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

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

Disclosures:

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

Help, I just had a seizure in my

hand!

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Horrible Herbs

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Yo! GABA GABA

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Look-a-likes

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That wasn’t a seizure; that was

a dance move

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Category 1 questions follow

Quest

ion

The primary mechanism of the toxin found in this substance.

100Category 1

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

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Adenosine receptor antagonism

100Category 1

Quest

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

200Category 1

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Coca Plant

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

Quest

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This plant native to Southeast Asia:

Hint: commonly used to ‘stun’ fish

300Category 1

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Plant: Anamirta cocculus or Fishberries

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

Quest

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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

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Camphor

400Category 1

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

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

Quest

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

500Category 1

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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

Category 2 questions follow

Quest

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Plant and mechanism of action of its toxin:

100Category 2

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

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Tobacco/Nicotinic

100Category 2

Quest

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This bane of livestock is terribly toxic.

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Cowbane or Cicuta Virosa

200Category 2

Quest

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

300Category 2

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Lathyrus Sativa (Chickling Pea)

300Category 2

Quest

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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.”

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Colchicum autumnale/autumn crocus (Colchicine)

400Category 2

Quest

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

500Category 2

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Oenanthe fistulosa (Water Dropwort)

500Category 2

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

Category 3 questions follow

Quest

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How does cocaine cause seizures?

100Category 3

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

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Adrenergic/Sympathomimetic stimulation

100Category 3

Quest

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The antidote for ingestion of this savory shroom:

200Category 3

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Pyridoxine

-Gyromitrin metabolized to Monomethylhydrazine

200Category 3

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

Quest

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300Category 3

Before Redbull and Vodka, you could get your uppers &

downers from a drink made with this plant:

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Artemisia absinthium or Wormwood

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

Quest

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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

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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.

Quest

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The toxin and mechanism, respectively, of Anamirta cocculus

500Category 3

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Toxin: Picrotoxin

Mechanism:GABA inhibitor (non-competitive)

May also inhibit glycine receptors

500Category 3

Category 4 questions follow

Quest

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Socrates did NOT eat this:

100Category 4

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Cicuta Maculata (Water Hemlock)

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

Quest

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

200Category 4

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Gyromitra Esculenta or the False Morel

200Category 4

Quest

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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

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Dicentra cucullaria/Dutchman's breeches

Toxin: Bicuculline

300Category 4

Quest

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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

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Conium maculatum or Poison Hemlock

400Category 4

Quest

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

500Category 4

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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)

Category 5 questions follow

Quest

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

100Category 5

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Amanita Muscaria or Fly agaric

100Category 5

Quest

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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.”

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Ibotenic Acid

200Category 5

Quest

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

300Category 5

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Qat or Khat (Cathinones)

300Category 5

Quest

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

400Category 5

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Strychnos Nux Vomica or

Strynchine

400Category 5

Quest

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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

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Glutamic Acid Decarboxylase Inhibition

500Category 5