Background and Aims:

to assess the changes the central retinal artery (CRA) blood flow by the orbital color-coded Doppler sonography in patients with idiopathic intracranial hypertension (IIH) and its relation with the optic nerve (ON) elasticity assessed by shear wave elastography (SWE).

Methods:

This study was carried out on 68 eyes of patients diagnosed with IIH and 32 eyes of healthy controls. The severity of papilledema in IIH patients were sub-classified into mild and moderate/severe group. Color coded Doppler was used to measure the peak systolic velocity (PSV), end diastolic velocity (EDV), mean velocity (Vmean) and pulsatility index (PI) of the CRA.

Results:

There was significantly higher PSV, Vmean and SWE (p=0.001) of ON in patients with IIH than controls. The optimal cut-off value of PSV and Vmean of the CRA for differentiating IIH patients from controls were 11.25 and 6.75 cm/sec with AUC 0.81 and 0.785 respectively. Combined PSV, Vmean and SWE differentiating IIH patients from controls revealed AUC 0.92 and accuracy 91%. There was significant difference of PSV, Vmean and SWE between mild versus moderate/severe papilledema (p=0.001). The PSV and Vmean were correlated to the papilledema (r=0.790 and 0.722 respectively) and SWE (r=0.818 and 0.761 respectively).

Conclusions:

IIH is associated with decreased ON elasticity and reduced CRA blood flow. Individual and combined color coded Doppler of the CRA and SWE help in diagnosis of IIH. The CRA hemodynamic changes are correlated with the papilledema severity and with the extent of the biomechanical changes in the ON represented by the SWE.

Background and Aims:

To assess the long-term effectiveness, safety and tolerability of erenumab in a real-world migraine population, looking for putative predictors of responsiveness.

Methods:

In 48-week, multicenter (n=15) longitudinal cohort real life study, all consecutive adult patients with high-frequency episodic migraine (HFEM) or chronic migraine (CM) received erenumab 70 mg monthly. Change in monthly migraine days (MMD) at weeks 45-48 compared to baseline was the primary efficacy endpoint. Secondary endpoints encompassed change in monthly analgesic intake (MAI), ≥50%, ≥75%, or 100% response rates, VAS and HIT-6 scores.

Results:

Of the 242 patients treated with >1 dose, 221 received erenumab for >48 weeks. Patients had >3 prior preventive treatments failures. Most subjects received 140 mg. From baseline to weeks 45-48, erenumab reduced MMD by 4.3 days in HFEM and 12.8 in CM. VAS and HIT-6 were decreased by 1.8 and 12.3 in HFEM, and 3.0 and 13.1 in CM. MAI passed from 11 to 5 in HFEM and from 20 to 6 in CM. >50% responders were 56.1% in HFEM and 75.6% in CM, >75% were 31.6% and 44.5%, and 100% responders 8.8% and 1.2% respectively. Erenumab was safe. Responsiveness predictors were allodynia (p=0.009) in HFEM and male gender (p=0.044) and baseline migraine frequency (p=0.001) in CM. Negative predictors in CM were psychiatric comorbidities (p=0.023) and prior treatment failures (p=0.004).

Conclusions:

Long-term erenumab treatment provides sustained effectiveness, safety and tolerability in HFEM or CM patients with >3 prior preventive treatment failures.

Background and Aims:

Previous studies highlighted non-headache symptoms during the prodrome or postdrome phase of migraine. This study aimed to track the evolution of non-headache symptoms through the different phases of the migraine attack.

Methods:

We enrolled 108 migraine patients. Patients were asked to recall retrospectively whether non-headache symptoms occurred during the prodrome, headache and postdrome phase. Significant differences in the occurrence of non-headache symptoms during the three phases of migraine were assessed by Cochrane’s Q test. The co-occurrence of symptoms during the different phases was tested using Cohen’s and Fleiss’ kappa with 95% confidence intervals.

Results:

The frequency of most non-headache symptoms was different throughout the three phases, being higher during the headache than during the prodrome and postdrome phase. The symptoms with the highest co-occurrence through all three phases were food craving, neck stiffness and thirst. We found that if thirst occurs during the headache phase it is highly likely to persist during the postdrome phase; if neck stiffness occurs during the prodrome phase it will occur also during the headache phase and if yawning is present during the prodrome phase it will occur also during the postdrome phase.

Conclusions:

Although cognitive, mood and homeostatic changes are characteristics of the prodrome and postdrome phase, migraine patients most often recall having these symptoms in association to the headache pain. Thirst, food craving and neck stiffness can be mediated by the hypothalamus. These symptoms occurred throughout all three phases, suggesting a constant involvement of the hypothalamus during the migraine attack.

Background and Aims:

There is evidence suggesting that both the hypothalamus and dorsal pons could be putative drivers of migraine attacks. Here, we explored whether longitudinal resting state (RS) functional connectivity (FC) changes of the pons and hypothalamus might influence migraine patients’ disease progression.

Methods:

RS functional magnetic resonance imaging (MRI) scans were acquired from 91 headache-free episodic migraine patients and 73 controls. Twenty-three patients and 23 controls underwent a clinical and MRI follow-up evaluation after 4 years. A seed-based correlation approach was used to study RS FC changes of the pons and hypothalamus, separately. The association between the hypothalamic and pontine RS FC networks was investigated using partial correlations analyses.

Results:

After 4 years, migraine patients developed an increased FC between the bilateral hypothalamus and bilateral orbitofrontal gyrus (OFG), as well as between the left pons and left cerebellum. They also experienced decreased RS FC between the right hypothalamus and the ipsilateral lingual gyrus. At baseline, the decreased hypothalamic-lingual gyrus RS FC correlated with higher migraine attack frequency. While, at follow-up, higher hypothalamic-OFG RS FC correlated with lower migraine attack frequency and higher pontine-cerebellar RS FC correlated with an increased number of migraine attacks over the years. A significant negative association between the pontine-cerebellar RS FC and the hypothalamic-lingual RS FC was found in migraine patients.

Conclusions:

Our findings support the presence of a common functional framework comprising the hypothalamic, pontine, cerebellar and visual networks that might influence migraine disease progression, as measured by changes in migraine frequency.

Background and Aims:

We have previously shown that static and dynamic resting-state functional connectivity differed in migraineurs with and without photo-, phono-, or osmophobia. Moreover, patients with photophobia had significantly different connectivity, primarily between the cerebellar lobules and other brain regions. In our previous study, we were unable to evaluate the classification accuracy for subgroups of migraineurs, and some patients with photophobia also had phono- or osmophobia. To investigate functional connectivity specific to migraineurs with photophobia, we investigated differences in static and dynamic resting-state functional connectivity between patients with and without photophobia who do not have phonophobia or osmophobia.

Methods:

Fifteen migraineurs who had photophobia but not phonophobia and osmophobia and 15 sex- and age-matched migraineurs who did not have photophobia, phonophobia, or osmophobia underwent 3-T functional magnetic resonance imaging during the interictal phase. We compared the static and dynamic resting-state functional connectivity using region-of-interest–to–region-of-interest analysis of 91 cortical, 15 subcortical, and 26 cerebellar areas.

Results:

Static resting-state functional connectivity analysis showed that patients with photophobia had ten different significant connectivity pairs. Dynamic resting-state functional connectivity analysis showed that patients with photophobia had six different significant connectivity pairs. Migraineurs with photophobia had significantly lower connectivity between the cerebellar hemisphere and the temporal region in both the static and dynamic studies than those without photophobia.

Conclusions:

Our results showed that lower resting-state functional connectivity between the cerebellar hemisphere and the temporal region is specific to migraineurs with photophobia.

Background and Aims:

Erenumab is a monoclonal antibody against CGRP receptor approved as a prophylactic treatment of migraine. It is not yet clear if its neurophysiological effects are confined to the peripheral trigeminal system or also occur at the cortical level. This study assessed the neurophysiological effects of the drug in migrainous patients unresponsive to ≥2 prophylactic treatments.

Methods:

We prospectively enrolled 20 patients. For each patient we recorded the blink reflex (nBR), after stimulation of the right supraorbital nerve with a nociception specific concentric electrode, and the non-noxious somatosensory evoked potentials (SSEPs) after repetitive electrical stimulation of the median nerve. We measured nBR R2 area-under-the-curve (AUC) and habituation, and SSEP N20-P25 amplitude and habituation. Neurophysiological measurements were recorded before and at month-1 (T1) and month-2 (T2) before each monthly erenumab injection.

Results:

At T2, erenumab reduced the severity of headache, the mean monthly headache days and tablet intake (all p=<0.001). Compared to baseline, the nBR AUC was significantly reduced at T1. An increase in SSEP habituation, was noted at T1 and, more so, at T2 compared to the baseline (slope baseline =+0.103, T1 =-0.167, T2 =-0.229, p<0.05).

Conclusions:

The results of our study show that the clinical improvement induced by Erenumab can be attributed to neurophysiological changes occurring at both the brainstem and cortical levels.

Background and Aims:

Migraine subjects experience a derangement of the nociceptive system control as the disease progresses. The endocannabinoid system may modulate the nociceptive pathways. We evaluated the nociceptive spinal modulation together with anandamide (AEA) and palmitoylethanolamide (PEA) circulating levels in patients with episodic migraine exposed to nitroglycerin (NTG - 0.9 mg, sublingual).

Methods:

We enrolled 24 patients (MiG - 33.0±8.1 years, 22 female) and 19 healthy controls (HC - 29.5±9.3, 15 female). Nociceptive withdrawal reflex and plasma AEA and PEA levels were recorded at baseline and at 30 (T30), 60 (T-60) and 120 (T-120) minutes after NTG administration. In subjects with a positive provocation test (NTG+) during the hospital observation period (180 minutes), the evaluations were repeated at migraine onset (T-MIG) and after 1 hour (T-MIG-1h).

Results:

Sixteen MiG patients (66.7%) and 0 HCs had an NTG+ response. NTG induced spinal sensitization in both NTG+ and NTG- patients, detectable as a decrease in temporal summation threshold (p=0.001 and 0.016, respectively). AEA levels significantly increased in all subjects until T-120 (p=0.035), without differences between MiG and HC groups. PEA levels significantly increased only in MiG patients at T-120 (p=0.001).

In 13 patients with NTG+ response before 180 minutes, we detected spinal nociceptive facilitation at T-MIG and at T-MIG-1h (p=0.001), and PEA increase at T-MIG-1h (p=0.031).

We did not find any correlations between neurophysiological parameters and levels of endocannabinoid mediators.

Conclusions:

NTG facilitates spinal nociceptive modulation and is associated to increased circulating PEA levels in subjects who develop a migraine. This response likely represents a compensatory anti-inflammatory/analgesic mechanism.

Background and Aims:

Except for topiramate, oral preventive treatment for chronic migraine (CM) lacks credible evidence. We conducted TOP-PRO-study, a double-blind RCT, to know whether propranolol is as efficacious (non-inferior) and safe as topiramate for the prevention of CM.

Methods:

CM patients aged above 18 years and less than 65 years of age, not on any preventive treatment were randomly allocated to receive topiramate (100 mg/day) or propranolol (160 mg/day). The primary efficacy outcome was change in migraine days per 28 days at the end of 24 weeks from baseline. A mean difference of 1.5 days per four weeks was chosen as the cut-off delta value. Safety was also assessed.

Results:

COVID-19 pandemic and lockdown halted the recruitment before the trial reached the planned sample size of 244. Of the 175 randomized patients, 95 (topiramate 46 and propranolol 49) completed the trial. At baseline, mean (± SD) migraine days were 17.3 ± 6.7 vs 17.6 ± 6.6 days for patients in the topiramate and propranolol group respectively. The mean migraine days change was -5.29 ± 1.17 vs -7.28 ± 1.14 days (p=0.226) for topiramate and propranolol groups respectively. Propranolol was found to be non-inferior and not superior to topiramate (point estimate of -1.99 with a CI of -5.23 to 1.25 days). There was no significant difference in the incidence of adverse events between the two groups.

Conclusions:

Our study found that propranolol was non-inferior, non-superior to topiramate, and equally safe for the preventive treatment of CM. (Academic study: Clinical Trials Registry-India CTRI/2019/05/018997)