Personality changes in persons with chronic brain infection
with C. pneumoniae (including Multiple Sclerosis)


David Wheldon FRCPath

(Note: this essay is concerned with the general widespread personality change which may occur independently of the anatomical site of the lesions in multiple sclerosis. The lesions themselves may cause character change very specific to the person with the disease. This essay does not treat with this.)

Stereotypic changes in personality in people with aggressive MS have long been recognized. Sometimes these personality changes continue within remissions; this happened with Sarah: long before Multiple Sclerosis was diagnosed I recognised that she was not herself even while she was able to walk for miles. To look back at those times is not easy. I was aware that I was looking at the very same mental state which I had seen in others with MS. Here is an excellent paper which examines this phenomenon, which is not accounted for by demyelination.
[Benedict, RHB et al., Personality Disorder in Multiple Sclerosis correlates with cognitive impairment. J Neuropsychiatry Clin Neurosci 2001; 13: 70 - 76.] These authors come to the conclusion that this personality change (which is, they say, characterised by elevated neuroticism and reduction in empathy, agreeableness and conscientiousness) is due to 'a neurogenic frontal lobe syndrome.' I think that the word which best sums up the character-changes is insouciance: a nonchalant lack of concern. Interestingly, the same authors comment that Alzheimer's disease can produce similar character changes.

I first encountered this strange mental state in a 32 year old woman with very severe MS. She was completely immobile and required constant nursing help. Her family had completely abandoned her; she never had visitors. Yet, at the same time, she seemed very content with life. Every morning I would ask her how she felt: she would invariably reply "I'm very well, thank you."

Not everyone with MS comes to have this syndrome; it seems only to occur prior to and during an actively progressive phase. It cannot be accounted for by primary autoimmune myelinopathy. I believe it likely to be a toxic state due to bacterial metabolites; there is some indirect evidence for this. Let's look at this more deeply.

Our cells live in a fairly rigorously controlled milieu, a world where homeostasis is important. Our cells are therefore very careful as to what they allow out into the extracellular fluid. Sometimes in disease this concern breaks down: in liver failure, volatiles are released into the general circulation (they can be smelled on the breath - the so-called fetor hepaticus.) When they reach the brain they cause symptoms of hepatic encephalopathy. This has an insidious onset, with cognitive impairment and a reversal of day/night sleep rhythms. Spatial awareness is compromised.

Unlike our cells, bacteria do not generally live in a homeostatic environment: they may even find an evolutionary advantage in pumping toxic compounds into their environment. The student of bacteriology quickly recognises the unique smell which many bacterial species or genera possess. These smells are due to volatile organic compounds.

Volatile toxins tend to affect the higher centres which form the personality first; think of alcohol and ether. Interestingly, a minority of people with MS personality change become disinhibited and take risks. As with intoxication with volatiles, personality changes in MS are accompanied by a profound elongation of reaction times.

Finally, there is the effect of antibiotics. Sarah had very aggressive disease, and had lost insight into it. On starting doxycycline she became delirious for some five days. Then she began to lose that MS personality change. I began to see something of her old self. It was like seeing someone leaving a prison cell.

I have to say that, in my experience, those who comply with treatment rapidly lose this strange mental state. Indeed, those who retain it are generally found, on close questioning, to have abandoned treatment. And that's the rub. Some people don't like losing the feeling of euphoria where their disabilities don't really matter and where the future is unimportant. The cold light of reality can be too much to bear. It is possible to conjecture that a state of habituation may occur, from which withdrawal may be painful. That is why a diligent and attentive carer is so important. The antibiotics must be seen to be swallowed.


Indeed, recent research shows that specific volatiles (tentatively hexanal and 5-methyl undecane) are found in the breath of persons with MS [Ionescu R et al. Detection of multiple sclerosis from exhaled breath using bilayers of polycyclic aromatic hydrocarbons and single-wall carbon nanotubes. ACS Chem Neurosci. 2011 Dec 21;2(12):687-93. Epub 2011 Sep 22.] Hexanal (hexanaldehyde) is a molecule associated with lipid peroxidation; it has a sweet 'springtime' odour, and is used as such by the fragrance industry. The human nose is very sensitive to hexanal, and can detect it in minute amounts (less than one part per billion). Now, I found that, while kissing, I could detect a very unusual sweet smell on Sarah's breath. It vanished with treatment.

Three Case Histories illustrate the nature of stereotypical psychological changes in persons with chronic C. pneumoniae brain infection.

1) A young woman in her early 20s came to see me. She had severe, very aggressive MS, almost certainly early Secondary Progressive disease. She was unable to walk, and entered the office in a wheelchair pushed by her fiancé. Despite the rapidly progressive nature of her illness, she was euphoric and lacked reason. On seeing me she laughed, and shouted: 'Here I come with my loyal retinue!' Behind her stood her mother and her fiancé, both looking exhausted and alarmed. She made a good but not complete recovery with antimicrobial treatment; she was able to return to part-time work.

2) I advised on a woman in her early 40s, a financier. She had bizarre mental symptomatology and was quite irrational. She had no insight into her illness. An MRI scan showed multiple white-matter hyperintensities typical of severe MS, though she had no motor or sensory signs or symptoms. She might be said to have had a forme fruste of MS. A C. pneumoniae specific IgA Elisa was morbidly raised (SeroCPquant: Savyon Diagnostics, Israel). Interestingly, she had a long history of Crohn's Disease for which she underwent a complete colectomy. She refused treatment and lost contact. Incidentally, a number of studies have linked Inflammatory Bowel Disease with white-matter hyperintensities in the brain. See [Chen M, Lee G et al. Cerebral white matter lesions in patients with Crohn's disease. J Neuroimaging. 2012 Jan;22(1):38-41.]

3) A girl of 12 presented with profound mental changes with hallucinations and short-term memory loss. She was failing at school. Her premorbid personality was one of high intelligence and thoughtfulness. Interestingly, a few months before the onset of symptoms her class had taken part in reaction-time testing. The class had been divided into pairs, the tester and the tested. The tester held a metre ruler by one end and released it; the pupil tested had to catch it. This girl's reaction time was the slowest in the class by a factor of ten. The girl also had a lupus-like rash on her face, involving her cheeks and the bridge of the nose. A C. pneumoniae specific IgA Elisa was morbidly raised (SeroCPquant: Savyon Diagnostics, Israel) as was the MIF. The girl was treated along the lines given on this site. She made a complete recovery with the return of her former intelligent and compassionate nature. She is now studying for a higher degree.

Page updated 10th January 2017

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