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Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda, CA Yo! GABA GABA and Other Key Players in "Natural" Seizures
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Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Dec 14, 2015

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Page 1: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA

Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda, CA

Yo! GABA GABA and Other Key Players in "Natural" Seizures

Page 2: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Objectives:

Appreciate the variety of mechanisms of natural toxin-induced seizures and how they interact

Be able to visually identify at least 5 natural toxins causing seizures

Be able to describe the mechanism of seizures in at least 5 natural toxins

Page 3: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Disclosures:

Dr. Wolk is a Co-investigator for Analatro (Black Widow Fab2 Antivenom)-Instituto Bioclon/Rare Disease Therapeutics

Page 4: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Help, I just had a seizure in my

hand!

100

200

300

400

500

Horrible Herbs

100

200

300

400

500

Yo! GABA GABA

100

200

300

400

500

Look-a-likes

100

200

300

400

500

That wasn’t a seizure; that was

a dance move

100

200

300

400

500

Page 5: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Category 1 questions follow

Page 6: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Quest

ion

The primary mechanism of the toxin found in this substance.

100Category 1

http://www.flickr.com/photos/bonjourwill/4528624762/sizes/o/

http://www.flickr.com/photos/bonjourwill/4528624762/sizes/o/
Page 7: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Answ

er

Adenosine receptor antagonism

100Category 1

Page 8: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Quest

ion

Rick James may have used a certain substance derived from this plant:

200Category 1

Page 9: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Answ

er

Coca Plant

200Category 1Coca Picture Refernce: http://upload.wikimedia.org/wikipedia/commons/7/72/Colcoca04.jpg

Page 10: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Quest

ion

This plant native to Southeast Asia:

Hint: commonly used to ‘stun’ fish

300Category 1

Page 11: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Answ

er

Plant: Anamirta cocculus or Fishberries

300Category 1Picture Reference: http://upload.wikimedia.org/wikipedia/commons/7/70/Anamirta_cocculus_02.JPG

Page 12: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Quest

ion

This toxin is derived from a large tree with broad-leaves.

It is native to China and Japan, but is considered an invasive species in the Southern United States.

400Category 1

Page 13: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Answ

er

Camphor

400Category 1

http://plants.ifas.ufl.edu/misc/reco_cards/cincam.pdf

http://i00.i.aliimg.com/photo/v0/105180782/Camphor_Bulk.jpg

http://plants.ifas.ufl.edu/misc/reco_cards/cincam.pdf
http://i00.i.aliimg.com/photo/v0/105180782/Camphor_Bulk.jpg
Page 14: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Quest

ion

Latin name for the genus, toxin and mechanism of toxicity:

500Category 1

Page 15: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Answ

er

Aconitum, Aconitine, & Sodium-Channel Blockade

Also known as Wolfsbane or Monskhood

500Category 1

Picture Reference: http://upload.wikimedia.org/wikipedia/commons/7/70/Aconitum_napellus_Ticino.jpg

http://upload.wikimedia.org/wikipedia/commons/7/70/Aconitum_napellus_Ticino.jpg
Page 16: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Category 2 questions follow

Page 17: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Quest

ion

Plant and mechanism of action of its toxin:

100Category 2

http://farm9.staticflickr.com/8301/7808736868_5ce5abf011_b.jpg Creative Commons License

http://farm9.staticflickr.com/8301/7808736868_5ce5abf011_b.jpg
http://farm9.staticflickr.com/8301/7808736868_5ce5abf011_b.jpg
Page 18: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Answ

er

Tobacco/Nicotinic

100Category 2

Page 19: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Quest

ion

This bane of livestock is terribly toxic.

200

Page 20: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Answ

er

Cowbane or Cicuta Virosa

200Category 2

Page 21: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Quest

ion

This edible ‘pea’ contains the neurotoxin ẞ-N-oxalylamino-L-alanine (BOAA) which is a glutamate agonist

300Category 2

Page 22: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Answ

er

Lathyrus Sativa (Chickling Pea)

300Category 2

Page 23: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Quest

ion

This fall flower may give you seizures, but that could be the least of your problems:

400Category 2

http://s0.geograph.org.uk/photos/54/59/545962_fd7cb876.jpg“© Copyright Evelyn Simak and licensed for reuse under this Creative Commons Licence.”

http://s0.geograph.org.uk/photos/54/59/545962_fd7cb876.jpg
Page 24: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Answ

er

Colchicum autumnale/autumn crocus (Colchicine)

400Category 2

Page 25: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Quest

ion

This relative of water hemlock from the island of Sardinia may give you a Sardonic Grin:

500Category 2

Page 26: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Answ

er

Oenanthe fistulosa (Water Dropwort)

500Category 2

http://commons.wikimedia.org/wiki/File:Illustration_Oenanthe_aquatica0.jpg

http://commons.wikimedia.org/wiki/File:Illustration_Oenanthe_aquatica0.jpg
http://commons.wikimedia.org/wiki/File:Illustration_Oenanthe_aquatica0.jpg
Page 27: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Category 3 questions follow

Page 28: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Quest

ion

How does cocaine cause seizures?

100Category 3

http://farm3.staticflickr.com/2190/2170100460_2094dd2d6d_o.jpg

http://farm3.staticflickr.com/2190/2170100460_2094dd2d6d_o.jpg
http://farm3.staticflickr.com/2190/2170100460_2094dd2d6d_o.jpg
Page 29: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Answ

er

Adrenergic/Sympathomimetic stimulation

100Category 3

Page 30: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Quest

ion

The antidote for ingestion of this savory shroom:

200Category 3

Page 31: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Answ

er

Pyridoxine

-Gyromitrin metabolized to Monomethylhydrazine

200Category 3

Picture Reference: http://upload.wikimedia.org/wikipedia/commons/9/97/Fr%C3%BChjahrslorchel.JPG

http://upload.wikimedia.org/wikipedia/commons/9/97/Fr%C3%BChjahrslorchel.JPG
Page 32: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Quest

ion

300Category 3

Before Redbull and Vodka, you could get your uppers &

downers from a drink made with this plant:

Page 33: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Answ

er

Artemisia absinthium or Wormwood

300Category 3Picture Reference: http://upload.wikimedia.org/wikipedia/commons/f/f5/Artemisia_absinthium_0002.JPG

Page 34: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Quest

ion

400Category 3

Mechanism of this toxin found in mussels; linked to severe permanent neurologic damage and the deaths of > 400 Sea Lions:

http://cleanfish.com/system/images/BAhbB1sHOgZmIjsyMDExLzAzLzIxLzE2LzUwLzMyLzMxMS9TYWx0U3ByaW5nX011c3NlbHNfV2hvbGVfOC5qcGdbCDoGcDoKdGh1bWIiDTQ1MHg0NTA+/SaltSpring_Mussels_Whole_8.jpg

http://cleanfish.com/system/images/BAhbB1sHOgZmIjsyMDExLzAzLzIxLzE2LzUwLzMyLzMxMS9TYWx0U3ByaW5nX011c3NlbHNfV2hvbGVfOC5qcGdbCDoGcDoKdGh1bWIiDTQ1MHg0NTA+/SaltSpring_Mussels_Whole_8.jpg
http://cleanfish.com/system/images/BAhbB1sHOgZmIjsyMDExLzAzLzIxLzE2LzUwLzMyLzMxMS9TYWx0U3ByaW5nX011c3NlbHNfV2hvbGVfOC5qcGdbCDoGcDoKdGh1bWIiDTQ1MHg0NTA+/SaltSpring_Mussels_Whole_8.jpg
http://cleanfish.com/system/images/BAhbB1sHOgZmIjsyMDExLzAzLzIxLzE2LzUwLzMyLzMxMS9TYWx0U3ByaW5nX011c3NlbHNfV2hvbGVfOC5qcGdbCDoGcDoKdGh1bWIiDTQ1MHg0NTA+/SaltSpring_Mussels_Whole_8.jpg
http://cleanfish.com/system/images/BAhbB1sHOgZmIjsyMDExLzAzLzIxLzE2LzUwLzMyLzMxMS9TYWx0U3ByaW5nX011c3NlbHNfV2hvbGVfOC5qcGdbCDoGcDoKdGh1bWIiDTQ1MHg0NTA+/SaltSpring_Mussels_Whole_8.jpg
Page 35: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Answ

er

Glutamate Analogue/NMDA Agonist

400Category 3Picture Reference: Figure 1 in Teitelbaum JS, Zatorre RJ, Carpenter S, Gendron D, Evans AC, Gjedde A, et al. Neurologic sequelae of domoic acid intoxication due to the ingestion of contaminated mussels. The New England journal of medicine. 1990;322(25):1781-7.

Page 36: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Quest

ion

The toxin and mechanism, respectively, of Anamirta cocculus

500Category 3

Page 37: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Answ

er

Toxin: Picrotoxin

Mechanism:GABA inhibitor (non-competitive)

May also inhibit glycine receptors

500Category 3

Page 38: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Category 4 questions follow

Page 39: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Quest

ion

Socrates did NOT eat this:

100Category 4

Page 40: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Answ

er

Cicuta Maculata (Water Hemlock)

100Category 4Picture Reference: http://www.illinoiswildflowers.info/wetland/photos/wt_hemlock1.jpg

http://www.illinoiswildflowers.info/wetland/photos/wt_hemlock1.jpg
Page 41: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Quest

ion

This “false” fungus may be “tasty” but ingestion is inadvisable

200Category 4

Page 42: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Answ

er

Gyromitra Esculenta or the False Morel

200Category 4

Page 43: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Quest

ion

The flowers of this plant may resemble the pants of a person from a Northern European country; this plant may also cause seizures in livestock:

300Category 4

http://farm5.staticflickr.com/4015/4525160667_8fb31c049c_b.jpg Creative Commons License

http://farm5.staticflickr.com/4015/4525160667_8fb31c049c_b.jpg
http://farm5.staticflickr.com/4015/4525160667_8fb31c049c_b.jpg
Page 44: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Answ

er

Dicentra cucullaria/Dutchman's breeches

Toxin: Bicuculline

300Category 4

Page 45: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Quest

ion

This bad actor causes seizures less frequently than its cousin, and may be identifiable by its coloration:

400Category 4

http://farm1.staticflickr.com/208/508080682_a19188ceb5_o.jpg Creative Commons License

http://farm1.staticflickr.com/208/508080682_a19188ceb5_o.jpg
http://farm1.staticflickr.com/208/508080682_a19188ceb5_o.jpg
Page 46: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Answ

er

Conium maculatum or Poison Hemlock

400Category 4

Page 47: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Quest

ion

This stellate assassin is sometimes mistaken for its benign Chinese cousin:

500Category 4

Page 48: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Answ

er

Illicium anisatum/Japanese star anise (Anisatin)

-non-competitive GABA (channel) inhibition

500Category 4Picture Reference: http://2.bp.blogspot.com/_a5abCT2isic/TBl3SSBhWQI/AAAAAAAACwM/P63cuGW_gzc/s400/star_anise.jpg

http://upload.wikimedia.org/wikipedia/commons/6/62/Illicium_verum_2006-10-17.jpg

For comparison: Illicium verum or

Chinese Star Anise (Non-toxic)

Page 49: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Category 5 questions follow

Page 50: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Quest

ion

The NMDA agonist in this fungus theoretically could causes seizures, but rarely does due to it’s concomitant CNS depressant

100Category 5

Page 51: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Answ

er

Amanita Muscaria or Fly agaric

100Category 5

Page 52: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Quest

ion

200Category 5

The name of the NMDA agonist in this mushroom:

http://s0.geograph.org.uk/geophotos/02/12/31/2123114_83948608.jpg

“© Copyright JamesB and licensed for reuse under this Creative Commons Licence.”

http://s0.geograph.org.uk/geophotos/02/12/31/2123114_83948608.jpg
Page 53: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Answ

er

Ibotenic Acid

200Category 5

Page 54: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Quest

ion

Chew on this, and you might get a little rush:

300Category 5

Page 55: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Answ

er

Qat or Khat (Cathinones)

300Category 5

Page 56: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Quest

ion

Found in some traditional remedies, this toxin may give you a convulsion to remember

400Category 5

Page 57: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Answ

er

Strychnos Nux Vomica or

Strynchine

400Category 5

Page 58: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Quest

ion

Specific mechanism by which this cellular asphyxiant may cause seizures (other than general cellular asphyxia):

500Category 5

http://upload.wikimedia.org/wikipedia/commons/9/9e/Autumn_Red_peaches.jpg

http://upload.wikimedia.org/wikipedia/commons/9/9e/Autumn_Red_peaches.jpg
Page 59: Christina H. Hernon, MD, University of Massachusetts Memorial Hospital, Worcester, MA Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda,

Answ

er

Glutamic Acid Decarboxylase Inhibition

500Category 5


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