Some snippets of something I wrote ages ago, using excerpts from the Institute of Medicine study on tickborne disease:
The focus of this post will be Neuroborreliosis, which means when Lyme disease infects the CNS and brain.
I find it interesting to juxtapose the comments I see made by someone in discussion in one part of the report and then in the research portion of their report, information which at least partially contradicts what was stated.
Let me show you what I'm talking about here...
For example, page 9-12 has as part of the end of workshop discussion stating the following:
"A question was raised about who should comprise a clinical management team to treat patients with long-term symptoms. O’Connell noted that Lyme disease affects a number of different systems, depending to some degree on the borrelial genospecies causing the infection. Borrelia burgdorferi, which is the most common strain in the United States and also occurs in Europe, tends to cause Lyme disease arthritis. Borrelia garinii, which is strongly associated with neuroborreliosis, and Borrelia afzelii, mainly causing skin manifestations, are more common causes of Lyme borreliosis in Europe."
And when you read page A-180, Susan O'Connell has this to say:
"Although the differences between presentations of European and American Lyme neuroborreliosis have been stressed over the years, they may have been overemphasised in the case of early neuroborreliosis (Halperin, 2008). This is also supported by clinical experience in the UK, where between 10 and 20% of patients with serologically confirmed Lyme borreliosis acquired infections abroad, in mainland Europe or USA (HPA, 2011). Clinicians in the UK have noted marked similarities in acute neurological presentations of patients with USA-acquired infection and those acquired in the UK and other parts of Europe (Dillon, O'Connell and Wright (2010)."
I also found this to be interesting information on patients in Europe, on page A-178:
"Neuroborreliosis has been notifiable in Denmark since 1994; with an annual average of 83 cases (1.5/100,000), ranging from 41 in 2002 to 104 in 2006 (Christiansen and Mølbak, 2005) and 61 cases (1.1/100,000) in 2009 (EpiNorthData, 2011). Cases of disseminated and late borreliosis have been notifiable in Norway since 1995. Annual incidence of neuroborreliosis varied from 75 to 200 cases in the ten years 1995-2004 (average 3/100,000), with a marked increase of nearly 100 cases between 2003 and 2004 (Nygard et al., 2005). There were 273 notifications in 2009, a rate of 5.6 /100,000 (EpiNorthData, 2011). As neurological complications are the most significant manifestations of disseminated and late Lyme borreliosis in Europe data on neuroborreliosis obtained from the Slovenian, Danish and Norwegian notification schemes can give useful information on epidemiological trends in widely geographically separated areas of Europe."
So, in Denmark, neuroborreliosis is actually treated as a diagnosis which is medically notifiable separate from non-Neuroborreliosis Lyme disease - and in Norway, disseminated and late Borreliosis are also notifiable there.
If there is evidence patients are returning to Europe having been infected with Borrelia burgdorferi in US, and they develop neuroborreliosis and it's reportable in these countries, one would think they have a better epidemiological picture than the US does about neuroborreliosis as well as greater awareness.
You can't know how much something is a problem if you a) don't look for it and b) don't study it and c) don't make a record of it and let others know what's going on.
There's some circular reasoning at work here. The medical community has learned to look for certain signs as indicative of Lyme disease and not others; has been informed that neurological presentations occur in Europe and arthritic ones in the US - and that information is remembered and considered in diagnosis. But just because arthritis may be a common sign does not mean neurological ones cannot occur.
Making neuroborreliosis a reportable condition is a good idea because it makes the condition more visible, and encourages medical professionals to consider it in their diagnosis. Making it reportable may not lead to catching all cases - as it doesn't do so overall with Lyme disease - but it at least begins to address the problem of "we don't have 'x' in our state/province/country".
And I continue with these remarks:
If there is great concern about the significance of neuroborreliosis in Europe, why aren't all countries adopting the reporting schemes these countries are using?
So here's an interesting counterpoint...on page A-180, the following is stated:
"Less than 5% of European neuroborreliosis patients present with late neuroborreliosis with duration of symptoms from six months to several years (Mygland et al., 2010). This condition is likely to have a chronic course if left untreated and can affect the central and peripheral nervous system."
And prior to this, on page A-179, the following is stated:
"Neuroborreliosis accounts for between 10% and 20% of laboratory-confirmed cases each year and appears to be a useful sentinel for year-on year comparison. It has been estimated that there may be 2,000-3,000 cases of Lyme borreliosis annually in the UK (Health Protection Agency, 2011)."
So, to make a distinction here - if I'm reading this correctly - O'Connell is saying that 5% of all European neuroborreliosis patients present with late neuroborreliosis, but the overall percentage of cases of neuroborreliosis reported is 10-20% of all reported Lyme disease cases.
Also on that same page, it is stated:
"The EUCALB case definitions acknowledge similarities between the major manifestations of Lyme Borreliosis and North America, including erythema migrans, early neuroborreliosis and Lyme arthritis."
This is the piece that, between what I cited earlier and now concerns me: When Lyme disease is discussed in the US, many medical advice sites and articles written about Lyme disease seem to focus on it being a mild, flu-like illness where Lyme arthritis can develop if it's not treated early on.
And I think that may be how it is for a segment of the patient population who has an uncomplicated case, one involving a clear EM rash, and no coinfections, where one receives antibiotics soon after infection.
My concern is that the frequency of neuroborreliosis isn't something we're tracking that well in the US - and maybe it is being undiagnosed or misdiagnosed with other conditions.
The main reason tracking neuroborreliosis (and tying this into the subject of this thread, chronic Lyme disease) is so important becomes clear when you read the excerpts in the IOM report by Dr. Brian Fallon regarding neuroborreliosis and additional comments I made below:
CSF testing when I had early neurological symptoms is not something I was offered, either.
Which is ludicrous when early serological testing is especially prone to not detecting an infection. What should happen is if the person has a lot of neurological symptoms shortly after a tick bite, they should have a LP. And also the Western Blot. Repeated Western Blot testing which shows an increasing and changing serological profile would be useful in demonstrating antibody response.
It is also stated elsewhere in the summary report:
"An increment in immunoreactive bands is observed in the IgG immunoblots of sera of patients with neuroborreliosis and Lyme disease arthritis."
Saying that Borrelia burgdorferi doesn't cause neuroborreliosis isn't true. Saying it's rare isn't a helpful statement, and aside from utility, it's not even clear how rare it is because we simply lack that data. We don't know. What we have is a guess.
Referring to some studies (there are more studies on neuroborreliosis in the paper):
"Turning to the literature pertaining to patients with chronic persistent symptoms, Fallon noted a number of areas need additional research. A European study compared patients with neurologic Lyme disease to those with erythema migrans 3 years later and found that 50 percent of those with neuroborreliosis experienced persistent symptoms versus 16 percent of the EM patients (Vrethem et al., 2002). These results suggest that follow up studies on chronic symptoms, rather than focusing solely on early EM, should focus on the subpopulation of patients who present with neurologic or other disseminated symptoms."
"In a study of 60 U.S. patients with neuroborreliosis (16 with early and 44 with late neuroborreliosis), the sensitivity of PCR in CSF was 38% in early and 25% in late neuroborreliosis, and an inverse correlation was found between duration of antimicrobial treatment and PCR results (Nocton et al., 1996)."
So clearly, PCR isn't so great at detecting neuroborreliosis in early or late stage infection.
"With respect to pathophysiology, Borrelia act directly and can invade neural cells in vitro (Livengood and Gilmore, 2006); there are also indirect actions, such as the induction of local cytotoxins or inflammatory mediators (reviewed in Fallon et al., 2010). European studies show that pro-inflammatory cytokines are increased, and chemokines, excitotoxin, and quinolinic acid are increased in patients with neuroborreliosis (Weller et al., 1991; Halperin and Heyes, 1992; Widhe et al., 2004; Rupprecht et al., 2005)."
Diagnosing and properly treating early neuroborreliosis can prevent long term problems. It's clear that there's a correlation between developing neuroborreliosis and developing persisting symptoms, so anything that can be done to prevent it and treat it early would be beneficial. (It's not too heartening to read, however, that 16% of those with EM who did NOT receive a neuroborreliosis diagnosis also went on to develop persisting symptoms.)
Having objective evidence of early neuroborreliosis seems to be an issue. One can't rely on PCR, and if one doesn't have a rash but has other signs of infection and neurological symptoms, their case may be misdiagnosed as viral in nature. And even though Bell's palsy is said to be a sign of Lyme disease, it is also associated with viral infection and may be treated as such rather than more closely followed up on to determine it as being a case of Lyme disease. LP might help, but there's a possibility it won't detect infection - it's a matter of timing. Repeat serological testing could be useful, but how often is it actually used in the field?
What would be great is if someone could generate a measurable profile for the presence of neuroborreliosis using some sort of clear biomarker. Either the presence of specific proteins based on something similar to those found in the proteomics study that was done some time ago, which distinguished CFS/ME from those with post-treatment Lyme disease - or some other biomarker set.