Background and Aims:

There is an urgent need for sufficiently sensitive, specific and routine biomarkers for glioma, tumour of glial cells.

The main purpose of this study was to identify possible biomarkers in glioma comparing some routine coagulation factors and Neutrophil-to-lymphocyte ratio (NLR) among the following subgroups: a) glioma and MS patients, controls; b) non-recurrent and recurrent glioma patients. As a secondary endpoint we assessed if these markers could be predictive of overall (OS) and progression-free survival (PFS) in glioma patients.

Methods:

This is a single-center, 10-year retrospective study. We evaluated d-dimer, fibrinogen, Antithrombin III (ATIII), Factor VIII (FVIII) and NLR in 138 glioma patients and, for comparison, in 56 multiple sclerosis (MS) patients and 23 healthy controls.

Results:

NLR, d-dimer, ATIII and FVIII were significantly higher in glioma compared to both MS and controls (p<0.0001 for all). ROC curves confirmed that either NLR, ATIII or FVIII were moderately accurate biomarkers (0.7<AUC<0.9) for glioma compared to other two groups. In multivariable analysis, NLR ≥4.3 (median) (HR 1.53 [95%CI 1.04-2.26], p=0.03) together with Karnofsky Performance Status (KPS) ≥80 (median) (0.46 [0.31-0.69], p<0.0001) and use of steroids (1.75 [1.19-2.57], p=0.004) resulted independent predictors of OS while only KPS was independently associated with PFS.

Conclusions:

Our study showed increased levels of either NLR, ATIII, FVIII, or d-dimer in glioma patients compared to MS patients and controls, with the first three representing moderately accurate biomarkers for this cancer. Among these markers, only NLR was found to be predictive for overall survival together with a disability severity and steroid therapy.

Background and Aims:

To assess magnetic resonance imaging (MRI) alterations occurring in patients with trigeminal neuralgia and to explore the predictive ability of MRI for initial radiosurgical outcome and long-term pain relief/recurrence after Gamma Knife radiosurgery (GKSRS).

Methods:

Thirty patients with idiopathic or classical TN, who underwent GKSRS and were followed for at least 24 months, were retrospectively included. Pre-treatment structural MRI and pre- and serial, post-operative clinical features were investigated. Fifteen age- and sex-matched healthy controls were also enrolled. Cortical thickness and gray matter (GM) volumes were assessed in TN patients relative to controls, as well as between patient subgroups according to treatment outcomes (initial responders/non-responders, patients with pain recurrence/long-lasting pain relief at the last follow-up). Clinical and MRI predictors of treatment outcomes were explored.

Results:

Cortical thinning of temporal, prefrontal, cingulate, somatosensory and occipital areas bilaterally was found in TN patients relative to controls. Patients who experienced TN recurrence after initial pain relief were characterized by thicker parahippocampal and temporal cortices bilaterally and greater volume of right amygdala and hippocampus compared to patients with long-lasting pain relief. In TN patients, disease duration and baseline cortical thinning of right parahippocampal, left fusiform and middle temporal cortices were associated with poor outcome after GKSRS at the last follow-up (R²=0.57, p<0.001).

Conclusions:

The study provides novel insights into structural brain alterations of TN patients, which might contribute to disease development and pain maintenance.

Background and Aims:

Neuropathic pain and small-fibers related symptoms have been poorly studied in late-onset TTR-FAP patients, though small-fibre damage is traditionally considered a diagnostic disease clue. Our study aims at assessing neuropathic pain and small fiber-related symptoms in TTR-FAP, besides correlations with specific neurophysiological and skin biopsy findings.

Methods:

We enrolled 21 TTR-FAP patients and 11 asymptomatic TTR mutations carriers. Each individual underwent clinical examination, DN4, NPSI, SFN-SIQ questionnaires, nerve conduction study, Quantitative sensory testing (QST) and skin biopsy. PGP9.5 intraepidermal (IENFD) and piloerector muscle (PMNFD) nerve fiber density was assessed from distal skin samples, along with semi-quantitative evaluation of sweat gland innervation (GNFD). Skin biopsy variables were compared with those from 20 healthy subjects.

Results:

81% patients and 64% carriers showed IENFD, PMNFD and GNFD reduction (p=<0.01), respect to healthy subjects. 71% patients and no carrier presented neuropathic pain, being pins and needles and burning pain the most frequently reported. 50% of patients complained of orthostatic intolerance, palpitations, gastro-intestinal and urinary disturbances and xerostomia, whereas 40% of carriers complained of orthostatic intolerance. Neuropathic pain and small fiber-related symptoms questionnaires scores correlated with distal IENFD, PMNFD, GNFD, QST variables and sural SAP impairment. All neurophysiological and skin biopsy variables negatively correlated with disease stage and duration.

Conclusions:

TTR-FAP patients frequently report neuropathic pain, with higher ratings in advanced disease stages, whereas autonomic dysfunction is less frequently complained. However, since asymptomatic disease stages, a similar small sensory and autonomic fibers involvement is detected by skin biopsy.

Background and Aims:

Merging of sensory information is an important process for all species. Both in humans and in animal models, co-application of bi-modal stimulations results in greater neural activation than the sum of each unimodal stimuli delivered independently. We have tested how the same process of multisensory integration take place in migraine patients, by evaluating the potential ability of concurrent visual and somatosensory stimulations to affect the mechanisms of habituation, an indirect hallmark of cortical responsivity.

Methods:

We recorded somatosensory evoked potentials (SSEPs) in twenty healthy volunteers and in twenty-one migraine patients before, during, and after simultaneous visual stimulation with a black-and-white checkerboard pattern-reversal. Six-hundred sweeps were acquired for each condition and partitioned off-line in 2 blocks of 100 sweeps for the calculation of habituation as the slope of the regression line between the 1^st and the 2^nd block of averaged N20-P25 SSEP amplitude response.

Results:

In both groups the visuo-somesthetic stimulation changed the SSEP N20-P25 habituation seen at baseline. In healthy subjects the concurrent stimulation provoked a loss of habituation (amplitude increment). In migraine patients, who had a deficient habituation at baseline, the simultaneous stimulation produced an amplitude decrement between 1st and 2nd block (habituation).

Conclusions:

There is ample scientific evidence which sustain that migraine patients have an atypical way of processing unimodal information. Our result suggests that also the multisensory integration is affected, and this process could influence the migraine cycle modifying habituation and cortical responsivity, which may lower the migraine threshold and might trigger an attack.

Background and Aims:

Migraine is a common denominator of human experience, likely to be encountered at either first or second hand by many within population. Migraine has a particular impact on young people, a group that is prone to influence by media and popular culture. So is not surprising that artists have on occasion used such condition as a source material for elaboration in their narratives. In this study we aimed at reaching a better understanding of the ways in which migraine is portrayed in popular music, comparing song texts released in the last 30 years.

Methods:

Online music sites were searched for popular songs with the word migraine in the text. We also look for release date, gender of artist and musical genre.

Results:

The word migraine has been found in 52 songs. The artists who have used these words are all males, with the exception of two cases. All the musicians have less than 40 years. During the three decades the prevalent genre has changed, with increase of hip-hop, rap and trap. In all cases migraine is represented with a negative connotation, associated with frustration, despair, anger and solitude. Migraine is described as an intrusive illness, a social disease, a difficult to cure physical and emotional pain.

Conclusions:

Since the lyrics of pop songs reflect the mainstream way of thinkin of young generations, migraine has still a firmly irremovable stigma of hopeless disease. During the last three decades no signs of improvements in the social background of migraine has transpired in popular songs.

Background and Aims:

Current national regulations request a three months discontinuation following a 12 months treatment cycle with monoclonal antibodies targeting CGRP. Aim of the present study was to assess migraine outcome following erenumab discontinuation and subsequent re-treatment.

Methods:

The present study was conducted at the Headache Centre – ASST Spedali Civili Brescia. Following treatment discontinuation, all enrolled patients were assessed at three months (T¹⁵) to decide whether to start re-treatment. All patients were then assessed the following month (T¹⁶).

Results:

Twenty consecutive patients were enrolled. All patients had a diagnosis of chornic migraine and medication overuse. At T¹² , all but one patient presented a significant clinical response (responder rate 95%). At T¹⁵, patients documented significantly more migraine days (16.5±1.4 vs 6.3±0.7; p < 0.001), analgesics consumption (16.1±1.6 vs 6.1±0.8; p < 0.001) and higher MIDAS scores (62.2±11.5 vs 17.1±4.3; p = 0.006), compared to T¹², with only one patient still documenting a significant clinical response. Following re-treatment, at T¹⁶, patients documented a significant improvement in terms of migraine days (11.5±0.8 vs 16.5±1.4; p = 0.001) and analgesics consumption (7.8±0.6 vs 16.1±1.6; p < 0.001) compared to T¹⁵. However, comparing data between T¹⁶ and T¹² a significant higher migraine burden was found in terms of migraine days (11.5±0.8 vs 6.3±0.7; p < 0.001) at T¹⁶.

Conclusions:

Following treatment discontinuation, a significant clinical worsening was found, despite the high clinical response during treatment, which might be due to an early interruption of a potentially disease modifying treatment.

Background and Aims:

Various evidences implicated diencephalic-mesencephalic structures in the pathogenesis of cluster headache, in particular, the hypothalamus. We previously reported in patients with chronic cluster headache (CCH) an altered connectivity between posterior hypothalamus and structures of the midbrain monoaminergic systems, such as the ventral tegmental area (VTA), substantia nigra and subthalamic nucleus. The VTA is a pivotal center of the mesocorticolimbic dopaminergic system, a functional network involved in reward processing, avoidance, and chronic pain.

We hypothesized structural abnormalities in components of the mesocorticolimbic system in patients with CCH.

Methods:

Patients with CCH (n=28; 5 females; age 45±11.7) and age- and sex- matched healthy controls were scanned for volumetric T1-weighted image and rs-fMRI images.

We segmented cortical and subcortical areas of the mesocorticolimbic system using FreeSurfer: ventral diencephalon (comprising basal forebrain, VTA, hypothalamus), hippocampus, amygdala, nucleus accumbens, frontal pole and pars orbitalis frontal cortex.

We assessed the association between the volume of each region/structure with CCH diagnosis by univariate logistic regression. Results at p<0.05 (uncorrected) were considered significant.

Results:

Higher volumes of bilateral nucleus accumbens (p=0.008 left, p=0.033 right) and ventral diencephalon (p=0.024 left, p=0.040 right), left pars orbitalis (p=0.035), bilateral frontal pole (p=0.047 left, p=0.039 right) and right hippocampus (p=0.025) were associated with CCH.

Conclusions:

CCH patients showed increased volumes in certain structures of the mesocorticolimbic system, opposite to what commonly seen in other chronic pain conditions. Therefore, CCH seems to be characterized by a peculiar alteration in systems involved in affection and motivation.

Acknowledgements

This work was supported by the Italian Ministry of Health (RF-2016-02364909)

Background and Aims:

Although the majority of migraine with aura patients experiences pure visual aura (pvMwA), a discrete percentage also reports somatosensory, dysphasic or motor symptoms (cMwA). The wide aura clinical spectrum led to investigate whether the heterogeneity of aura phenomenon could be subtended by different neural correlates, suggesting an increased visual cortical excitability in cMwA. We aimed to explore whether cMwA patients are characterized by more pronounced connectivity changes of the visual network and whether putative abnormalities may extend beyond the visual network encompassing also the sensorimotor network in cMwA patients when compared to pvMwA patients.

Methods:

By using a RS-fMRI, we compared the RS-Fc of both visual and sensorimotor networks in 20 cMwA patients in comparison with 20 pvMwA patients and 20 migraine without aura patients.

Results:

cMwA patients showed a significantly higher RS-Fc of the left lingual gyrus, within the visual network, and of the right anterior insula, within the sensorimotor network, when compared to both pvMwA and MwoA patients (p<0.001), a difference that was able to discriminate cMwA patients from pvMwA patients as demonstrated by logistic regression analysis (AUC: 0.83).

Conclusions:

Our findings suggest that “hyper-connected” cortical areas involved in visual and somatosensory processing represent the breeding ground for CSD wave ignition and propagation. More specifically, we speculate that the higher RS-Fc of the extrastriate cortex might promote the CSD initiation representing the neural correlate of pure visual aura that can propagate to sensorimotor regions, if an increased insula RS-Fc coexists, leading to more complex aura phenotypes.