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Rachel Gottlieb-Smith, MD, MHPE

Feb 3, 2022 • 12 tweets • 7 min read • Read on X

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How does botulinum neurotoxin (BoNT) work to improve chronic migraine? 🤔

⚡️ Spoiler: it's probably not what you think!

A 🧵 about BoNT & #migraine

#MedTwitter #NeuroTwitter #tweetorial

2/
Let's start with a definition: what makes a migraine "chronic?"

◾️ Headache occurs at least 1⃣5⃣ days per month
◾️ Of which at least 8⃣ have features of migraine headache
◾️ For 3⃣ months or more

From: Int'l Classification of Headache Disorders ichd-3.org/1-migraine/1-3…

3/
And a bit of history: botulinum neurotoxin (BoNT) came to be studied for chronic migraine after anecdotes suggested that BoNT injections to treat wrinkles also helped with headaches!

4/
Two randomized controlled trials called PREEMPT (Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy) showed that a form of BoNT - onabotulinumtoxinA (onabotA) - worked for the treatment of chronic migraine in adults

pubmed.ncbi.nlm.nih.gov/20647170/
pubmed.ncbi.nlm.nih.gov/20647171/

5/
PREEMPT pooled results:

◾️ Headache days/28 days actually 🔻 for both placebo & onabotA groups
◾️ But 🔻 more for onabotA group: at week 24, -8.4 for onabotA versus -6.6 for placebo

pubmed.ncbi.nlm.nih.gov/20487038/

6/
"Standard" PREEMPT protocol:
◾️ 7 head & neck muscles
◾️ 31 injections
◾️ 155 units
◾️ Every 12 weeks

➡️ Could also use "follow-the-pain" approach & inject up to 40 more units

pubmed.ncbi.nlm.nih.gov/20958294/

7/
So back to the ❓: how does it work?

BoNT acts on peripheral nerves by ✂️ SNARE proteins, which are needed for membrane fusion ➡️ 🚫 neurotransmitter release

pubmed.ncbi.nlm.nih.gov/25882077/

8/
We mostly think about its effect at the neuromuscular junction (NMJ): 🚫 acetylcholine ➡️ paralysis

📒 For a discussion of how BoNT works at the NMJ when we *don't* want it to, check out this 🧵 on infant botulism:

https://twitter.com/RGottliebSmith/status/1487474908301041673?s=20&t=98ROJ67tn62-36_EjmdFkQ

9/
But actually: BoNT also acts on sensory neurons! And that's how it's thought to work to treat chronic migraine, a sensory disease

10/
Through its actions on sensory neurons, BoNT blocks release of glutamate, substance P & calcitonin gene-related peptide (CGRP) -- neurotransmitters all involved in pain signaling

pubmed.ncbi.nlm.nih.gov/32602955/

11/
& the injection sites per the PREEMPT protocol closely match the sensory innervation of the face, scalp, and cervical region

For a more detailed review:
pubmed.ncbi.nlm.nih.gov/32602955/

@ahsheadache

12/
So in summary, for BoNT & chronic migraine:
🔑 Mechanism thought to be sensory, not motor!

⚠️: 🚫 medical advice, & onabotA is not currently FDA approved for chronic migraine in children (used off label)

For great resources on #migraine treatment:
@ahsheadache @amfmigraine

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More from @RGottliebSmith

Rachel Gottlieb-Smith, MD, MHPE

@RGottliebSmith

Jul 8, 2022

1/🧵
Ever look at an #EEG & wonder what the 🧠 squiggles mean?

This #twEEGtorial is for you

#MedTwitter #NeuroTwitter #EEGTwitter #Tweetorial

2/
Let’s start with some background:

💡 #EEG = electroencephalogram
💡 What an EEG does: records electrical activity in the 🧠

3/
You might then 🤔: how does the 🧠 create ⚡️?

A bit of neuroscience: 🧠 cells called neurons generate ⚡️ through the flow of charged ions (sodium & potassium) across their membranes

An EEG on the scalp can't detect the ⚡️ of a single neuron, but can when neurons are in sync

Read 16 tweets

Rachel Gottlieb-Smith, MD, MHPE

@RGottliebSmith

May 21, 2022

1/
The only good thing to come of finding this on my leg last week: I learned enough to write a #tweetorial about it

A 🧵/twitter PSA about what to do if a tick comes for you – & what neuro presentations you can see w/ tick-borne illnesses

#MedTwitter #NeuroTwitter #IDTwitter

2/
After time outside in a non-wooded area, I found this on my leg. I didn’t realize what it was, so I grabbed it & flung it off... only to then find a very active, crawling tick on my counter. 😱

So after freaking out for a moment (or 2), I had to figure out what to do with it.

3/
Memories from med school flashed into my head of what you’re SUPPOSED to do:

1⃣ Remove tick w/ tweezers
2⃣ Grab close to skin & pull tick off without twisting so it doesn’t break apart
3⃣ Disinfect

Since I had already accidentally messed up 1⃣ & 2⃣, I started w/ 3⃣

Read 17 tweets

Rachel Gottlieb-Smith, MD, MHPE

@RGottliebSmith

Apr 15, 2022

1/🧵
What’s going on in the 🧠 that causes motion sickness – and what’s the link with #migraine?

A #tweetorial about motion sickness, the importance of matching, and why serotonin matters

#MedTwitter #NeuroTwitter

2/
First, let’s review some structures of the vestibular system that help us sense body movement:

1⃣ Semicircular canals = angular acceleration
2⃣ Otoliths (utricle & saccule) = linear acceleration & head tilt

📷: cell.com/current-biolog…

3/
The 🧠 combines this vestibular input with visual 👀 & proprioceptive input to assess motion

➡️ This is where the importance of matching comes in

...So what happens when the inputs don't match?

Read 10 tweets

Rachel Gottlieb-Smith, MD, MHPE

@RGottliebSmith

Feb 13, 2022

1/
#MedTwitter: ever learn a mnemonic that you can’t remember 5 minutes later? 🙋‍♀️

What makes a mnemonic useful (or not)?

A 🧵 about the good – and the bad – of mnemonics

#MedEd #NeuroTwitter #Tweetorial

2/
First, some background:

Mnemonic = relating to memory

Mnemonic devices/techniques (often called mnemonics for short) = memory aids or strategies that help with recall

Goal: transition info from working memory to long-term memory (and then be able to retrieve it later!)

3/
Let’s review 3 mnemonic techniques:

1⃣ Method of loci AKA “memory palace”
▪️ Type of imagery mnemonic
▪️ Info mentally placed at important landmarks along an imagined path ➡️ recall by re-tracing the route
▪️ Vivid images are helpful

Image from pubmed.ncbi.nlm.nih.gov/33613393/

Read 11 tweets

Rachel Gottlieb-Smith, MD, MHPE

@RGottliebSmith

Jan 22, 2022

1/
What's the best strategy for effective - and time efficient - teaching in clinic?

A 🧵 for 4⃣ teaching strategies when 🕗 is limited (& how they might be used in #neurology)

#MedEd #NeuroTwitter

pubmed.ncbi.nlm.nih.gov/18276715/
pubmed.ncbi.nlm.nih.gov/29383053/

2/
1⃣ One-minute preceptor (initially called: 5-step microskills)
pubmed.ncbi.nlm.nih.gov/1496899/

5 steps & examples 👇

Pros:
✅ Assess learner's knowledge
✅ 👍 & constructive feedback "built in"
✅ Clinical reasoning
✅ Good for novice learners

Cons:
⛔️ "1 min" is a bit unrealistic

3/
2⃣ SNAPPS
pubmed.ncbi.nlm.nih.gov/14507619/

Pros:
✅ Very learner-driven
✅ Aligns well w/ traditional presentation model
✅ Clinical reasoning

Cons:
⛔️ May not work as well for novice learners

Read 7 tweets

Rachel Gottlieb-Smith, MD, MHPE

@RGottliebSmith

Jan 13, 2022

@MedTweetorials

1/🧵
What's your favorite anti-seizure medication (ASM)?

If you said levetiracetam (LEV), you're not alone.

Why do so many #neurologists ♥️ LEV? A #tweetorial.

#MedStudentTwitter #NeuroTwitter #MedTwitter @MedTweetorials

2/
What's so good about LEV? First, some #pharmacology:

✅ Fast PO absorption
✅ 1:1 PO:IV 💉
✅ Few med interactions
✅ Can load for status epilepticus

pubmed.ncbi.nlm.nih.gov/31029217/

3/
And lots of clinical uses:

1⃣ Focal and generalized seizures
2⃣ From 👶 to 🧓
3⃣ Often used in 🤰 (category C): pubmed.ncbi.nlm.nih.gov/28472982/
4⃣ Good for status epilepticus (60 mg/kg, up to 4500 mg) - similar efficacy to phenytoin & valproic acid:
pubmed.ncbi.nlm.nih.gov/32203691/