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Poldark’s “Brain Fever” – Part 2

15/8/2018

 
***WARNING – SPOILERS***

​Previously …on Poldark’s “Brain Fever”…
Last week I looked at the curious case of Lieutenant Hugh Armitage who acquired a “Brain Fever” in a French prison before escaping with the help of Ross Poldark. Lt. Armitage then went on to seduce Poldark’s wife (that’s gratitude for you!) before eventually succumbing to “Brain Fever”, despite the excellent efforts of Dr Enys.
Poldarks brain fever dr enys
Dr Dwight Enys - the very picture of medical excellence!
​I worked through a differential diagnosis of the causes of headache and fever and went on to look at the infectious causes of chronic meningitis. This led us to the conclusion that Lt. Armitage died from granulomatous amoebic meningoencephalitis. This is often referred to as just GAE (granulomatous amoebic encephalitis) caused by Acanthamoeba spp., which whilst very rare is the only infective condition that I can identify that explained all of Lt. Armitage’s symptoms and signs.
 
So in this blog I am going to look at GAE in more detail, what it is, how it is diagnosed and how it is treated in the modern era.
 
What is granulomatous amoebic encephalitis?
GAE is a rare chronic infection of the central nervous system caused by Acanthamoeba spp. There are apparently only about 150 cases documented in the literature.
 
In most cases there is some form of underlying condition that predisposes to infection e.g. diabetes mellitus, alcoholism, cirrhosis, HIV infection, chronic renal failure, cancer or chemotherapy as well as bone marrow transplantation. It can occur in immunocompetent people as well. This is the only part of the Poldark story that doesn’t completely fit, because as far as we know Lt. Armitage wasn’t immunosuppressed, but as it can occur in immunocompetent patients… I’m sticking to my diagnosis… it’s my blog!
 
Acanthamoeba spp. are found in the environment in soil and water, especially brackish water, sewerage, humidifiers, heating systems and contact lens fluids. They are ubiquitous, being found on all continents except Antarctica. The exact route by which the parasite is acquired isn’t certain. The most likely is through inhalation as Acanthamoeba spp. can be found in the nasal mucosa of apparently healthy people as well as those who are unwell. Another possible route is through the skin. Whatever the route of entry, infection occurs by haematogenous spread to other parts of the body, especially the brain. Person-to-person transmission does not occur.
 
How does GAE present?
The incubation period for GAE is unknown, but is thought to be up to 1-2 weeks. Patients typically present with a prolonged history, over weeks to months, of worsening headache, low-grade fever, visual disturbance, changes in behaviour and sometimes neurological deficits. As the infection worsens the patient experiences raised intracranial pressure, worsening of the headaches and extension of the neurological symptoms and signs. Eventually the patient becomes drowsy, lapses into a coma and dies.
 
If the patient undergoes a lumbar puncture, before the raised intracranial pressure makes this too dangerous, the CSF shows a slightly raised white blood cell count with predominantly lymphocytes. The protein is high and the glucose is normally low. It isn’t usually possible to see the parasite in the CSF.
 
How is GAE diagnosed?
Radiology using CT or MRI scans will show single or multiple ring-enhancing lesions, usually in the parietal and temporal lobes. Ring-enhancement refers to the collection of a specific contrast media, used in the scan, surrounding an area of abnormality. This usually suggests an area of inflammation surrounding the abnormal brain tissue.
 
There is only one sure fire way to diagnose GAE and that is with a brain biopsy. Histopathological examination of brain tissue will see the trophozoites and cysts of Acanthamoeba spp. and confirms the diagnosis. It isn’t usually necessary to use special stains as the parasites can be stained using the normal haematoxylin-eosin stain, however immunofluorescent stains are apparently available which make them easier to find. Nowadays in the developed world we would tend to use PCR to identify the parasite in brain tissue.
 
How is GAE treated?
Because GAE is rare there isn’t yet a standard treatment regimen. Most regimens use combinations of drugs; one such combination is Miltefosine, Fluconazole and Pentamidine isethionate. Other drugs which have activity against Acanthamoeba spp. in vitro include Co-trimoxazole, Metronidazole, Azithromycin, Clarithromycin, Rifampicin, Flucytosine and Caspofungin.
 
If there is only a single lesion in the brain then this should be surgically resected if possible.
 
The mortality from GAE even with treatment is approximately 90%.
 
So it looks like poor Lt. Armitage was doomed from the moment he acquired his Acanthamoeba spp. Even if Dr Enys had suspected the diagnosis, had had access to a modern diagnostic laboratory and all of the expensive antimicrobials available to treat this serious infection, it is unlikely that Dr Enys could have saved our patient’s life. In the end it was probably for the best, at least Demelza’s affair ended and her and Ross got back together, although Jeffery Charles’ comment that Valentine looked like Uncle Ross followed by Elizabeth’s death means it has all become a little bit too much of a soap opera for me recently… bring back the gritty 19th Century social drama and the next medical conundrum. Did I hear Dr Enys say, “The children had ague”, I think I’ve covered that before, oh bother… I’ll have to wait for the next series and see what historical infection raises its head next…

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    Blog Author:

    David Garner
    Consultant Microbiologist
    Surrey, UK

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