Are anti-calcitonin gene-related peptide monoclonal antibodies effective in treating migraine aura? A pilot prospective observational cohort study.

BACKGROUND: About 15% to one third of migraineurs experience aura symptoms. Aura is a reversible focal neurological phenomenon involving visual, sensory, speech, and motor symptoms that usually precede migraine pain. Monoclonal antibodies against calcitonin-related peptide (anti- CGRP mAbs) are effective in preventing chronic and episodic migraine, but little is known about their effectiveness on specifically preventing migraine with aura. METHODS: This is a pilot prospective observational cohort study, aiming at evaluating the effectiveness and safety of Erenumab, Fremanezumab or Galcanezumab for the treatment of migraine aura. We enrolled 14 patients at the Headache Centre of University Federico II of Naples. Duration of follow-up was 12 months. We assessed mean monthly days with aura symptoms, with or without subsequent headache, as well as mean monthly days with headache and mean monthly MIDAS score, by reviewing standardized paper patient headache diaries every three months. RESULTS: A significant decrease in mean monthly aura days was observed throughout the observation period (median baseline: 13, interquartile range: 4-16; after 12 months: 1, interquartile range: 0-3, p < 0.001). We observed a statistically significant decrease in mean monthly headache days as well (median baseline 21, interquartile range: 16-30; after 12 months: 5, interquartile range: 4-7, p < 0.001). During the 12-month treatment period, none of the 14 patients reported mild or serious adverse events. CONCLUSION: Our findings suggest that anti-CGRP mAbs are highly effective in migraine with aura, both in reducing mean monthly aura days and mean monthly days with headache.

Recurrent reflex syncope in idiopathic intracranial hypertension patient resolved after lumbar puncture: pathogenetic implications.

BACKGROUND: Idiopathic intracranial hypertension is a disease characterized by increased intracranial cerebrospinal fluid volume and pressure without evidence of other intracranial pathology. Dural sinuses are rigid structures representing a privileged low-pressure intracranial compartment. Rigidity of dural sinus ensures that the large physiologic fluctuations of cerebrospinal fluid pressure associated with postural changes or to Valsalva effect cannot be transmitted to the sinus. An abnormal dural sinus collapsibility, especially when associated with various anatomical sinus narrowing, has been proposed as a key factor in the pathogenesis of idiopathic intracranial hypertension. This pathogenetic model is based on an excessive collapsibility of the dural sinuses that leads to the triggering of a self-limiting venous collapse positive feedback-loop between the cerebrospinal fluid pressure, that compresses the sinus, and the increased dural sinus pressure upstream, that reduces the cerebrospinal fluid reabsorption rate, increasing cerebrospinal fluid volume and pressure at the expense of intracranial compliance and promoting further sinus compression. Intracranial compliance is the ability of the craniospinal space to accept small volumetric increases of one of its compartments without appreciable intracranial pressure rise. In idiopathic intracranial hypertension, a condition associated with a reduced rate of CSF reabsorption leading to its volumetric expansion, a pathologically reduced IC precedes and accompanies the rise of ICP. Syncope is defined as a transient loss of consciousness due to a transient cerebral hypoperfusion characterized by rapid onset, short duration, and spontaneous complete recovery. A transient global cerebral hypoperfusion represents the final mechanism of syncope determined by cardiac output and/or total peripheral resistance decrease. There are many causes determining low cardiac output including reflex bradycardia, arrhythmias, cardiac structural disease, inadequate venous return, and chronotropic and inotropic incompetence. Typically, syncopal transient loss of consciousness is mainly referred to an extracranial mechanism triggering a decrease in cardiac output and/or total peripheral resistance. Conversely, the association of syncope with a deranged control of intracranial compliance related to cerebral venous outflow disorders has been only anecdotally reported. CASE PRESENTATION: We report on a 57-year-old woman with daily recurrent orthostatic hypotension syncope and idiopathic intracranial hypertension-related headaches, which resolved after lumbar puncture with cerebrospinal fluid subtraction. CONCLUSIONS: A novel mechanism underlying the triggering of orthostatic syncope in the presence of intracranial hypertension-dependent reduced intracranial compliance is discussed.

A head-to-head observational cohort study on the efficacy and safety of monoclonal antibodies against calcitonin gene-related peptide for chronic and episodic migraine.

OBJECTIVE: To compare the effectiveness and safety of galcanezumab, fremanezumab, and erenumab for the treatment of chronic and episodic migraine, through real-world data. BACKGROUND: Monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway have been tested extensively in several clinical trials for both episodic and chronic migraine, showing high effectiveness, safety, and tolerability; however, there are no prospective real-world studies intending to compare their efficacy and safety. METHODS: This is a prospective observational cohort study comparing the effectiveness and safety profiles of galcanezumab, fremanezumab, and erenumab for the treatment of chronic and episodic migraine. We enrolled 140 patients at the Headache Centre of University Federico II of Naples, with a history of multiple failed treatments with validated migraine preventatives. Framenezumab, erenumab, or galcanezumab were administered for 12 months. The mean monthly days with headache, Migraine Disability Assessment (MIDAS) score, and adverse events were evaluated during the run-in period and every 3 months by reviewing standardized paper patient headache diaries. RESULTS: We found a mean reduction of migraine monthly days from baseline of -12.0 (-9.8, -14.1) in the galcanezumab group, -12.3 (-10.2, -14.3) in the fremanezumab group, and -10.8 (-8.5, -13.1) in the erenumab group (for all, p < 0.001). We found a mean reduction of MIDAS score of -32.6 (-26.6, -38.5) in the galcanezumab group, -33.4 (-28.0, -38.9) in the fremanezumab group, and -29.2 (-23.0, -35.4) in the erenumab group (for all, p < 0.001). We found no significant differences between mAbs in the reduction of mean monthly days with headache and MIDAS score. We found a more rapid effect of galcanezumab and erenumab compared to fremanezumab in medication overuse headache patients after 3 months of treatment (-10.8 and -11.1 vs. -4.0 days; p = 0.029). CONCLUSION: Our results confirm the therapeutic benefits of anti-CGRP mAbs. There is no evidence that suggests that one antibody may be superior to the others in terms of effectiveness, both in chronic and episodic patients.

Multiple cranial neuropathy due to varicella zoster virus reactivation without vesicular rash: a challenging diagnosis.

Ramsay Hunt syndrome is due to reactivation of varicella zoster virus (VZV) dormant in the geniculate ganglion of the facial nerve. The diagnosis is typically based on clinical triad of ipsilateral facial paralysis, otalgia, and vesicles in the auditory canal or the auricle. However, Ramsay Hunt syndrome may occur without skin eruption in up to one third of patients. Moreover, the involvement of other cranial nerves in addition to the facial nerve has been also reported. Herein, we reported a case report of a man who developed a multiple cranial neuropathy caused by VZV reactivation without skin vesicular eruption. The present case underlines a possible diagnostic challenge that clinicians may hit when facing a common disorder such as peripheral facial palsy. Indeed, clinicians must be aware that Ramsay Hunt syndrome may develop without skin vesicular eruption as well it may be complicated by multiple cranial nerve involvement. Antiviral therapy is effective in VZV reactivation for recovery of nerve function.

Anti-calcitonin gene-related peptide monoclonal antibodies for the treatment of vestibular migraine: A prospective observational cohort study.

BACKGROUND: Vestibular migraine is considered the most common cause of recurrent vertigo for which specific treatments are missing. Monoclonal antibodies against calcitonin gene-related peptide,, are effective in preventing migraine. Since CGRP is also detected in human cochlear and vestibular organs it may also play a role in vestibular physiology. METHODS: This is a prospective observational cohort study, aiming at evaluating the efficacy of erenumab, fremanezumab or galcanezumab for the treatment of fifty vestibular migraine patients. We assessed mean monthly days with headache and dizziness/vestibular symptoms, pain intensity and migraine-related clinical burden occurring for 18 months. RESULTS: Response to treatment was excellent as 45 (90%) patients had at least a 50% reduction in vertigo frequency, 43 (86%) had at least a 50% reduction in headache frequency, and 40 (80%) a MIDAS reduction of at least 50%. Overall, 39 (78%) patients had a concomitant reduction of all three parameters. Mean monthly days with dizziness/vestibular symptoms showed an overall significant decrease from a mean of 10.3 ± 1.9 at baseline to 0.8 ± 0.3 days, difference 9.5 (CI 95% 3.6, 15.4; p < 0.001) after twelve months. CONCLUSION: We show that anti-CGRP mAbs may be effective in the treatment of Vestibular Migraine. Their use should be encouraged early in the disease course to allow for a better symptom control and quality of life improvement.

The putative role of trigemino-vascular system in brain perfusion homeostasis and the significance of the migraine attack.

Besides representing the place where a migraine attack generates, what is the physiological role of peptidergic control of arteriolar caliber within the trigemino-vascular system? Considering that the shared goal of most human CGRP-based neurosensory systems is the protection from an acute threat, especially if hypoxic, what is the end meaning of a migraine attack? In this paper, we have reviewed available evidence on the possible role of the trigemino-vascular system in maintaining cerebral perfusion pressure homeostasis, despite the large physiological fluctuations in intracranial pressure occurring in daily life activities. In this perspective, the migraine attack is presented as the response to a cerebral hypoxic threat consequent to a deranged intracranial pressure control aimed at generating a temporary withdrawal from the environment with limitation of physical activity, a condition required to promote the restoration of cerebral fluids dynamic balance.