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Migraine and the role of CGRP by יואל קסלר

Migraine is a disease that is extremely prevalent in the population. It is most frequently divided into 2 types; migraine with aura and migraine without aura. It can occur as episodic migraine which is defined as less than 15 migraine days per month, and chronic migraine that occurs on 15 or more days a month. Migraines can be triggered by many factors including certain types of food, alcohol, sleep deprivation, and stress. Additionally, genetic factors are thought to play a significant role in a person's risk for developing migraines.

CGRP or calcitonin gene related peptide has been well studied and found to play an important role in both the brain and peripheral nervous system in the development and evolution of a migraine. As such, it has long been thought to be an ideal target for migraine therapy.

Currently, there are a number of medications available which target the CGRP pathway. The best studied ones are the monoclonal antibodies. These antibodies target either the CGRP ligand (fremanezumab, galcanezumab, epitinezumab) or the CGRP receptor (erenumab). These are administered by subcutaneous injection or intravenously (epitinezumab) Additionally, an oral class referred to as gepants was recently approved for marketing in some countries.

All these drugs have been shown to be effective in preventing migraines. The most common side effects are local allergic reactions. Most are mild, but severe allergic reactions have been reported with all the drugs. Additionally, erenumab has been reported to cause high blood pressure and constipation which in some cases have been serious.

Additional information can be found here:

Calcitonin Gene-Related Peptide (CGRP) Antagonists: A comprehensive review of safety, efficacy and prescribing information

CGRP antagonists for decreasing migraine frequency: New options, long overdue Julia Bucklan, DO and Zubair Ahmed, MD

AIMOVIG vs. AJOVY vs. EMGALITY vs. VYEPTI. BATTLE OF THE CGRP MONOCLONAL ANTIBODY ANTAGONISTS; WHAT ARE THE DIFFERENCES AND WHICH IS BEST FOR YOU?

American Migraine Foundation

Additional articles on this topic are available here.

Music and the Brain @ יואל קסלר Blog

Music has been an essential component in human cultural development. Early musical instruments made out of bone were found by archeologists dating as early as 40,000 years ago. It has long been thought that the brain pathways that allow the learning of certain components of music such as absolute pitch can only be learned by the young developing brain. After a certain age these pathways become less "plastic" and we are less able to learn. A study by researchers in France, Canada, and the US suggest that these pathways may be able to be reopened. They found that young men who were given a drug called valproate, which is used to treat epilepsy, learned to identify pitch much better that those receiving placebo. Read the article here.

In this post at יואל קסלר .com we present a fascinating video where expert neuroscientists who study how human perceive, process, and understand music discuss the current thinking in the field. Additionally, famous musician Bobby Mc Ferrin demonstrates how we all have innate ability to appreciate and anticipate musical progressions and how this is seen from early human civilizations. It also discusses how music has evolved differently in different cultures around the world and how our ability to reproduce and anticipate musical progressions differs depending on the type of music we are used to listening to.

Additionally, the more we learn about how the brain works we understand its potential role in healing. The following from Harvard University explains:

Activating the Brain

The process by which we’re able to perceive a series of sounds as music is incredibly complex, Silbersweig and BWH psychiatry colleague Samata Sharma, MD, explained in a 2018 paper on the neurobiological effects of music on the brain. It starts with sound waves entering the ear, striking the eardrum, and causing vibrations that are converted into electric signals. These signals travel by sensory nerves to the brainstem, the brain’s message relay station for auditory information. Then they disperse to activate auditory (hearing) cortices and many other parts of the brain. It is noteworthy that different parts of the brain are activated, depending on the type of music—for example, melodic versus dissonant—and whether we are listening, playing, learning, or composing music (see related box).

Music can alter brain structure and function, both after immediate and repeated exposure, according to Silbersweig. For example, musical training over time has been shown to increase the connectivity of certain brain regions. “If you play an instrument like the violin,” he said in a recent Zoom interview, “the areas in your brain that are associated with the frequencies of the violin are more stimulated and the synaptic connections are richer.”

Healing Power of Music

These changes in brain circuitry and connectivity suggest opportunities to activate certain regions to promote healing, Silbersweig says. He and Haddad look forward to using cutting-edge brain research to build on what’s already known about the therapeutic power of music for patients with dementia, depression, and other neurological conditions. The pair note, for instance, that playing a march or other rhythmic piece for people with Parkinson’s disease stimulates the brain circuits that get them physically moving. Similarly, people with short-term memory loss from Alzheimer’s disease often recognize familiar songs like “Happy Birthday” because “that memory’s encoded into their brain’s long-term memory,” Haddad notes.

Haddad witnessed this response during high school and college while performing for patients in hospitals and assisted living facilities. “You have these patients who are essentially sedated, lying down, eyes closed, not able to communicate,” she recalls. “And when you play a song that they recognize from their youth, their eyes light up. They’re sitting up, and they’re smiling. It’s just incredible.”

See more here.

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