science notes

eware, for this man has a diseased brain!” So wrote Friedrich Nietzsche's first biographer, Dr Paul Julius Möbius^[3]. Nietzsche's own sister Elisabeth deliberately linked his ideas to Adolf Hitler, who appropriated his idea of the Übermensch and twisted it into the idea of a master race. With biographers like this, who needs character assassins?

It seems there are two types of articles about Nietzsche: those from people who hate him, and those from people who really hate him. Then there's the story of Nietzsche's early-onset dementia, which started when he was 44, that was supposedly due to tertiary syphilis.

Nietzsche suffered from severe migraine since childhood, which might seem to rule out syphilis as a cause. However, there is such a thing as congenital syphilis, in which the Treponema pallidum spirochete is passed to the fetus via the placenta. But doctors examining Nietzsche's medical records have concluded that the evidence is absolutely inconsistent with syphilis.

Tertiary syphilis, which occurs in one-third of untreated cases, is well known to cause skin lesions, periostitis or osteitis with deep bone pain, and, most importantly, parenchymatous neurosyphilis and tabes dorsalis.

Parenchymatous neurosyphilis develops from chronic meningoencephalitis over a period of 15–20 years as the spirochete attacks the brain matter. The symptoms are headaches, insomnia, memory loss, and sometimes disinhibition, mania and delusions of grandeur. Tabes dorsalis, or syphilitic myelopathy, is a form of demyelination of the spinal cord: degeneration of the nerve roots and posterior column (an ascending white matter sensory pathway on the spinal cord), which causes locomotor ataxia. Symptoms are intense leg and back pain, gait ataxia, and hyperesthesia. Patients have characteristic sad faces and inability of the pupil to contract on exposure to light (known as Argyll Robertson pupil).

Standard diagnostic manuals like The Merck Manual consider the Argyll Robertson pupil a strong clue of tertiary syphilis. Since T. pallidum cannot be cultured in the laboratory, a definitive diagnosis requires darkfield identification of the spirochete, serological tests and treponemal antibody tests. None of these were available in Nietzsche's day.

The Leonard Sax Article

Britain's Telegraph newspaper cited an article by Leonard Sax who concluded ^[4] that it was cancer, not syphilis, that did Nietzsche in, and that the syphilis rumor was a posthumous smear invented by anti-Nazis.

Sax's article says that his doctors in Basel, Switzerland found none of the five distinctive signs of paretic syphilis: an expressionless face, hyperactive tendon reflexes, tremor of the tongue and facial muscles, impairment of handwriting, and slurred speech. He wrote: “His facial expressions remained vivid and evocative; his reflexes were normal; tremor was not present; his handwriting in the weeks and months after his collapse was at least as good as it had been in previous years; and his speech was fluent.”

Sax quotes R. J. Hollingdale, who stated in his 1999 biography of Nietzsche: “Richard Blunck reproduces evidence which makes it impossible to doubt that Nietzsche was treated for a syphilitic infection by two Leipzig doctors during 1867.” It is not so, says Sax: Blunck uncritically lifted this from an obscure and biased book by Wilhelm Lange-Eichbaum^[5], who created this rumor to blame Nietzsche for Nazism.

According to Sax, the diagnosis was made solely on the basis of the sluggish contraction of his right pupil, which Nietzsche had since early childhood (and may have contributed to his headaches), and his grandiose delusions (which indicate that the physician was not aware that Nietzsche was a philosopher).

Sax points out that migraines (which Nietzsche had from age nine) and tumors can also interfere with pupillary contraction. He suggests a slow-growing retro-orbital meningioma, a tumor of the membranous layers surrounding the brain. This is consistent with the fact that Nietzsche's migraines were mostly on the right side, a persistent headache confined to one side being a classic sign of tumor or other organic disease.

CADASIL

All recent re-evaluations of the evidence unequivocally reject the diagnosis of neurosyphilis as inconsistent with the evidence. Lampros Perogamvros and colleagues in Switzerland ^[6], summarizing the previous diagnoses, made a convincing case that while Nietzsche's hypomanic/manic symptoms contributed to his grandiose writing, the previous claims of frontotemporal dementia^[7], meningioma^[4,8], schizophrenia^[9] and mitochondrial encephalomyopathy^[10], as well as neurosyphilis, are insufficient to explain the symptoms. The most likely diagnosis, they wrote, is Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL).

CADASIL is a an inherited autosomal dominant vascular microangiopathy caused by mutations on the Notch3 gene localized on chromosome 19p13.1. It is a slowly progressive disease that worsens in a series of strokes. The symptoms are ^[11]:

• Exceptionally severe migraine, sometimes to the extent of causing hemiparesis.
• Recurrent ischemic strokes (multiple small infarcts, detectable on T1-weighted MRI), peaking at age 40–50.
• Psychiatric symptoms.
• Frontal lobe executive deterioration, followed by impairment of memory.
• Cognitive decline leading to dementia within 15–25 years of the first strokes.

T2-weighted MRI of CADASIL patients shows early diffuse symmetric temporopolar hyperintensities, which are pathognomonic for CADASIL. Later MRIs show extensive confluent hyperintensities showing non-amyloid and non-atherosclerotic arteriopathy. The arteriopathy is present throughout the body, including skin, muscle and peripheral nerves, but the symptoms are almost exclusively neurological. Most of the affected arterioles are in the cerebral white matter, and most of the infarcts occur there. Hence the term leukoencephalopathy.

In layman's terms this means the blood vessels in the brain are defective, with accumulation of extra granular material and then degeneration and fibrosis of blood vessels. Symptomatically it appears similar to familial early-onset Alzheimer's disease or frontotemporal dementia, but with more severe psychiatric symptoms. At the molecular level, it is a genetic defect in Notch3, a transmembrane receptor protein that gets cleaved by TACE and gamma-secretase—the same enzymes that cleave the amyloid precursor protein (APP) that is so important in Alzheimer's disease. Unlike APP, Notch3 is specific to vascular smooth muscle cells.

Perogamvros et al. say there is also evidence of Gastaut-Geschwind syndrome, which occurs in temporal stroke patients. It is characterized by emotionality, hypermoralism, obsessionalism, viscosity, religiosity, guilt, paranoia, hyposexuality, humorlessness, and philosophical interest. This isn't really a disorder, but a collection of character traits that have been observed in stroke and epilepsy patients.

Nietzsche definitely had some of those personality traits. But none of the aforementioned diseases by themselves can increase creativity or intellectual vigor. For that to occur, the brain would have to compensate, making repairs as it were, and overcompensating. This is something the brain might do, but we are only now beginning to understand it.

It should also be noted, though, that the period after a migraine finally disappears is, for many sufferers, a time of bliss and enormous outpourings of creativity, as a natural response to the cessation of excruciating pain. Nietzsche's writings were often done under similar circumstances, suggesting that his “mania” may be, in part, a state of relief which those who do not suffer from congenital migraines can only imagine.

Syphilis does not create genius

Whether you like his ideas or not, Nietzsche stands as a chilling reminder that once we're gone, our enemies can and will spread rumors about us, and we will be powerless to prevent it. But it's not just Nietzsche. Beethoven, Lincoln, van Gogh, Columbus, and dozens of others have gotten the same treatment. It's one thing to claim that these great men of history suffered from a widespread disease. It's another to suggest, as some popular writers have done, that it produced their greatness.

This discredits the very concept of genius. People merrily repeat the myths, happy in the knowledge that they are really just as smart as Nietzsche and just as talented as van Gogh, and the ideas they don't understand or which they find threatening may be safely ignored.

You might call it the Harrison Bergeron of ideas: it lets people comfortably believe that everyone is intellectually equal, merely because they exist—the very idea Nietzsche hated most.

As Nietzsche said, what doesn't kill you makes you stronger. But syphilis will kill you, and getting it will not make anyone, not even Nietzsche, smarter, stronger, funnier, more creative, or more fun, nor will it help anyone conquer the world or write great philosophy.

Nietzsche was way ahead of us. He died of complications from a disease that was not discovered until 55 years after his death. He flummoxed the herd mentality of both the Nazis and the anti-Nazis, and stumped two generations of diagnosticians until DNA technology finally revealed what drove him mad. Or maybe he just got lucky in being famous enough for Sax and others to take an interest. The herd instinct resuscitated his reputation. Wherever he is, looking down at us, or maybe looking up at us, with eternal flames of damnation licking his sides, I doubt he would appreciate the irony.

References

[1]. Not to be confused with the popular tune by António Carlos Jobim and Vinicius de Moraes.

[2]. According to Google, five other people thought of this joke before me, in one case referring to the Crazy Female Scientist Who Must Not Be Named.

[3]. Möbius PJ. Über das Pathologische bei Nietzsche. Wiesbaden: J. F. Bergmann, 1902: p. 103. (cited in Sax, ref. 4)

[4]. Sax, L. (2003). What was the cause of Nietzsche's dementia? J. Med. Biography 11, 47–54.

[5]. Nietzsche: Krankheit und Wirkung. Lettenbauer, Hamburg 1946.

[6]. Perogamvros L, Perrig S, Bogousslavsky J, Giannakopoulos P (2013) Friedrich Nietzsche and his Illness: A Neurophilosophical Approach to Introspection J. History of the Neurosciences 22, 174–182 abstract

[7]. Orth M, Trimble MR (2006). Friedrich Nietzsche's mental illness: General paralysis of the insane vs. frontotemporal dementia. Acta Psychiatr Scand 114, 439–445.

[8]. Owen, CM Schaller C, Binder DK (2007). The madness of Dionysius: a neurosurgical perspective on Friedrich Nietzsche. Neurosurgery 61, 626–632.

[9]. Danesh-Meyer, HV, Young J (2010). Friedrich Nietzsche and the seduction of Occam's razor. J. Clin. Neurosci. 17, 966–969.

[10]. Koszka C (2009): Friedrich Nietzsche (1844–1900): A classical case of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome? Journal of Medical Biography 17, 161–164.

[11]. Greenfield's Neuropathology, 8th ed, p. 146, Love S, Louis DN, Ellison DW eds, Hodder Arnold 2008.