Did Agrippina poison the Roman Emperor Claudius? Was General George Armstrong Custer mentally sound when he ordered the 7th Cavalry to attack at the Little Big Horn River? History is full of medical mysteries. After all, everyone has to die of something. But modern medical practitioners have actually found clues to the progress of diseases that still afflict mankind today by studying ancient sources who recorded the afflictions and demise of peoples of the past.

Saturday, February 27, 2016

Henry VIII: Did history lose a true prince of the Renaissance to traumatic brain injury?

An armored Henry VIII and his charger at the Tower of London
in London, England.  Photo by Mary Harrsch © 2006
A history resource article by  © 2015

Today, I read an interesting paper by Muhammad Qaiser Ikram, Fazle Hakim Sajjad, Arash Salardini published in the Journal of Clinical Neuroscience proposing that Henry VIII's erratic behavior, particularly after 1536, was the result of repeated traumatic brain injuries.  Furthermore, the researchers propose that his dramatic weight gain and even his leg ulcers could have been the result of post-traumatic growth hormone deficiency, one of the many afflictions that accompany traumatic brain injury.

They begin their examination of the historical record by pointing to a report by the Spanish ambassador in 1507 pronouncing “There is no finer youth in the world than the Prince of Wales”. A 16-year-old Henry was "lighthearted, merry, and easily given to laughter.” One could say this was long before Henry had experienced the heavy weight of kingship.  But eight years later in 1515, despite suffering a bout of smallpox the previous year, Henry meets with the Venetian ambassador who says of Henry he was “prudent and wise and free from every vice.”

With Henry's love of often dangerous medieval sports, especially jousting, however, his easy-going personality would not last.

"In March 1524 the king was unseated after a jousting lance found its way into his open visor and broke into many splintered pieces. Henry was de-horsed and dazed, although he continued to joust for the rest of the day. He is said to have had recurrent headaches after this point." - Muhammad Qaiser Ikram, et al, The head that wears the crown: Henry VIII and traumatic brain injury

Henry VIII's blackened, etched and gilt Italian field armor
at the Metropolitan Museum of Art in New York.
Photo by Mary Harrsch © 2007
Then, in 1525, while hawking, Henry, attempting to vault over a hedge with a pole, plunged head first into a water-filled ditch.

"He may have been dazed or unconscious because it is said of the incidence that if Edmund Mody had not pulled him out of the ditch, legs first, he may have drowned." - Muhammad Qaiser Ikram, et al, The head that wears the crown: Henry VIII and traumatic brain injury

An avid outdoorsman, Henry VIII enjoyed hunting.  Here he hunts deer with Anne Boleyn in this 1903
painting by William Powell Frith.  Image courtesy of Wikimedia Commons.
Although now plagued with headaches and having suffered two bouts of malaria, Henry still seemed amiable to court visitors.  Desiderius Erasmus, a noted Dutch Renaissance humanist, while visiting the Tudor court in 1529, described Henry as "… a man of gentle friendliness, and gentle in debate; he acts more like a companion than a king".

Then on January 24, 1536, the king was unseated while charging at full speed in a joust and his steed fell upon him.  Henry was said to be unable to speak for two hours which the researchers attribute to a loss of consciousness.

Members of Henry's court began to notice the king appeared to be suffering from significant memory problems. In July 1536, Henry's illegitimate son Henry FitzRoy, Duke of Richmond, died of tuberculosis.

"He was buried in near-secret in the presence of his father-in-law the Duke of Norfolk, and two other personages, by the king’s own instructions. Yet in a few days Henry appears to have forgotten his own role in the funeral and was accusing the Duke of Norfolk of inappropriate behavior towards FitzRoy." - Muhammad Qaiser Ikram, et al, The head that wears the crown: Henry VIII and traumatic brain injury

The researchers explain, "Traumatic brain injury disproportionately damages white matter tracts  [the cells in the brain that transmit signals from one region to another] which may manifest as amnesia, apathy and loss of initiative, executive dysfunction [executive processes include goal formation, planning, goal-directed action, self-monitoring, attention and response inhibition] as well as impulse and emotional dysregulation [radical mood swings including angry outbursts, behavior outbursts such as throwing objects or destroying things and aggression]."

In fact, his possible loss of impulse control may have led to his beheading of Queen Anne Boleyn in May 1536 and his, increasingly brutal, dissolution of the monasteries from 1535-1540. (My observation not theirs) He also married three more times during this period although the death of Jane Seymour from childbirth complications could not be attributed to Henry's mental illness.

Anne Boleyn in the Tower by Edouard Cibot, 1835.

The researchers point out that Henry began to demonstrate explosive and murderous anger that was relatively easily provoked.

"The irascibility and changeability of Henry was a source of constant anxiety for Tudor courtiers. Several ambassadors noted the unpredictability of Henry, who was often furious for reasons not immediately obvious to his ministers and advisers. The French ambassador for example speaks of his 'lightness and inconstancy' in 1540. His explosive anger could often end in the execution of an unsuspecting courtier or friend. The king was unable to control other impulses, whether these were related to his unreasonable suspicions or his lust for other peoples’ property."  - Muhammad Qaiser Ikram, et al, The head that wears the crown: Henry VIII and traumatic brain injury

Henry also suffered from depression and extended periods of self-pity.  After executing Thomas Cromwell in July 1540, Henry fell into a deep depression and in 1541, claiming to mourn Cromwell, confined himself to Hampton Court for a long period.

One of the ornate towers and Tudor-era chimneys at
Hampton Court Palace, East Molesey, England.
Photo by Mary Harrsch © 2008
Another result of traumatic brain injury that is often overlooked is damage to the pituitary gland. Such damage may result in growth hormone deficiency and hypogonadotrophic hypogonadism.  In an adult, growth hormone deficiency may result in loss of strength, stamina, and musculature, poor bone density, diminished lean body mass and visceral obesity. So Henry's ballooning weight may not have been entirely attributable to a gargantuan appetite.

Closeup of a portly Henry VIII by American miniaturist
George S. Stuart at the Museum of Ventura County, CA.
Photo by Mary Harrsch © 2006
Psychological symptoms include poor memory, social withdrawal, and depression which also coincide with reports we have already examined.

Symptoms of hypogonadism in an adult include low libido, and infertility.  You may think with court tales of countless sexual liasons and the king married six times, Henry surely must not have suffered from a diminished libido.  But, in fact, the researchers find repeated references to Henry's inability to perform in the bedroom.

"Anne and George Boleyn were accused of ridiculing the king. Anne appears to have told her sister-in-law that Henry 'was not adept in the matter of coupling with a woman and that he had neither vertu [skill] nor puissance [vigour]'." - Muhammad Qaiser Ikram, et al, The head that wears the crown: Henry VIII and traumatic brain injury

They also point to his inability to consummate his marriage to Anne of Cleves in 1540.

"Various excuses were made from 'misliking of her body for the hanging of her breast and the looseness of her flesh', to the charge that the king was duped by an unnecessarily complimentary portrait of Anne." - Muhammad Qaiser Ikram, et al, The head that wears the crown: Henry VIII and traumatic brain injury

Anne of Cleves by Bartholomäus Bruyn the Elder 1540s

The researchers also suspect Henry's disastrous marriage to Catherine Howard, a young woman who took many lovers while Henry's lack of extra-marital activity was attributed to his fidelity.  They say this seems highly unlikely in view of his long history of youthful virility and sexual indiscretions.

I find it particularly tragic that Henry's own traumatic brain injury may have been ultimately responsible for the lack of an heir he so desperately craved all of those years.

By the late 1540s, Henry's symptoms had reached catastrophic proportions affecting both his personal life and ability to lead his country.

In 1544, Henry declared war on France and besieged the town of Boulogne.  At one point he simultaneously ordered fortification of the city while issuing an oral order to demolish it.

His sixth and final wife, Catherine Parr, was not spared from his irrational tirades either.

"...the king loved religious debates and during one acrimonious argument between Catherine Parr and Gardiner [in 1546] he unreasonably ordered the transportation of the queen to the Tower of London. The next day he appears to have forgotten about the incident and was consoling his distraught wife. When the soldiers arrived to take her away, he could not remember the original orders he had given and had to be prompted to remember the episode. When he remembered he flew into another fit of rage." - Muhammad Qaiser Ikram, et al, The head that wears the crown: Henry VIII and traumatic brain injury

A miniature portrait of Catherine Parr circa 1543
by Lucas Horenbout
Within months, Henry VIII was dead.

Since his death there has been a flurry of diagnoses proposed to account for Henry's physical symptoms and erratic behavior.

 "One of the hypotheses regarding the health of Henry VIII is that he had Cushing’s syndrome [a condition with symptoms that include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, a round red face, a fat lump between the shoulders, weak muscles, weak bones, acne, and fragile skin that heals poorly]. There appears to be a temporal relationship between Henry’s documented head injuries and the stepwise worsening of his health which this hypothesis cannot explain. Another older hypothesis is that Henry had syphilis but this is now largely abandoned. Other hypothesized mechanisms for Henry’s change include diabetes and hypothyroidism, neither of which can account for the whole picture. Another recent hypothesis regarding Henry’s health is that he had McLeod syndrome [a genetic mutation with symptoms of peripheral neuropathy, cardiomyopathy and hemolytic anemia along with late-onset dementia and behavioral changes usually not noticed until the individual is in their 50s] with infertility and psychosis. Henry, however, is not reported to have had choreiform movements [irregular muscular movements that make walking difficult] or dystonic reactions [twisting and repetitive movements caused by sustained muscle contractions]." - Muhammad Qaiser Ikram, et al, The head that wears the crown: Henry VIII and traumatic brain injury

So, the researchers conclude, "We know of at least three major head injuries in Henry’s life. He may have had headaches and more subtle changes to his personality after his first head injury, but there is a marked stepwise change in him after 1536. It is entirely plausible, though perhaps not provable, that repeated traumatic brain injury lead to changes in Henry’s personality. This is not to discount the complex time in which he lived or the impact of events on him. Whether some of the metabolic problems he faced later in life can be explained in terms of his head injury is a longer bow to draw but not outside the realms of possibility."

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Tuesday, April 21, 2015

Did the Julio-Claudians suffer from congenital heart defects?

A history resource article by  © 2015

Nude statue of Julius Caesar.  Photographed at The Musée du Louvre
in Paris, France by
Mary Harrsch  
© 2008
Note: This is a cross post from one of my other history blogs, Roman Times.

A recently published article, "Has the diagnosis of a stroke been overlooked in the symptoms of Julius Caesar", by Francesco M. Galassi and Hutan Ashrafian of Imperial College London, has generated quite a bit of interest both in the media and among historians.  As Julius Caesar has always been one of my research interests, I contacted Dr. Ashrafian and requested a copy of the full article, after reading a synopsis in the mainstream media.

In the article, I learned that the medical community has, in the past, relied on only two episodes of Caesar falling, one at Cordoba and another at Thapsus, along with ancient sources refering to Caesar as having the "falling sickness", as the basis for acceptance of the diagnosis of epilepsy.  Drs. Galassi and Ashrafian point out that an analysis of the symptoms indicates that cerebrovascular insults and stroke should be considered, especially in view of other behavioral symptoms reported by the ancient sources.

"Caesar also suffered from other symptoms including depression and personality changes (exampled by emotional lability when listening to a moving oration by Cicero), which may also be consistent with cerebrovascular disease." - Francesco M. Galassi,  Hutan Ashrafian, Has the diagnosis of a stroke been overlooked in the symptoms of Julius Caesar?, Neurological Sciences, March 2015

The researchers go on to point out that Caesar's father and great grandfather had both died suddenly without apparent cause.

"This has been explained by some in terms of SUDEP (sudden unexpected death in epilepsy); however, these events can be more readily associated with the cardiovascular complications of stroke episode or a lethal myocardial infarction. Even if Caesar participated in an active lifestyle and may have benefited from an environmental background of a Mediterranean diet, there is the added possibility of genetic predisposition towards cardiovascular disease." Francesco M. Galassi,  Hutan Ashrafian, Has the diagnosis of a stroke been overlooked in the symptoms of Julius Caesar?, Neurological Sciences, March 2015

I think the researchers make very important points but I thought it would be even more illuminating to examine a more extensive case history.  Since we don't have a lot of information about Caesar's symptoms in the ancient sources, I decided to examine the much more detailed information we have, thanks to Nicolaus of Damascus and Suetonius, about the health of Augustus, since he, too, was said to have the "falling sickness" and was a blood relative of Caesar.

Augustus as Pontifex Maximus (High Priest).
Photographed at the Palazzo Massimo venue
of the 
National Museum of Rome, Rome, Italy
by Mary Harrsch 
© 2009

Caesar had only two siblings, sisters, both named Julia.  Sadly, little is known about either Julia so we have no definitive health information about them.  Julia the Younger married Marcus Atius Balbus and had either three or two daughters (depending on which source you read).  Her second daughter named Atia married Gaius Octavius and bore him a son, Octavian (later called the emperor Augustus) and a daughter named Octavia the Younger.

We know from the ancient sources that Octavian, like Caesar, was thought to have the "falling sickness".  We also know that his sister, Octavia, was said to have "fainting episodes".

Although most women, including Octavia, were practically ignored by ancient historians, Aelius Donatus, in his Life of Virgil, recalls at least one of Octavia's "fainting episodes.

"...Virgil recited three whole books [of his Aeneid] for Augustus: the second, fourth, and sixth--this last out of his well-known affection for Octavia, who (being present at the recitation) is said to have fainted at the lines about her son, "… You shall be Marcellus" [Aen. 6.884]. Revived only with difficulty, she sent Virgil ten-thousand sesterces for each of the verses."

Marcellus was Octavia's son who had recently died suddenly at a very young age.  Although Octavia may have had a simple fainting episode due to her intense grief, the fact that she was "revived only with difficulty" points to a more serious underlying health issue.

So, we appear to have two siblings that both suffer periods of unconsciousness.

Augustus had only a single daughter, Julia.  Julia was first married  to her first cousin, Marcellus (Octavia's son by her first husband, Gaius Claudius Marcellus Minor). Marcellus died two years later and the union produced no children - probably very fortunate since the couple had parents on both sides with possible seizure issues).

Then Julia was married to Marcus Vipsanius Agrippa and bore five children. One of them, Vipsania Agrippina would become the mother of the Emperor Gaius (Caligula) when she married Germanicus, Octavia's grandson. (those afflicted family lines cross again!)

Marcus Vipsanius Agrippa.  Photographed at The Musée du Louvre in Paris, France by
Mary Harrsch 
© 2008
Octavia, Augustus' apparently afflicted sister, had two children with her second husband, Marc Antony - Antonia the Elder who became grandmother to the Emperor Nero, and Antonia the Younger who was mother to the Emperor Claudius, grandmother to the Emperor Gaius (Caligula) and the great-grandmother to the Emperor Nero.  The ancient sources refer to all of these Julio-Claudian emperors as having the "falling sickness".

Research has shown that heart defects like atrial septal defect, a hole between the two upper chambers of the heart, can be inherited by successive generations within a family group.  It has also been shown that such defects can be transmitted through multifactorial inheritance (just like epilepsy), not just simply through the Mendelian Law of Dominance, the expression of a dominant or combination of recessive genes.

"When the defect is determined by a single gene difference, the risk to the unborn can be predicted from the Mendelian laws and does not change with successive children, but in a multifactorial system, the risk to the unborn increases with the number of relatives affected." - James J. Nora, M.D., Dan G. McNamara, M.D., and F. Clarke Fraser, M.D., Ph.D., Hereditary Factors in Atrial Septal Defect, Circulation Vol. XXXV, March 1967.

The study referenced above focused on atrial septal defects because it is the most common congenital heart defect encountered in adults.  Untreated atrial septal defect in adults is characterized by shortness of breath with minimal exercise (because of lower than normal oxygen levels in the lungs), congestive heart failure, and/or cerebrovascular accident (stroke).

Atrial septal defect.  Image courtesy of Wikimedia Commons.
Stroke results in an individual with ASD when a blood clot forms in a vein, dislodges and enters the arterial system rather than traveling to the lungs as it would in an individual with a normal dividing wall (interatrial septum) between the two upper chambers of the heart. This can cause any phenomenon that is attributed to acute loss of blood to a portion of the body, including cerebrovascular accident (stroke), infarction of the spleen or intestines, or even a distal extremity (i.e., finger or toe).  This is known as a paradoxical embolus because the clot material paradoxically enters the arterial system instead of going to the lungs.

So, with a heart defect and associated cerebrovascular accidents in mind, let's see what Octavian's health history reveals.

Like Caesar, Octavian lost his father from unexplained sudden death at a relatively young age.  His father, like Caesar's father, also appeared to be physically robust just prior to sudden death.

Portrait head thought to be Gaius Octavius.
Image courtesy of Wikimedia Commons.
"Macedonia fell to his [Gaius Octavius'] lot at the end of his praetorship; on his way to the province, executing a special commission from the senate, he wiped out a band of runaway slaves, refugees from the armies of Spartacus and Catiline, who held possession of the country about Thurii.  In governing his province he showed equal justice and courage; for besides routing the Bessi and the other Thracians in a great battle, his treatment of our allies was such, that Marcus Cicero, in letters which are still in existence, urges and admonishes his brother Quintus, who at the time was serving as proconsular governor4 of Asia with no great credit to himself, to imitate his neighbour Octavius in winning the favour of our allies."

While returning from Macedonia, before he could declare himself a candidate for the consulship, he died suddenly..." - Suetonius, The Lives of the Caesars, The Life of Augustus, 3:1

We already know that Octavian's grandmother's father (Julius Caesar's father) suffered sudden unexplained death as did her great great grandfather.  We have no health history for his mother or his grandmother but we do know from modern research that heart defects are expressed more often in females than males so there is a strong possibility that his mother and/or his grandmother inherited some form of defect from their fathers.

 The degree of debilitation in Octavian's case, if caused by an inherited cardiac-related condition, was compounded by his own father's probable predisposition to a heart disorder as well as an inherited condition from Caesar's father through Caesar's sister to Octavian's mother, Atia.

Then, when we examine the symptoms recorded by Augustus' biographers, particularly Nicolaus of Damascus and Suetonius, we find numerous suggestions of a cardiac-related condition resulting in pathology from apparent cerebrovascular accidents.

At the age of 14, Octavian donned the toga virilis and was immediately elected to the college of priests because of the death of Lucius Domitius.  But contemporary biographer Nicolaus of Damascus reports that Octavian's mother, Atia, watched over him closely and took care of him as if he was still a child.

Preparations for a Roman ritual sacrifice depicted on Trajan's Column in Rome.
Photographed by Mary Harrsch.  © 2009.
"He entered the Forum, aged about fourteen, to put off the toga praetextata and assume the toga virilis, this being a token of his becoming registered as a man. Then while all the citizens looked upon him, because of his comeliness and very evidently noble descent, he sacrificed to the gods and was registered in the sacred college in place of Lucius Domitius, who had died. The people indeed had very eagerly elected him to this position. Accordingly, he performed the sacrifice, adorned with the toga virilis and at the same time the honors of a very high priestly office."

"Nevertheless, though he was registered as of age according to law, his mother would not let him leave the house other than as he did before, when he was a child, and she made him keep to the same mode of life and sleep in the same apartment as before. For he was of age only by law, and in other respects was taken care of as a child." - Nicolas of Damascus, Life of Augustus, 4.

This could be an example of a smothering parent but we see that Octavian also seemed to avoid climbing steep stairs:

"He went to the temples on the regular days, but after dark on account of his youthful charm, seeing that he attracted many women by his comeliness and high lineage; though often tempted by them he seems never to have been enticed. Not only did the watchful care of his mother, who guarded him and forbade his wandering, protect him, but he too was prudent now that he was advancing in age. During the Latin festival when the consuls had to ascend the Alban Mount to perform the customary sacrifices, the priests meanwhile succeeding to the jurisdiction of the consuls, Octavius sat on the Tribunal in the center of the forum." -  Nicolaus of Damascus, Life of Augustus, 4.

When Caesar returned from Egypt and Syria and was planning his African campaign in Libya, Octavian wanted to go with him.

Triumphs of Caesar by Andrea Mantegna, Italian, circa 1485-1494
"Caesar had by this time completed the wars in Europe, had conquered Pompey in Macedonia, had taken Egypt, had returned from Syria and the Euxine Sea, and was intending to advance in to Libya in order to put down what was left of war over there; and Octavius wanted to take the field with him in order that he might gain experience in the practice of war. But when he found that his mother Atia was opposed he said nothing by way of argument but remained at home. It was plain that Caesar, out of solicitude for them, did not wish him to take the field yet, lest he might bring on illness to a weak body through changing his mode of life and thus permanently injure his health. For this cause he took no part in the expedition. " - Nicolaus of Damascus, Life of Augustus, 6.

When Caesar returned from Africa, he asked Octavian to accompany him to many social functions including temple sacrifices, theater performances and banquets as if Octavian was his own son.  But again, Octavian was striken with serious illness:

 "Caesar wished Octavius to have the experience of directing the exhibition of theatrical productions (for there were two theaters, the one Roman, over which he himself had charge, and the other Greek). This he turned over to the care of Octavius. The latter, wishing to exhibit interest and benevolence in the matter, even on the hottest and longest days, never left his post before the end of the play; with the result that he fell ill, for he was young and unaccustomed to toil. Being very ill, every one felt considerable apprehension regarding him, lest a constitution such as his might suffer some mishap, and Caesar most of all. Accordingly, every day he either called himself and encouraged him or else sent friends to do so, and he kept physicians in continuous attendance. On one occasion word was brought to him while he was dining that Octavius was in a state of collapse and dangerously ill. He sprang up and ran barefooted to the place where the patient was, and in great anxiety and with great emotion questioned the physicians, and he sat down by the bedside himself. When Octavius' full recovery was brought about, he showed much joy." - Nicolaus of Damascus, Life of Augustus, 9.

When Caesar planned to go to Spain to engage the sons of his former rival Pompey, he tells Octavian, who is still weak, to join him when he is well enough.

"While Octavius was convalescent, still weak physically though entirely out of danger, Caesar had to take the field on an expedition in which he had previously the intention of taking the boy. This however he could not now do on account of his attack of sickness. Accordingly, he left him behind in the care of a number of persons who were to take particular charge of his mode of life; and giving orders that if Octavius should grow strong enough, he was to follow him, he went off to the war. The eldest son of Pompeius Magnus [Gnaeus Pompeius] had got together a great force in a short time, contrary to the expectations of everyone, with the intention of avenging his father's death, and, if possible, of retrieving his father's defeat. Octavius, left behind in Rome, in the first place gave his attention to gaining as much physical strength as possible, and soon he was sufficiently robust." -  Nicolaus of Damascus, Life of Augustus, 10.

However, when Octavian returns to Rome, his health still seems to be problematic and he seems to avoid physical exertion.

"Octavius lived soberly and in moderation; his friends know of something else about him that was remarkable. For an entire year at the very age at which youths, particularly those with wealth, are most wanton, he abstained from sexual gratification out of regard for both his voice and his strength." -  Nicolaus of Damascus, Life of Augustus, 15.

Assassination of Julius Caesar by William Holmes Sullivan (1836-1908).
When Caesar is assassinated, Octavian takes up the challenge to avenge his adopted father and assume his rightful place as heir to both Caesar's fortunes and ambitions.  But his health is still fragile.

At the battle of Mutina when Octavian's forces beseiged Decimus Brutus, one of the conspirators in the assassination of Caesar, Marc Antony claims " he took to flight and was not seen again until the next day, when he returned without his cloak and his horse."  Although this incident could have been a loss of nerve, his following actions do not support a lack of courage.

A Roman aquilifer carrying an eagle standard.
Image courtesy of Jorl Avlis © 2014

"but in that which followed all agree that he played the part not only a leader, but of a soldier as well, and that, in the thick of the fight, when the eagle-bearer of his legion was sorely wounded, he shouldered the eagle and carried it for some time. " - Suetonius, The Lives of the Caesars, The Life of Augustus, 10:1

Although Suetonius also claims Augustus did not lack the gift of speaking offhand without preparation, he points out that after the battle of Mutina the young Octavian never again addressed the people or soldiers without reading from a written manuscript.

"Even his conversations with individuals and the more important of those with his own wife Livia, he always wrote out and read from a note-book, for fear of saying too much or too little if he spoke offhand."  Suetonius, The Lives of the Caesars, The Life of Augustus, 84:1

Illness struck him down again at the battle of Philippi:

"Then, forming a league with Antony and Lepidus, he finished the war of Philippi also in two battles, although weakened by illness, being driven from his camp in the first battle and barely making his escape by fleeing to Antony's division." -  Suetonius, The Lives of the Caesars, The Life of Augustus, 13:1

Plutarch gives a more thorough description, indicating Octavian was so ill he had to be carried on a litter:

"And Octavius, as he himself tells us in his Commentaries, in consequence of a vision which visited one of his friends, Marcus Artorius, and ordered that Octavius should rise up from his bed and depart from the camp, barely succeeded in having himself carried forth, and was thought to have been slain.  For his litter, when empty, was pierced by the javelins and spears of his enemies."  Plutarch, Parallel Lives, Brutus, 41:7

During the subsequent Sicilian War with Pompey's son, Sextus, Suetonius records that Octavian appears to have suffered a catatonic episode:

"...he defeated Pompey between Mylae and Naulochus, though just before the battle he was suddenly held fast by so deep a sleep that his friends had to awaken him to give the signal.  And it was this, I think, that gave Antony opportunity for the taunt: 'He could not even look with steady eyes at the fleet when it was ready for battle, but lay in a stupor on his back, looking up at the sky, and did not rise or appear before the soldiers until the enemy's ships had been put to flight by Marcus Agrippa.' -  Suetonius, The Lives of the Caesars, The Life of Augustus, 16:1

Although this episode is first described as Octavian being in an unusually deep sleep, the symptoms in Antony's taunt are more illuminating, clearly describing the unresponsive Octavian on his back with his eyes open.  Catatonia has been observed in individuals suffering from focal neurologic lesions, including strokes.  There was no mention of any convulsive activity.  Furthermore, ministrokes can resolve without intervention.  If Octavian's condition was caused by a sudden vascular ischemic event that was not accompanied by edema or hemorrhage, it could resolve itself within minutes and he could become once more, apparently fully functional.

But, these repeated occurrences of neurological events would not be without behavioral consequences.  As time passes and Octavian assumes the ultimate position of power over the Roman Empire, Octavian, now called Augustus, appears fickle in his administration of justice - sometimes extremely lenient while at other times totally without compassion and stubbornly inflexible.  He also became subject to sudden outbursts of immoderate speech and outright brutality.

"While he was triumvir, Augustus incurred general detestation by many of his acts. For example, when he was addressing the soldiers and a throng of civilians had been admitted to the assembly, noticing that Pinarius, a Roman knight, was taking notes, he ordered that he be stabbed on the spot, thinking him an eavesdropper and a spy. Because Tedius Afer, consul elect, railed at some act of his in spiteful terms, he uttered such terrible threats that Afer committed suicide.  Again, when Quintus Gallius, a praetor, held some folded tablets under his robe as he was paying his respects, Augustus, suspecting that he had a sword concealed there, did not dare to make a search on the spot for fear it should turn out to be something else; but a little later he had Gallius hustled from the tribunal by some centurions and soldiers, tortured him as if he were a slave, and though he made no confession, ordered his execution, first tearing out the man's eyes with his own hand." -  Suetonius, The Lives of the Caesars, The Life of Augustus, 27:3

Loss of impulse control and the ability to interpret other people's behaviors have been documented in modern studies of individuals who have suffered frontal lobe brain injury.

Octavian, who initially opposed the proscriptions of his opponents (the seizing of their property that was often accompanied by their deaths) favored by his fellow triumvirs, Antony and Lepidus, enforced proscriptions with greater severity than either of his colleagues.

"For while they could oftentimes be moved by personal influence and entreaties, he alone was most insistent that no one should be spared, even adding to the list his guardian Gaius Toranius, who had also been the colleague of his father Octavius in the aedileship." -  Suetonius, The Lives of the Caesars, The Life of Augustus, 27:1

Inflexibility in decision making has also been observed in studies of individuals who have suffered lesions in their frontal lobes.

Later, Augustus also appears to have demonstrated a heightened xenophobic response.  He fiercely opposed the grant of citizenship to any foreign resident or former slave:

Roman slave medallion.  Photographed at
the National Museum of Rome in the
remains of the Terme di Diocleziano
(Baths of Diocletian), Rome, Italy by
Mary Harrsch.  © 2005
"Considering it also of great importance to keep the people pure and unsullied by any taint of foreign or servile blood, he was most wary of conferring Roman citizenship and set a limit to manumission. When Tiberius requested citizenship for a Grecian dependent of his, Augustus wrote in reply that he would not grant it unless the man appeared in person and convinced him that he had reasonable grounds for the request; and when Livia asked it for a Gaul from a tributary province, he refused, offering instead freedom from tribute, and declaring that he would more willingly suffer a loss to his privy purse than the prostitution of the honour of Roman citizenship.  Not content with making it difficult for slaves to acquire freedom, and still more so for them to attain full rights, by making careful provision as to the number, condition, and status of those who were manumitted, he added the proviso that no one who had ever been put in irons or tortured should acquire citizenship by any grade of freedom." - -  Suetonius, The Lives of the Caesars, The Life of Augustus, 40:3

When Rome suffered a grain shortage, Augustus ejected foreigners and slaves.

Once indeed in a time of great scarcity when it was difficult to find a remedy, he expelled from the city the slaves that were for sale, as well as the schools of gladiators, all foreigners with the exception of physicians and teachers, and a part of the household slaves; -  Suetonius, The Lives of the Caesars, The Life of Augustus, 42:3

Augustus also allowed superstition to rule much of his life.  Augustus would delay journeys, decisions or public addresses if it began to rain or he accidentally put the left shoe on first in the morning upon rising instead of the right, considering it a bad omen.

Increased paranoia has also been recorded in studies of brain injury.

Where as a young man, Octavian was sexually circumspect, as the years passed he became sexually wanton, so much so even Antony, no stranger to a promiscuous lifestyle, questioned the dramatic change in Octavian's behavior.
Portrait head thought to be Marc Antony from Egypt.
Photographed at the Brooklyn Museum in
Brooklyn, New York by Mary Harrsch 
 © 2014

"That he was given to adultery not even his friends deny, although it is true that they excuse it as committed not from passion but from policy, the more readily to get track of his adversaries' designs through the women of their households. Mark Antony charged him, besides his hasty marriage with Livia, with taking the wife of an ex-consul from her husband's dining-room before his very eyes into a bed-chamber, and bringing her back to the table with her hair in disorder and her ears glowing; that Scribonia was divorced because she expressed her resentment too freely at the excessive influence of a rival; that his friends acted as his panders, and stripped and inspected matrons and well-grown girls, as if Toranius the slave-dealer were putting them up for sale.  Antony also writes to Augustus himself in the following familiar terms, when he had not yet wholly broken with him privately or publicly: 'What has made such a change in you? Because I lie with the queen? She is my wife. Am I just beginning this, or was it nine years ago? What then of you — do you lie only with Drusilla? Good luck to you if when you read this letter you have not been with Tertulla or Terentilla or Rufilla or Salvia Titisenia, or all of them. Does it matter where or with whom you take your pleasure?'" -  Suetonius, The Lives of the Caesars, The Life of Augustus, 69:1

"Hypersexuality is a rare but well recognised sequela of brain injury . It has been defined as the subjective experience of loss of control over sexuality; and consists of increased need or intense pressure for sexual gratification." - PO Eghwrudjakpor,  AA Essien, Hypersexual Behavior Following Craniocerebral Trauma An Experience with Five Cases

In addition to behavioral aberrations, Augustus also developed physical impairments specific to one side of his body or the other.

"He was not very strong in his left hip, thigh, and leg, and even limped slightly at times; but he strengthened them by treatment with sand and reeds. He sometimes found the forefinger of his right hand so weak, when it was numb and shrunken with the cold, that he could hardly use it for writing even with the aid of a finger-stall of horn."  -  Suetonius, The Lives of the Caesars, The Life of Augustus, 80:1

Problems with weakness on his left side definitely point to a cerebrovascular event.  Even the disability of his right forefinger could be attributed to a paradoxical embolus.

Augustus continued to be ravaged by illness throughout his life even though, amazingly, he micromanaged Rome's burgeoning empire and presided over a period of great prosperity that has become known as the Pax Romana.

"It chanced that at the time of the games which he had vowed to give in the circus, he was taken ill and headed the sacred procession lying in a litter;"   -  Suetonius, The Lives of the Caesars, The Life of Augustus, 43:5

"He was sometimes absent for several hours, and now and then for whole days, making his excuses and appointing presiding officers to take his place. " -  Suetonius, The Lives of the Caesars, The Life of Augustus, 45:1

"In the course of his life he suffered from several severe and dangerous illnesses, especially after the subjugation of Cantabria [about age 44], when he was in such a desperate plight from abscesses of the liver, that he was forced to submit to an unprecedented and hazardous course of treatment. Since hot fomentations gave him no relief, he was led by the advice of his physician Antonius Musa to try cold ones." Suetonius, The Lives of the Caesars, The Life of Augustus, 81:1

Could the "abscesses of the liver" actually be an infarction of the spleen or intestines from a paradoxical embolism?

The severity of the illness Augustus suffered after the Cantabrian war is hinted at indirectly when Suetonius points out that Augustus wrote thirteen books of his autobiography describing the events of his life up to the Cantabrian war but no farther.  Did he simply get tired of writing or couldn't he remember key experiences or the order in which the experiences occurred after that event?

"...studies suggest that patients with lateral PFC [prefrontal cortex] damage, especially to the DLPFC [dorsolateral prefrontal cortex], are unable to organize learned information to facilitate their recall. It has been proposed that most of these deficits result from a failure of the PFC to inhibit unwanted information or to select among competing memories. As a result, recently activated memories can interfere with the ability to retrieve more distant memories (Shimamura et al., 1995 and Warrington and Weiskrantz, 1974)." - Sara M. Szczepanski, Robert T. Knight, Insights into Human Behavior from Lesions to the Prefrontal Cortex

"He experienced also some disorders which recurred every year at definite times; for he was commonly ailing just before his birthday [23 September]; and at the beginning of spring he was troubled with an enlargement of the diaphragm, and when the wind was in the south, with catarrh [excess mucus] Hence his constitution was so weakened that he could not readily endure either cold or heat." Suetonius, The Lives of the Caesars, The Life of Augustus, 81:2

Of course everyone's life is littered with illness to some degree.  But, I think Augustus clearly represents an individual with a recurring pattern of overall physical weakness indicative of a vascular deficit combined with symptoms of cerebrovascular accident.

In Summary:

We began our evaluation of Augustus' health with the consideration of a pedigree including multiple ancestors on his mother's side and his father who suffered sudden unexplained death.  We find a childhood plagued with prolonged illness that made him so physically weak that his activities had to be curtailed.  We have evidence he avoided stairs and sexual activity in early adulthood when his hormones would have been at their peak.

We read reports of unexplained disappearances and what appears to be a serious loss of short term memory, continued severe weakness that required him to be carried on a litter and even an episode of catatonia.

Then we learn about changes in his behavior that included loss of impulse control, loss of the ability to interpret other people's behavior accurately, changes in sexual behavior, heightened paranoia as expressed in increased xenophobia and superstition and inconsistent decision making.

We also know from the historical record that other descendants of Augustus' mother appeared to have suffered serious physical and/or neurological issues, including the emperors Gaius (Caligula), Nero and Claudius as well as Claudius' son, Britannicus.

In a 1958 study, A. Esser describes the routes a condition subject to multifactorial inheritance could take in the Julio-Claudians.  It was quoted in an article published in October 2004 by Epilepsy & Behavior.  Although he was discussing epilepsy, the same routes could be followed by congenital heart defects like atrial septal defect.

"Esser had provided interesting blood connections between the three members of the Julio-Claudian family with seizures: (1) Julius Caesar, (2) Caligula, and (3) Britannicus. Julius' sister Julia is the ancestor of both Caligula and Britannicus. There were three major blood streams to Caligula. The first is through Julius' sister, Julia, to Atia, Octavianus (Augustus), to (another) Julia, Agrippina Major, and finally to Caligula. The second is also through Octavianus but then to Drusus I and Germanicus to Caligula. The third is also through sister Julia and Atia, but then to Octavia minor, to Antonia Minor, to Germanicus, and finally to Caligula. The latter Antonia Minor also provides one of the paths to Britannicus through Claudius, his father. The second path to Britannicus is also through Octavia Minor, through Antonia Major to Domita Lepida, to Messalina, and finally to Britannicus. These complex paths would argue for a recessive mode of inheritance. In the latter paths both Octavianus and his sister Octavia Minor are grandchildren of Julius Caesar's sister. Octavianus had a problem with “deep sleep” and his sister, Octavia Minor, with “fainting attacks,” but nothing more is known about these symptoms to qualify them as definite epileptic phenomena. The “fainting attacks” of Octavia minor, however, are suspicious for possible seizure phenomena." - John R. Hughes, Dictator Perpetuus: Julius Caesar - Did he have seizures? If so, what was the etiology?, Epilepsy & Behavior, Vol 5, Issue 5, October 2004.

Although seizures may have occured, especially in view of increased brain damage with each stroke episode, I believe the ancient sources provide enough symptoms consistent with cardiac dysfunction and related cerebral accidents to support Drs. Galassi and Ashrafian in their proposal that cardiac dysfunction and stroke eventually produced the physical and psychological changes expressed in Julius Caesar (and Augustus).


Galassi, F., & Ashrafian, H. (2015). Has the diagnosis of a stroke been overlooked in the symptoms of Julius Caesar? Neurological Sciences.

Cawthorne, T. (1958). Julius Cæsar and the Falling Sickness. Proceedings of the Royal Society of Medicine, 51(1), 27-30.

Hughes, J. (2004). Dictator Perpetuus: Julius Caesar?Did He Have Seizures? If So, What Was The Etiology? Epilepsy & Behavior, 5(5), 756-764.

Nora, J., Mcnamara, D., & Fraser, F. (1967). Hereditary Factors in Atrial Septal Defect. Circulation, XXXV, 448-456. Retrieved April 20, 2015.

American Journal of Neuroradiology (Focal Neurologic Deficit)

Szczepanski, S., & Knight, R. (2014). Insights into Human Behavior from Lesions to the Prefrontal Cortex. Neuron, 83(5), 1002–1018.

Fowler, M., & McCabe, P. C. (2011). Traumatic brain injury and personality change. Bethesda: Retrieved from http://search.proquest.com/docview/867665184?accountid=14698

Eghwrudjakpor, P., & Essien, A. (2008). Hypersexual Behavior Following Craniocerebral Trauma An Experience with Five Cases. The Libyan Journal of Medicine, 3(4), 192–194. doi:10.4176/080908

Catalan J, Singh A. Hypersexuality revisited. Journal of Foresnsic Psychiatry and Psychology. 1995;6(2):255–258.

Suetonius, G. (n.d.). The Life of Augustus. The Lives of the Caesars.

Suetonius, G. (n.d.). The Life of Nero. The Lives of the Caesars.

Nicolas of Damascus. (n.d.). The Life of Augustus.

Donatus, A. (n.d.). Life of Virgil.

Plutarch, L. (n.d.). Brutus. Parallel Lives.

Thursday, October 7, 2010

"Grotesque" Imagery of Amarna Art Religion Not Reality

A history resource article by  © 2010

Small statue of Ahkenaten wearing the blue crownImage of small statue of Akhenaten  via Wikipedia
I was researching Egypt's 18th dynasty in the course of writing a book review and came across the official journal article detailing the results of a medical analysis recently done on mummies either identified or tentatively identified as members of the 18th dynasty.  The report is fascinating, although laymen may need to keep dictionary.com handy as it is written for the medical professional members of the American Medical Association.

I had heard that the studies had definitely concluded that Pharaoh Tutankhamun was not murdered but probably died as the result of a severe infestation of malaria.  But this report goes much further and discounts most pathological speculations about his father, the "heretic" pharaoh, Akhenaten, as well.

Replica of the bust of Queen Nefertiti 18th Dy...A reproduction of the famous bust of Nefertiti photographed at the Rosicrucian Egyptian Museum by Mary Harrsch (mharrsch) via Flickr
 Macroscopic and radiological inspection of the mummies did not show specific signs of gynecomastia, craniosynostoses, Antley-Bixler syndrome or deficiency in cytochrome P450 oxidoreductase, Marfan syndrome, or related disorders (eAppendix, Table 2). Therefore, the particular artistic presentation of persons in the Amarna period is confirmed as a royally decreed style most probably related to the religious reforms of Akhenaten.  It is unlikely that either Tutankhamun or Akhenaten actually displayed a significantly bizarre or feminine physique.

It is important to note that ancient Egyptian kings typically had themselves and their families represented in an idealized fashion. A recent radiographic examination of the Nefertiti bust in the Berlin Museum illustrates this clearly by showing that the original face of Nefertiti, present as a thin layer beneath the outer surface, is less beautiful than that represented by the artifact.33 Differences include the angles of the eyelids, creases around the corners of the mouth on the limestone surface, and a slight bump on the ridge of  the nose.34 Thus, especially in the absence of morphological justification, Akhenaten’s choice of a “grotesque” style becomes even more significant. - Ancestry and Pathology in King Tutankhamun's Family, Journal of the American Medical Association
I see the researchers also did exhaustive skull studies and apparently the elongated skulls of Akhenaten and Nefertiti's daughters portrayed in Amarna art were also exaggerated. Unlike the Mayans, the Egyptians may have admired an unusually shaped head but they did not attempt skull binding to create it.

Related articles by Zemanta
Akhenaten: Egypt's False Prophet   Amarna Sunset: Nefertiti, Tutankhamun, Ay, Horemheb, and the Egyptian Counter-Reformation   The Amarna Letters

Tuesday, February 3, 2009

Alexander the Great's Mysterious Death: Poisoned wine or Intestinal Bug?

A history resource article by  © 2015
Head of Alexander the Great photographed at
The Capitoline Museum in Rome, Italy by
Mary Harrsch  © 2005.

I noticed that a program entitled "Alexander the Great's Mysterious Death" on the Discovery Channel put forward the hypothesis that Alexander died from an accidental overdose of hellebore, a poisonous plant used to induced vomiting in ancient times.

[Alexander the Great, Photographed at the Capitoline Museum, Rome, Italy by Mary Harrsch © 2005 ]

Back in 1998, however, a group of doctors gathered for a clinical pathology conference at the University of Maryland Medical Center expressed their belief that Alexander was killed by an intestinal bug:
Alexander the Great, who ruled much of the ancient world until his death in 323 B.C., was conquered at age 32 not by an enemy, but possibly by a tiny intestinal bug. In an analysis based on available historical records, physicians at the University of Maryland Medical Center believe that Alexander was the victim of typhoid fever.

Their analysis, titled, "A Mysterious Death," is published in the June 11 issue of the New England Journal of Medicine. The most popular theories among historians previously have been that Alexander was poisoned or had died of malaria.

In the week before he died, historical accounts say Alexander the Great had chills, sweats, exhaustion and high fever, all of which are typical symptoms of certain infectious diseases, including typhoid fever.

"He was also described as having severe abdominal pain, causing him to cry out in agony," says David W. Oldach, an infectious disease expert at the University of Maryland Medical Center and lead author of the article.

"That was an important clue, because untreated typhoid fever can lead to perforation of the bowel and may have been the reason for his abdominal pain," according to Dr. Oldach, who is also an assistant professor of medicine at the University of Maryland School of Medicine.

"My discussions with Dr. Oldach and his colleagues caused me to change my mind about what caused the death of Alexander the Great," says Eugene N. Borza. Ph.D., professor emeritus of ancient history who taught for 31 years at Penn State University. Dr. Borza, who is also an author of the New England Journal article, previously thought that malaria caused Alexander's demise.

A curious symptom described in ancient accounts is that Alexander's body did not begin to decay for at least several days after his death. Dr. Oldach says while that defies reason, those around him may have gotten that impression because of another complication of typhoid fever, called ascending paralysis. It is a neurological problem that starts with the feet and moves up the body, paralyzing muscles and slowing down breathing. It can make a person look dead, even if he is not. Alexander may have been in that state for a few days before he died.
The death of Alexander the Great.  Courtesy of History.com.
 Accounts of the death were not consistent with poisoning, although Dr. Borza says that has been a popular belief. "It was an ancient conspiracy theory. People have often suspected a conspiracy when a famous young person dies unexpectedly." Dr. Borza says ancient Greeks who didn't succumb to disease as a child or a battlefield wound often lived into their 70's, because of a healthy diet and constant physical activity.
The New England Journal of Medicine article is believed to be the first collaboration between medical scientists and an historian to answer an ancient question about what caused a famous historical figure to die. Dr. Borza says the earliest surviving accounts about Alexander's death available today were written three centuries after he died, so there was not a lot of information to go on.

"Even so, we found out that much of the scant information we do have is credible, because it makes sense to the medical community. It is important for us to be able to validate the evidence and set the record straight. As historians, that's what we try to do," says Dr. Borza.

For his analysis, Dr. Oldach also had to rely on historical medical accounts of what happens when typhoid fever goes untreated with antibiotics, which did not become available until the 1950's. U.S. physicians today rarely witness untreated patients in the late stages of typhoid fever.

Typhoid fever comes from salmonella typhi, an organism that lives only in humans and can be spread by contaminated water or because of poor hygiene.

Update: 2/18/2015:  

In January 2014 an article was published in the Journal of Clinical Toxicology.  Co-authored by the University of Otago 's Dr. Leo J. Schep, from the National Poisons Centre in New Zealand, the researchers theorized that Alexander was killed by a toxic wine created using a fermented form of Veratrum album (also known as white hellebore) sometimes used to induce vomiting.  The study's authors detailed the potential deadliness of the plant in the study abstract:

"Veratrum album flower" by Alpsdake.
Courtesy of  Wikimedia Commons.

Veratrum poisoning is heralded by the sudden onset of epigastric and substernal pain, which may also be accompanied by nausea and vomiting, followed by bradycardia and hypotension with severe muscular weakness.

"Exposure to extracts from this plant causes clinical effects similar to [Alexander's] reported signs and symptoms," Schep observes, "Of note was the duration of symptoms, which could continue for more than 12 days if intoxicated patients are not treated."

Personally, I think the analysis by the pathologists in Maryland appears more credible (to me) since they evaluated the overall reported symptoms as detailed in fragments of the ancient sources rather than focus on the relatively immediate reactions Alexander experienced at a banquet with his generals that has long been viewed historically as suspect.  If Alexander's digestive tract was  already severely compromised (by a pathogen like typhoid), his consumption of normal wine at the banquet  could have triggered an acute episode of abdominal distress. Without his remains, however, I guess we will never know!