Background: Recent randomized trials have questioned the benefit of endovascular therapy (EVT) for medium vessel occlusion (MeVO) stroke, but data from clinical practice are limited. This study aimed to assess the effectiveness and safety of EVT, with or without intravenous thrombolysis (IVT), versus IVT alone in MeVO stroke using registry-based real-world data. Methods: This retrospective multicenter study included patients from 76 Italian centers in the SITS registry (January 2020-December 2023). Adults with acute ischemic stroke due to MeVO (ACA A1/A2, MCA M2/M3 or more distal, or PCA P1/P2), treated with IVT or EVT±IVT, and with available 90-day modified Rankin Scale (mRS) scores were included. Patients with tandem occlusions were excluded. Propensity score matching (1:1) was used to balance baseline variables. Primary outcome was functional independence (mRS 0-2) at 90 days. Secondary outcomes included in-hospital mortality, intracranial hemorrhage incidence, and recanalization status. Results: Among 1375 total patients, 780 were included and matched (390 per group) by propensity score. Baseline characteristics were balanced. Functional independence at 90 days was achieved in 57.7% of EVT±IVT patients versus 59.2% in the IVT-only group (OR 0.939, 95% CI 0.706-1.248, p=0.663). In-hospital mortality was non significantly lower in the EVT±IVT group (5.4% vs 8.7%, p=0.069). Symptomatic intracranial hemorrhage rates were comparable between groups, although overall hemorrhagic complications were higher with EVT (18.4% vs 11.2%, p<0.0001). Successful recanalization occurred in 81.0% of EVT cases. Stratified analyses by stroke severity and treatment timing showed consistent lack of benefit across all subgroups (all interaction p-values >0.05). Conclusions: EVT did not improve long-term functional outcomes compared to IVT alone in MeVO stroke but was associated with higher hemorrhagic risk. These findings support a cautious approach to EVT in this setting, in line with recent trial evidence. ### Competing Interest Statement AZ declares consulting and speaker fees from Bayer, Boehringer-Ingelheim, Alexion, Daiichi Sankyo, Pfizer, PIAM, Amgen, fees for Advisory Board from Boehringer-Ingelheim, Daiichi Sankyo, Bayer and Astra Zeneca, not related to this study. ### Funding Statement This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The coordinating center (Fondazione IRCCS San Gerardo dei Tintori, Monza) determined that this study is exempt from full review as it involves secondary analysis of de-identified data from the SITS registry. Participating sites confirmed that no additional local approval was required for use of de-identified registry data, per local regulations. Informed consent was [waived/not required] due to use of de-identified data. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data are available from the SITS registry but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the SITS registry.

Introduction: Growing evidence has been published as to the impact of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) on cerebrovascular events over the last few months, with considerable attention paid to ischemic strokes. Conversely, little is known about the clinical course of intracerebral haemorrhage (ICH) and simultaneous SARS-CoV-2 infection. Method: The Italian Society of Hospital Neurosciences (SNO) promoted a multicentre, retrospective, observational study (SNO-COVID-19), involving 20 Neurological Departments in Northern Italy. Clinical data on patients with acute cerebrovascular diseases, admitted from March 1st to April 30th, 2020, were collected. A comparison was made of the demographical and clinical features of both SARS-CoV-2 positive and negative patients with ICH. Results: 949 patients were enrolled (average age 73.4 years; 52.7% males); 135 patients had haemorrhagic stroke and 127 (13.4%) had a primary ICH. Only 16 patients with ICH (12.6%) had laboratory confirmed SARS-CoV-2 infection, both symptomatic and asymptomatic. SARS-CoV-2 related pneumonia or respiratory distress (OR 5.4), lobar location (OR 5.0) and previous antiplatelet or anticoagulant treatment (OR 2.9) were the only factors significantly associated with increased mortality in ICH. SARS-CoV-2 infection, regardless of respiratory involvement, led to a non-significantly increased risk of in-hospital death (37.5% vs 23.4%, p = 0.2). Discussion: ICH patients with COVID-19 did not experience an increase in mortality as striking as ischemic stroke. The inflammatory response and respiratory complications could justify the slight increase of death in ICH. Bleeding sites and previous antiplatelet or anticoagulant treatment were the only other predictors of a worse outcome.

Background: We aimed to investigate if the carotid intima-media thickness (IMT) at baseline and the HAD2S score, composed of the sum of single risk factors (hypertension, age ≥ 75 years, diabetes, dyslipidemia, smoking), were predictive of plaque progression. Methods: We performed a retrospective analysis on real-life prospectively collected data from patients with any detectable carotid plaque at follow up. The plaque score, calculated at baseline (T0) and at a median follow up of 36.6 months (IQR 39.6–34.3) (T3), was defined as 0: no plaque or stenosis < 30%; 1: stenosis in the range 30–49%; 2: in the range 50–69%; 3: in the range 70–99% and 4: occlusion. Carotid IMT was measured at T0 and T3; HAD2S score was calculated at baseline. Results: We included 340 patients with a mean age of 69.9 (9.1) years and 25.3% subjects had plaque progression. Individuals with progression had a median HAD2S score of 3 (1) while those without progression had 2 (1). Patients with progression had a mean baseline IMT of 0.86 (0.17) while those without progression had 0.77 (0.18) (p < 0.0001). A correlation between progression and baseline IMT was found (p = 0.002). Conclusion: Baseline IMT could be considered a predictor of progression. Patients with progression had an HAD2S score higher than those without evolution.

OBJECTIVE:We compared outcomes after treatment with direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and a recent cerebral ischemia. METHODS:We conducted an individual patient data analysis of seven prospective cohort studies. We included patients with AF and a recent cerebral ischemia (<3 months before starting oral anticoagulation) and a minimum follow-up of 3 months. We analyzed the association between type of anticoagulation (DOAC versus VKA) with the composite primary endpoint (recurrent ischemic stroke [AIS], intracerebral hemorrhage [ICH], or mortality) using mixed-effects Cox proportional hazards regression models; we calculated adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs). RESULTS:We included 4,912 patients (median age, 78 years [interquartile range {IQR}, 71-84]; 2,331 [47.5%] women; median National Institute of Health Stroke Severity Scale at onset, 5 [IQR, 2-12]); 2,256 (45.9%) patients received VKAs and 2,656 (54.1%) DOACs. Median time from index event to starting oral anticoagulation was 5 days (IQR, 2-14) for VKAs and 5 days (IQR, 2-11) for DOACs (p = 0.53). There were 262 acute ischemic strokes (AISs; 4.4%/year), 71 intracranial hemorrrhages (ICHs; 1.2%/year), and 439 deaths (7.4%/year) during the total follow-up of 5,970 patient-years. Compared to VKAs, DOAC treatment was associated with reduced risks of the composite endpoint (HR, 0.82; 95% CI, 0.67-1.00; p = 0.05) and ICH (HR, 0.42; 95% CI, 0.24-0.71; p < 0.01); we found no differences for the risk of recurrent AIS (HR, 0.91; 95% CI, 0.70-1.19; p = 0.5) and mortality (HR, 0.83; 95% CI, 0.68-1.03; p = 0.09). INTERPRETATION:DOAC treatment commenced early after recent cerebral ischemia related to AF was associated with reduced risk of poor clinical outcomes compared to VKA, mainly attributed to lower risks of ICH. ANN NEUROL 2019;85:823-834.

PURPOSE OF REVIEW:The absolute risk of pregnancy-associated intracranial haemorrhage (ICH) has been reported to be relatively low and often associated with high risks of life-long disabilities and mortality. The aim of this narrative review was obtaining a better understanding of the current management practices for ICH, unruptured aneurysms and/or arteriovenous malformations during pregnancy, as well as the effects of future pregnancies, and the uses of oral contraceptive or HRT.RECENT FINDING:General guidelines for the management of ICH are used for pregnant women but additional expedient and thorough evaluation of foetal viability and its gestational age are requested. Recent epidemiological data suggest that menopause can be an independent risk factor for the development of aneurysmal subarachnoid haemorrhage. Furthermore, several population-based studies performed on women with aneurysmal subarachnoid haemorrhage observed a lower risk of bleeding with HRT.SUMMARY:The current review observed that the management practices for ICH during pregnancy were seen to be somewhat uniform. Whereas, the practices regarding future pregnancies and the prescriptions of either oral contraceptives or HRT do not follow coherent patterns. In light of this, we recommend the establishment of an international registry that would collect data on women with ICH during pregnancy.

Background and Purpose- Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods- We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results- Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P<0.0001), as well as ischemic (odds ratio, 2.2; 95% CI, 1.3-3.9; P=0.005) and hemorrhagic (odds ratio, 2.4; 95% CI, 1.2-4.9; P=0.01) end points separately. Conclusions- Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.

Background In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation (HT). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT, (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT. Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3–8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0–6.0) of those without HT; 53.1% of patients with HT were deceased or disabled compared with 35.8% of those without HT. On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24–2.35). Conclusions In patients with HT, anticoagulation was initiated about 12 days later than patients without HT. This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability.

BackgroundTIA has been recently re-defined as a transient episode of neurological dysfunction caused by ischemia without acute infarction. The gold standard to exclude the presence of ischemic lesions is acute brain MR. However, in many clinical settings, the 24/7 availability of MR is, at best, irregular. Being so, an appropriate adoption of this definition, which excludes the presence of ischemic lesions, can only be equally irregular. Our aim was to retrospectively compare the long-term outcomes of patients receiving acute care for TIA diagnosed with the new, tissue-based definition, and those diagnosed only on symptom duration.MethodsWe analyzed 480 patients (227 males) from two centers: group 1 consisted of 162 patients with time-defined TIA; group 2 of 315 patients with negative brain DW-MRI (tissue-based TIAs). We considered the combined recurrence of TIA, stroke, myocardial infarction, and angina as endpoints.ResultsBoth groups had a similar mean follow-up duration (38.3months vs. 37.2months) and were comparable for vascular risk factors, clinical features, and etiology. The combined endpoint rates were 11.1% for both groups, and the rates for segregate endpoints did not differ between groups. Recurrence was correlated with atrial fibrillation, diabetes, and high diastolic blood pressure.ConclusionsThe long-term outcomes of TIA patients did not differ according to the definitions applied. Therein suggesting that, even without acute MRI results, a clinical diagnosis seemed to be enough to assure prompt medical treatment and similar long-term outcomes.

The personal and bibliographical histories of the two Russian writers, Leo Nikolaevich Tolstoy and Ivan Sergeevich Turgenev, are strictly connected to social and scientific developments in nineteenth century Russia. In particular, in the field of medicine and of neurology, these two authors had personal issues and interests, kindled by Russia's opening to Western European thought. Neurology at the beginning of the nineteenth century was not developed in Russia, and in the second half of the century the new generation of neurologists trained abroad, in particular in France, where Charcot was an eminent figure who also travelled to Russia to help establish the new "Russian neurology." The following generation of neuropsychiatrists, in turn, looked upon Russian writers, and in particular Tolstoy, as models of psychopathology both for their personal biography and for character depictions. Tolstoy experienced depression, which he overcame after a religious/philosophical conversion; his renewed views were expressed in his later works, and led to the coining of the term "Tolstoyism" in medical literature. Turgenev admired the works by Tolstoy, but his vision was more pragmatic and close to those of his European colleagues of the time. His best effort was in the description of physical illnesses, and this was recognized by physicians and psychiatrists reading and commenting on his works.

Daith piercing is an ear piercing located at the crus of the helix, bilaterally. It is getting great consent on social media as alternative treatment in chronic migraine. No data about its efficacy and action are available in scientific literature so far. We present the case of a 54-year-old male patient suffering from refractory chronic migraine with medication-overuse, who substantially improved after bilateral ear daith piercing. His migraine was refractory to symptomatic as well as prophylactic therapies. He used to treat headaches with up to five symptomatic drugs per attack and had attempted several pharmacological preventive therapies, including Onabotulinumtoxin A. He also underwent detoxification treatments with intravenous steroids and diazepam, without durable benefit. At the time of daith piercing, the headache-related disability measures showed a HIT-6 score of 64, a MIDAS-score of 70, and a 11-point Box scale of 5. On his own free will, he decided to get a "daith piercing." After that, he experienced a reduction of migraine attacks, which became very rare, and infrequent, less disabling episodes of tension-type headache (HIT-6 score of 56; MIDAS score of 27, 11-point Box scale of 3). Painkiller assumption has much decreased: he takes only one tablet of indomethacin 50 mg to treat tensive headaches, about four times per month. Beyond a placebo effect, we can speculate a vagal modulation as the action mechanism of daith piercing: a nociceptive sensory stimulus applied to trigeminal and vagal areas of the ear can activate ear vagal afferents, which can modulate pain pathways by means of projections to the caudal trigeminal nucleus, to the locus coeruleus and to the nucleus raphe magnus. Currently, daith piercing cannot be recommended as migraine treatment because of the lack of scientific evidence, the unquantified rate of failure and the associated risks with insertion. However, given the increasing but anecdotal evidence, we think that the mechanism needs testing by means of a controlled clinical trial in a population of chronic migraineurs.

Background: White matter hyperintensities (WMH) are a common finding in aged individuals affected by carotid artery disease and are a risk factor for first-ever and recurrent stroke. We investigated if white matter damage increases the risk of brain microembolism during carotid artery stenting (CAS), as evaluated by the appearance of new areas of restricted diffusion on diffusion-weighted images (DWI). Methods: We evaluated 47 patients with severe internal carotid artery (ICA) stenosis undergoing CAS, comparing preprocedural clinical, ultrasound and radiological characteristics. WMH volume was computed on FLAIR images before CAS. After CAS, the DWI scan was looked over for areas of restricted diffusion (DWI lesions). A first univariate analysis was adopted to compare groups according to the occurrence of DWI lesions. Then, the variable DWI lesion was modelled by means of a logistic regression model. Results: Seventeen patients developed at least 1 DWI lesion after CAS. Compared with non-DWI, DWI patients were more commonly treated in the left ICA (p = 0.007) and had a more severe WMH damage (p = 0.027). Indeed, the risk of a DWI lesion was higher in left versus right stenosis (OR = 9.0, 95% CI 1.9-42.7, p = 0.005) and increased for each log-unit of WMH lesion load (OR = 7.05, 95% CI 1.07-46.49, p = 0.042). A WMH lesion load of at least 5.25 cm3 had a 50% probability of occurrence of a new DWI lesion. Conclusions: Treated side and preexisting white matter damage are risk conditions for brain microembolism during CAS. This should be taken into account to optimize severe carotid artery disease management.

In the recent years, classical vascular risk factors have been suggested to play a role also in the development of degenerative dementia. Arterial hypertension has been implicated in the pathogenesis of dementia but no conclusive results have been produced yet; more recently, blood pressure variability (BPV) has been suggested as a more important risk factor for both silent brain vascular lesions and the development of dementia. Blood pressure variability is defined as the variation in blood pressure over time, measured on different time spans and in different ways. We reviewed current scientific literature about the role of BPV in the pathogenesis of dementia, and about the association of abnormal BPV patterns and different forms of dementia. We also suggested some hypothetical pathogenic mechanisms.

Medication-overuse headache (MOH) is a secondary chronic headache developing as a consequence of prolonged overuse of symptomatic headache drugs for at least 3 consecutive months. It usually, but not invariably, resolves after the overuse is discontinued[1]. Benefit of acute withdrawal of the overused medication has been shown to be effective[2]; performing a transitional therapy (“bridge therapy”) during the days of withdrawal may ensure symptomatic relief from rebound headache and avoid withdrawal symptoms. In this setting, i.v. methylprednisolone may have a protective role[3].

Different strategies of neurostimulation have been developed as treatment tools for migraine. Among them, vagus nerve stimulation (VNS) can be performed both invasively and non-invasively. Recently, “Gammacore” has been approved as a non-pharmacological and non-invasive tool for headache, and a recent study demonstrated its efficacy in 22% of patients with acute migraine attacks[1]. Although the pathophysiology of migraine is not yet fully understood, many studies have shown a role of sterile inflammation of cerebral vessels and of the change in diameter of the intracranial arteries. Blood flow velocities and vasomotor reactivity (VMR) in patients suffering from migraine without aura in the intercritical phase were found either increased or normal compared to non-migraineurs healthy controls[2, 3]. Since the vagus nerve is the largest parasympathetic nerve of the body, it is probable that its neuromodulation can affect cerebral hemodynamics. The purpose of the study was to evaluate the effects of external vagus nerve stimulation on VMR of patients suffering from chronic migraine.

Neurodegeneration with Brain Iron Accumulation (NBIA) syndromes are inherited disorders that lead to impaired iron metabolism with consequent cerebral and/or systemic metal overload. Pathological brain iron deposition usually results in neurological dysfunction characterized by movement disorders and cognitive impairment [ [1] Schneider S.A. Dusek P. Hardy J. Westenberger A. Jankovic J. Bhatia K.P. Genetics and pathophysiology of neurodegeneration with brain iron accumulation (NBIA). Curr Neuroph. 2013; 11: 59-79 Crossref PubMed Scopus (114) Google Scholar ]. We report here a case of NBIA with aceruloplasminemia (ACP) and a novel mutation and clinical phenotype. A 51-year-old Caucasian woman was referred to our Neurology Unit with the subtle and progressive onset of involuntary movements, unsteady gait, cognitive deterioration and behavioral changes. Her previous medical history included microcytic anemia, type-1 diabetes and retinopathy. She was born to non-consanguineous parents and there was no family history of neurological diseases. The pattern of movement disturbances was compatible with acathisia, oro-facial dyskinesias, limb choreo-dystonia and cerebellar ataxia. Neuropsychological evaluation revealed executive dysfunctions. We performed an extensive work-up in order to rule out causes of secondary hyperkinetic disorder with dementia. Clinical biochemistry, autoimmune and hematological screenings were normal apart from microcytic anemia (hemoglobin 10.4 g/dL, mean cellular volume 67 fl) and changes in the serum metal indexes: copper (1.75 μmol/L) and iron (3.4 μmol/L) were below the reference range and ceruloplasmin (Cp) was undetectable as Cp concentration or as o-dianisidine Cp enzymatic activity [ [2] Siotto M. Pasqualetti P. Marano M. Squitti R. Automation of o-dianisidine assay for ceruloplasmin activity analyses: usefulness of investigation in Wilson's disease and in hepatic encephalopathy. J Neural Transm. 2014; 121: 1281-1286 Crossref PubMed Scopus (33) Google Scholar ]. Serum ferritin (85 ng/mL) and transferrin (2.6 g/dL) were within the normal range while transferrin saturation was very low (5%). A brain magnetic resonance imaging (MRI) was performed, and mineral sensitive sequences revealed a massive extrapallidal deposition of ferromagnetic substances (Fig. 1). Therefore, molecular tests were performed. Due to the absence of serum Cp and the presence of massive brain iron accumulation, we used polymerase chain reaction (PCR) based assays to look for coding regions and intron-exon boundaries of the CP gene on chromosome 3q coding for Cp. Amplifications of exon 12 gave no signal suggesting a homozygous deletion of the entire exon. No other mutation was observed by the CP sequencing. Huntington and Wilson's diseases were excluded by a PCR analysis for trinucleotide expansion mutation of huntingtin gene on chromosome 4p and for mutations of ATP7B gene on chromosome 13q respectively. Finally, an ancillary MRI with metal sensitive sequences was performed to determine liver iron, but no signs of metal overload were observed. Hyperkinesias were successfully treated with tetrabenazine (12.5 mgs, t.i.d), with a concurrent mild improvement in behavioral symptoms.

Global postural rehabilitation (GPR) is a method of physical therapy, designed by Professor Souchard, for the treatment of osteo-neuro-muscular pathologies. The correction of oculo-motor, cranio-cervical and temporo-mandibular joint dysfunctions inside “postural globality” can lead to the elimination of muscle tension that is one of the most important triggers and, at the same time, complications of headaches. The present study aimed at evaluating whether this method could be useful in reducing the number, intensity and duration of attacks and also the use of painkillers in patients with migraine without aura.

A relatively new approach to brain function in neuroscience is the "functional connectivity", namely the synchrony in time of activity in anatomically-distinct but functionally-collaborating brain regions. On the other hand, diffusion tensor imaging (DTI) is a recently developed magnetic resonance imaging (MRI)-based technique with the capability to detect brain structural connection with fractional anisotropy (FA) identification. FA decrease has been observed in the corpus callosum of subjects with Alzheimer's disease (AD) and mild cognitive impairment (MCI, an AD prodromal stage). Corpus callosum splenium DTI abnormalities are thought to be associated with functional disconnections among cortical areas. This study aimed to investigate possible correlations between structural damage, measured by MRI-DTI, and functional abnormalities of brain integration, measured by characteristic path length detected in resting state EEG source activity (40 participants: 9 healthy controls, 10 MCI, 10 mild AD, 11 moderate AD). For each subject, undirected and weighted brain network was built to evaluate graph core measures. eLORETA lagged linear connectivity values were used as weight of the edges of the network. Results showed that callosal FA reduction is associated to a loss of brain interhemispheric functional connectivity characterized by increased delta and decreased alpha path length. These findings suggest that "global" (average network shortest path length representing an index of how efficient is the information transfer between two parts of the network) functional measure can reflect the reduction of fiber connecting the two hemispheres as revealed by DTI analysis and also anticipate in time this structural loss.

Background OnabotulinumtoxinA injection according to PREEMPT protocol is a second-line therapy for chronic migraine (CM)[1]. While its efficacy on frequency of headache has been demonstrated[2], our current clinical experience indicates that patients report benefits regardless of reduction of frequency of attacks, as Lipton et al previously showed[3]. The present study aimed at assessing the impact of botulin injection on intensity, quality and perception of pain in patients with CM.