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Calling #MedTwitter history buffs: What killed Alexander the Great?
Was it a pathogen
? Too much wine
? A trusted Roman centurion 
?
The common census is that he died of malaria or maybe typhoid fever, but the real answer may be more dreadful & preposterous: A thread
Calling #MedTwitter history buffs: What killed Alexander the Great?Was it a pathogen
? Too much wine? A trusted Roman centurion ?The common census is that he died of malaria or maybe typhoid fever, but the real answer may be more dreadful & preposterous: A thread
2/
Alexander the Great (hereafter ATG) was a Macedonian king undefeated in battle. He spent most of his life in military conquest & founded numerous cities before dying at 32
A larger-than-life personality, he was of short stature, handsome, & vivacious with a "tilted head"
Alexander the Great (hereafter ATG) was a Macedonian king undefeated in battle. He spent most of his life in military conquest & founded numerous cities before dying at 32
A larger-than-life personality, he was of short stature, handsome, & vivacious with a "tilted head"
3/
Born to Philip II & tutored by Aristotle, his father had considerable influence on him, modeling triumph, tenacity (often ignoring major wounds), & competitiveness in battle
His legacy is prolific. He Hellenized the known world & is 1 of history's most influential people
Born to Philip II & tutored by Aristotle, his father had considerable influence on him, modeling triumph, tenacity (often ignoring major wounds), & competitiveness in battle
His legacy is prolific. He Hellenized the known world & is 1 of history's most influential people
4/
The circumstances surrounding his demise in Babylon in 323 BC are well-documented but controversial. Let's take a look at his enigmatic death in greater detail & through a medical lens
Out of curiosity, what did you learn killed him? Write-in below if it's not in the poll
The circumstances surrounding his demise in Babylon in 323 BC are well-documented but controversial. Let's take a look at his enigmatic death in greater detail & through a medical lens
Out of curiosity, what did you learn killed him? Write-in below if it's not in the poll
5/
Most of what we know comes from Ptolemy's Royal Journals. They're lost now but are summarized by Arrian & Plutarch (Greek writers of the Roman Empire)
They appear to be our most reliable sources, yet some say they were falsified to avoid disparaging ATG's reputation
Most of what we know comes from Ptolemy's Royal Journals. They're lost now but are summarized by Arrian & Plutarch (Greek writers of the Roman Empire)
They appear to be our most reliable sources, yet some say they were falsified to avoid disparaging ATG's reputation
6/
Regardless, toxicologists, criminal psychologists, forensic pathologists, anthropologists, & the broader medical community have lent their expertise to help elucidate the most likely cause(s)
Here's my summary of pertinent symptoms signs & context
https://www.nejm.org/doi/full/10.1056/NEJM199806113382411
Regardless, toxicologists, criminal psychologists, forensic pathologists, anthropologists, & the broader medical community have lent their expertise to help elucidate the most likely cause(s)
Here's my summary of pertinent symptoms signs & context
https://www.nejm.org/doi/full/10.1056/NEJM199806113382411
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+ Multiple d. heavy EtOH
+ Acute stabbing sensation to back s/p large cup of unmixed wine
+ F/C, sweats, tender RUQ
felt better
+ Day 4 Fever
anorexia, fatigue
+ Day 6 Lost voice
+ Day 8 Fever
symmetric paralysis, slow deep RR
+ Day 11 Coma, death
+ Day 17 No death stigmata
+ Multiple d. heavy EtOH
+ Acute stabbing sensation to back s/p large cup of unmixed wine
+ F/C, sweats, tender RUQ
felt better+ Day 4 Fever
anorexia, fatigue+ Day 6 Lost voice
+ Day 8 Fever
symmetric paralysis, slow deep RR+ Day 11 Coma, death
+ Day 17 No death stigmata
NOTE: Some details may be fabricated. His reputation was famed & many thought he was a god (incl. ATG himself). Whether his body resisted decomposition or not is completely unprovable.
Plus, in antiquity death was established by absence of RR
not HR 
( https://bit.ly/3tW5BKX )
Plus, in antiquity death was established by absence of RR
not HR ( https://bit.ly/3tW5BKX )
8/
Complicating factors:
o Inconsistent accounts of his death
o Recent battle wounds & hemothorax from arrow
o Febrile illness after bath in Cydnus river (Cilia) yrs b4
o H/o marches across Asia Minor, ME, Indiasoldiers tired, protested, mistrusted him
o Had numerous enemies
Complicating factors:
o Inconsistent accounts of his death
o Recent battle wounds & hemothorax from arrow
o Febrile illness after bath in Cydnus river (Cilia) yrs b4
o H/o marches across Asia Minor, ME, India
soldiers tired, protested, mistrusted himo Had numerous enemies
9/
Common theories:
SURGICAL: Pancreatitis, ulcer perf, Boerhaaves, carotid a dissect 2/2 cerv scoliosis, cholangitis
POISONING: C. maculatum, arsenic, Pb, strychnine, curare
INFECTIOUS: Typhoid, malaria, schistosomiasis, WNV
Fulm livr fail
Methanol
Exhausted/depressed
Porphyria
Common theories:
SURGICAL: Pancreatitis, ulcer perf, Boerhaaves, carotid a dissect 2/2 cerv scoliosis, cholangitis
POISONING: C. maculatum, arsenic, Pb, strychnine, curare
INFECTIOUS: Typhoid, malaria, schistosomiasis, WNV
Fulm livr fail
Methanol
Exhausted/depressed
Porphyria
10/
Unfortunately, no theory completely explains the course of ATG's death. In fact, hardly any of them adequately address how his body stayed mostly intact almost a week later
There has to be another etiology that includes this important, albeit bizarre, piece of the puzzle
Unfortunately, no theory completely explains the course of ATG's death. In fact, hardly any of them adequately address how his body stayed mostly intact almost a week later
There has to be another etiology that includes this important, albeit bizarre, piece of the puzzle
11/
Dr. Katherine Hall, senior lecturer at Dunedin School of Medicine & MD, suggests Guillain-Barré Syndrome (GBS)
She postulates that C. jejuni infection precipitated a GBS variant that caused an efferent axonal neuropathy
https://ancienthistorybulletin.org/purchase-articles-from-volume-30/ (2018, vol 32, 106-128)
Dr. Katherine Hall, senior lecturer at Dunedin School of Medicine & MD, suggests Guillain-Barré Syndrome (GBS)
She postulates that C. jejuni infection precipitated a GBS variant that caused an efferent axonal neuropathy
https://ancienthistorybulletin.org/purchase-articles-from-volume-30/ (2018, vol 32, 106-128)
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GBS is a post-infectious or -vax autoimmune condition that spares afferent nerves & targets peripheral nerves via molecular mimicry
autoantibodies against efferent nervespresents w/ acute symmetrical ascending paralysis
Most cases resolve, some progress to resp failure
GBS is a post-infectious or -vax autoimmune condition that spares afferent nerves & targets peripheral nerves via molecular mimicry
autoantibodies against efferent nervespresents w/ acute symmetrical ascending paralysisMost cases resolve, some progress to resp failure
13/
Does it fit?
Abd pain
Preceding febrile dz
C. jejuni endemic
Acute progressive ascend paralysis
Pseudothanatos w/ compos mentis
If correct, Dx of GBS may suggest the possibility that ATG didn't have stigmata of death bc 1) hadn't died yet or even 2) died way later
Does it fit?
Abd painPreceding febrile dzC. jejuni endemicAcute progressive ascend paralysisPseudothanatos w/ compos mentisIf correct, Dx of GBS may suggest the possibility that ATG didn't have stigmata of death bc 1) hadn't died yet or even 2) died way later
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To be fair, there is a plethora of supplementary context missing in this #Tweetorial, but I did my best to support what I thought was a reasonable argument
Are you convinced of the GBS theory? Let's repeat the poll & see what you think
For more: https://bit.ly/3jMHsBI
To be fair, there is a plethora of supplementary context missing in this #Tweetorial, but I did my best to support what I thought was a reasonable argument
Are you convinced of the GBS theory? Let's repeat the poll & see what you think
For more: https://bit.ly/3jMHsBI
15/
Thank you to my Dad, who provided an enormous amount of research for the case & for piquing my interest in the topic. Also thank you @AvrahamCooperMD for content review & advice
#MedTwitter #MedEd
Further reading:
https://amzn.to/2NI2nQm https://bit.ly/3aWOa44
Thank you to my Dad, who provided an enormous amount of research for the case & for piquing my interest in the topic. Also thank you @AvrahamCooperMD for content review & advice
#MedTwitter #MedEd Further reading:
https://amzn.to/2NI2nQm https://bit.ly/3aWOa44
