FC) of migraine patients experiencing AIWS, migraine patients with typical aura (MA) and healthy controls (HCs). METHODS: Twelve AIWS, 12 MA, and 24 HCs were enrolled and underwent 3 T MRI scanning. Independent component analysis was used to identify RSNs thought to be relevant for AIWS: visual, salience, basal ganglia, default mode, and executive control networks. Dual regression technique was used to detect between-group differences in RSNs. Finally, AIWS-specific FC alterations were correlated with clinical measures. RESULTS: With respect to HCs, AIWS and MA patients both showed significantly lower (p < 0.05, FDR corrected) FC in lateral and medial visual networks and higher FC in salience and default mode networks. AIWS patients alone showed higher FC in basal ganglia and executive control networks than HCs. When directly compared, AIWS patients showed lower FC in visual networks and higher FC in all other investigated RSNs than MA patients. Lastly, AIWS-specific FC alterations in the executive control network positively correlated with migraine frequency. CONCLUSIONS: AIWS and MA patients showed similar FC alterations in several RSNs, although to a different extent, suggesting common pathophysiological underpinnings. However, AIWS patients showed additional FC alterations, likely due to the complexity of AIWS symptoms involving high-order associative cortical areas.

A Propensity Score Matching Study on the Effect of OnabotulinumtoxinA Alone versus Short-Term Psychodynamic Psychotherapy Plus Drug-of-Choice as Preventive Therapy in Chronic Migraine: Effects and Predictive Factors.

OBJECTIVE: The objective of this study was to test the superiority of multidisciplinary approach, that is, Short-Term Psychodynamic Psychotherapy (STPP) plus drug of choice, versus monotherapy, that is, OnabotulinumtoxinA (OnaBoNT-A). METHOD: We consecutively recorded data from chronic migraine (CM) patients, with or without medication overuse headache (MOH), who underwent STPP or OnaBoNT-A, with a 3-month follow-up schedule. Headache days and analgesics intake were monitored as primary outcome measures. Propensity score matching (PSM) was used to eliminate discrepancies between groups. Discriminant function analysis (DFA) was used to pinpoint predictive factors associated with the clinical response. RESULTS: 96 patients with CM (64% with MOH) were treated with STPP and 54 (59% with MOH) with OnaBoNT-A. At baseline, OnaBoNT-A patients had more failed preventive therapies, more years of illness and chronicity, and were older; STPP patients were more depressed and had a higher HIT-6. Both STPP and OnaBoNT-A patients showed a significant reduction of headache days (STPP: -14 vs. OnaBoNT-A:-14.3) and analgesics intake (STPP: -12,3 vs. OnaBoNT-A -13.5 pills/month), respectively. MOH diminished more in STPP, adherence was higher in OnaBoNT-A. Results were confirmed after PSM balancing of the groups for those variables that resulted as different (but age). CONCLUSION: OnaBoNT-A monotherapy produced similar results to psychotherapy plus medication, after correcting for baseline differences.

Prevalence and characteristics of Alice in Wonderland Syndrome in adult migraineurs: Perspectives from a tertiary referral headache unit.

BACKGROUND: Migraine affects how the brain processes sensory information at multiple levels. The aberrant integration of visual and somatosensory stimuli is thought to underlie Alice in Wonderland Syndrome, a disorder often reported as being associated with migraine. However, there is still a lack of knowledge about the epidemiology of this syndrome in migraineurs and the association between Alice in Wonderland Syndrome episodes and migraine attacks. Therefore, we conducted a prospective cohort study to systematically evaluate the prevalence and the clinical features of Alice in Wonderland Syndrome in a large sample of patients with migraine. METHODS: All the patients attending for the first time a tertiary-level headache clinic were consecutively screened for Alice in Wonderland Syndrome symptoms by means of an ad hoc questionnaire and detailed clinical interview, over a period of 1.5 years. Patients experiencing Alice in Wonderland Syndrome symptoms were contacted for a follow-up after 8-12 months. RESULTS: Two hundred and ten patients were recruited: 40 patients (19%) reported lifetime occurrence of Alice in Wonderland Syndrome, 90% of whom (38/40) had migraine with aura. Thirty-one patients experienced episodes of Alice in Wonderland Syndrome within 1 h from the start of migraine headache. Patients reported either visual or visual and somatosensory symptoms (i.e. somatosensory symptoms never presented alone). We collected the follow-up details of 30 patients with Alice in Wonderland Syndrome, 18 of whom had been prescribed a preventive treatment for migraine. After 8-12 months, 5 of the treated patients reported a decrease, while 13 reported no episodes of Alice in Wonderland Syndrome. CONCLUSION: Alice in Wonderland Syndrome prevalence in migraineurs was found to be higher than expected. Alice in Wonderland Syndrome was mostly associated with migraine with aura and tended to occur close to the migraine attack, suggesting the existence of a common pathophysiological mechanism. Patients treated with migraine preventive treatments had a higher chance of decreasing or even resolving Alice in Wonderland Syndrome episodes.

Corrigendum: A Case of Post-traumatic Persistent Nasal Pain.

[This corrects the article DOI: 10.3389/fneur.2019.01409.].

Understanding the nature of psychiatric comorbidity in migraine: a systematic review focused on interactions and treatment implications.

BACKGROUND: Migraine is a highly prevalent and disabling neurological disorder which is commonly linked with a broad range of psychiatric comorbidities, especially among subjects with migraine with aura or chronic migraine. Defining the exact nature of the association between migraine and psychiatric disorders and bringing out the pathophysiological mechanisms underlying the comorbidity with psychiatric conditions are relevant issues in the clinical practice. METHODS: A systematic review of the most relevant studies about migraine and psychiatric comorbidity was performed using "PubMed", "Scopus", and "ScienceDirect" electronic databases from 1 January 1998 to 15 July 2018. Overall, 178 studies met our inclusion criteria and were included in the current review. RESULTS: According to the most relevant findings of our overview, the associations with psychiatric comorbidities are complex, with a bidirectional association of major depression and panic disorder with migraine. Importantly, optimizing the pharmacological and non-pharmacological treatment of either migraine or its psychiatric comorbidities might help clinicians to attenuate the burden of both these conditions. CONCLUSIONS: The available data highlight the need for a comprehensive evaluation of psychiatric disorders in migraine in order to promote an integrated model of care and carefully address the burden and psychosocial impairment related to psychiatric comorbidities in migraine.

A Case of Post-traumatic Persistent Nasal Pain.

Nasal pain is a complex and misdiagnosed entity with various peripheral and central etiologies. It is often a bothersome, treatment-resistant condition and could be spontaneous or post-traumatic. Although pain usually occurs immediately after injury, rarely it may occur long after the nasal trauma. Due to its rarity, successful treatment is difficult because of the lack of standardized options. According to our experience, an effective therapeutic approach should take into account both local inflammatory factors and aberrant nerve modulations. We describe the case of a young woman complaining of a delayed onset persistent nasal pain occurring 1 month after facial trauma and who has improved with the addition of intranasal steroids to first-line neuropathic pain treatment.