Rationale for use of onabotulinum toxin A (BOTOX) in chronic migraine

Chronic migraine is a severely disabling headache evolving from episodic migraine as a result of different transforming factors and characterized by atypical pain modulation and peripheral and central sensitization. Discovered by serendipity, onabotulinum toxin A (BoNT-A) represents the only drug specifically approved for CM prophylaxis. According to the dominant opinion, BoNT-A acts peripherally, impairing the exocytosis of neuropeptide and neurotransmitter and the delivery of receptors and ion channels on the cell surface of peripheral trigeminal endings, thereby indirectly reducing central sensitization. However, it is not excluded that BoNT-A has also a central antinociceptive action, probably associated with an enhanced opioidergic and GABA-ergic transmission. This review discusses the rationale for use of BoNT-A in CM including its mechanisms of action and molecular targets and provides suggestions for a more tailored BoNT-A prophylaxis in patients with CM.     

Pharmacological Trials in Migraine: It's Time to Reappraise Where the Headache Is and What the Pain Is Like

Most pharmacological trials deal with migraine as if it were a clinically homogeneous disease, and when detailing its characteristics, they usually report only the presence, or absence, of aura and attack frequency but provide no information on pain location, a non‐trivial clinical detail. The past decade has witnessed growing emerging evidence suggesting that individuals with unilateral pain, especially those with associated unilateral cranial autonomic symptoms, are more responsive than others to trigeminal‐targeted symptomatic and preventive therapy with drugs such as triptans or botulinum toxin. A simple way for migraine research treatment to take a step forward might be to step back, reappraise, and critically evaluate easily obtainable patient‐reported clinical findings along with current knowledge on pain features.     

Establishment of a biorepository for migraine research: the experience of Interinstitutional Multidisciplinary BioBank (BioBIM)

The development of Biobanks and recent advances in molecular biology have enhanced the possibility to accelerate translational research studies. The Interinstitutional Multidisciplinary BioBank (BioBIM) is organized in a large healthy donors collection and pathology-based biobanks with the aim to provide a service for development of interdisciplinary studies. A new pathology-based biobank has been organized to specifically collect biospecimen from patients affected by migraine, with the final goal to centralize data, collect blood, plasma, serum, DNA and RNA of patients with this disease. The BioBIM is fully equipped for the automation of sampling/processing, storage and tracking of biospecimens. Standard Operating Procedures have been developed for processing and storage phases as well as archive of clinical data. The availability of biospecimens and clinical data will constitute a resource for various research projects.     

Trigeminal-Targeted Treatments in Migraine: Is 60% the Magic Number?

Trigeminal-targeted treatments (TTTs), the most specific and selective therapeutic migraine approach to date, are effective in approximately 60% of patients regardless of treatment type or mechanism , at least if used alone. Sixty percent is also the proportion of migraineurs who develop migraine-like episodes following experimental intravenous administration of trigeminal neuropeptides and roughly 60% is the percentage of patients with a unilateral migraine tracing the area of cutaneous distribution of the trigeminal ophthalmic branch. Hence, mechanisms other than the trigeminovascular activation are probably involved in the 40% of migraineurs who do not respond to TTTs. A closer cooperation between clinical and basic neuroscientists is needed to explore migraine models because only a careful appraisal of migraine endophenotypes may help to unravel their underlying multifaceted pathophysiological machinery.     

Pharmacotherapy for acute migraines in children and adolescents

Introduction: Migraine is increasingly recognized as an extremely burdensome and disabling disorder in both children and adolescents. A proper treatment plan is needed to improve the quality of life of both children and families as well as to minimize the risk of disease progression.

Areas covered: This review focuses on the current pharmacotherapy for acute migraine in pediatric populations, taking into account specific considerations for those drugs tested in randomized, placebo-controlled trials (RCTs).

Expert opinion: A large number of RCTs have documented the efficacy, tolerability, and safety of different compounds. Triptans appears more effective than placebo but results are variable and inconsistent. Almotriptan and rizatriptan are effective as oral formulations, as well as sumatriptan and zolmitriptan as both oral and nasal spray formulations. Adding non-steroidal anti-inflammatory drugs (NSAIDs) reinforces triptan’s effectiveness. Furthermore, small RCTs have documented both the efficacy of ibuprofen and the ineffectiveness of acetaminophen. Naproxen, ketoprofen, diclofenac, and indomethacin – NSAIDs effective in acute migraines in adults – should be tested also in pediatric subjects. Furthermore, the authors suggest that dopamine receptor antagonists should be considered in cases of severe migraines. Lastly, better designed RCTs are needed to fine-tune current therapeutic resources.     

Conversion from chronic to episodic migraine in patients treated with galcanezumab in real life in Italy: the 12-month observational,longitudinal, cohort multicenter GARLIT experience

Journal of Neurology - To investigate in real-life the conversion from chronic migraine (CM) to episodic migraine (EM), specifically to EM with High-Frequency (HFEM: 8–14 monthly migraine...     

Autosomal dominant lateral temporal epilepsy: absence of mutations in ADAM22 and Kv1 channel genes encoding LGI1-associated proteins

Mutations in the LGI1 gene are linked to autosomal dominant lateral temporal epilepsy (ADTLE) in about half of the families tested, suggesting that ADLTE is genetically heterogeneous. Recently, the Lgi1 protein has been found associated with different protein complexes and two distinct molecular mechanisms possibly underlying ADLTE have been hypothesized: the one recognizes Lgi1 as a novel subunit of the presynaptic Kv1 potassium channel implicated in the regulation of channel inactivation, the other suggests that Lgi1 acts as a ligand that selectively binds to the postsynaptic receptor ADAM22, thereby regulating the glutamate-AMPA neurotransmission. Both mechanisms imply that LGI1 mutations result in alteration of synaptic currents, though of different types. Since their protein products have been found associated with Lgi1, the Kv1 channel subunit genes KCNA1, KCNA4, and KCNAB1 and ADAM22 can be considered strong candidates for ADLTE. We sequenced their coding exons and flanking splice sites in the probands of 9 carefully ascertained ADLTE families negative for LGI1 mutations. We failed to detect any mutation segregating with the disease, but identified several previously unreported polymorphisms. An association study of four non-synonymous variants (three found in ADAM22, one in KCNA4) in a population of 104 non-familial lateral temporal epilepsy cases did not show any modification of susceptibility to this disorder. Altogether, our results suggest that neither ADAM22 nor any of the three Kv1 channel genes are major causative genes for ADLTE.     

Rizatriptan in migraineurs with unilateral cranial autonomic symptoms: a double-blind trial

The objective and background is to confirm in a double-blind, placebo-controlled study the high triptan response rates we had previously reported in an open study in migraine patients with unilateral cranial autonomic symptoms. In this randomized, double-blind, placebo-controlled study 80 migraineurs with unilateral cranial autonomic symptoms were assigned to receive rizatriptan 10 mg wafer or placebo (ratio 1:1) and treated for a single moderate or severe migraine attack. The primary endpoints were pain freedom at 2 h and total migraine freedom at 2 h. Secondary endpoints included pain relief, no associated symptoms and sustained pain freedom or relief. Significantly more patients reported pain freedom at 2 h after taking rizatriptan (54 %) than after placebo (8 %) (therapeutic gain 46 % [28 %; 64 %]; P < 0.001). Similarly, significantly more patients reported total migraine freedom at 2 h after rizatriptan (51 %) than after placebo (8 %) (therapeutic gain 43 % [26 %; 61 %]; P < 0.001). Rizatriptan was also more effective than placebo on most secondary endpoints. We confirm in a placebo-controlled study our previous data suggesting that the presence of unilateral cranial autonomic symptoms in migraineurs predicts a positive response to triptans, probably owing to intense trigeminal peripheral afferent activation which strongly recruits peripheral neurovascular 5-HT1B/1D receptors. Acute and preventive pharmacological trials in migraine should focus also on this subset of migraine patients.