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Neurological Complications of Lyme Disease

Posted: Tue 4 Nov 2014 11:16
by RitaA
Although this article was written (or at least published) in 2008, the definitions probably haven't changed much (if at all) since then. Some of the information may well be out of date in light of more recent research and published articles (including case reports), but I still think it's worth posting here for historical purposes and because it's written by two doctors whose names aren't typically associated with Lyme disease.
Neurological Complications of Lyme Disease

VOLUME 91 NO.7 JULY 2008

Syed Rizvi, MD, and Amanda Diamond, MD

A tick-bite associated rash with later neurological manifestations, including paralysis and meningitis, had been documented in Europe for several years before Lyme arthritis was recognized in the 1970s.1-4 The illness was later understood to be part of a multisystem disease caused by spirochetae and transmitted by Ixodes ticks. 5,6 Borrelia burgdorferi, although initially thought to be a single species, has been found to have several sub-species. These subgroups may be responsible for the variation in clinical symptoms observed in different parts of the world.7

The pathophysiology of neuroborreliosis is difficult to demonstrate, but mimics other spirochetal infections. Infection is local with subsequent dissemination. During this time spirochete numbers are high. B. burgdorferi components that induce cytokine production by T and B cells produce immune activation and indirect cell damage. Central nervous system involvement is common and clinical syndromes tend to occur in stages.7

Lyme disease has been implicated in a variety of peripheral and central nervous system disorders. The neurological syndromes are often accompanied by more general complaints (arthralgias, fatigue, myalgias). Earlier neurological symptoms, or those occurring during dissemination within weeks to months, tend to be more clinically obvious and develop in an estimated 15% to 20% of patients.4 Several late syndromes seem to follow a more insidious course.8 For purposes of simplification, disorders of the peripheral and central nervous systems will be reviewed separately.


The most common peripheral manifestations of Lyme disease are cranial neuropathies, peripheral neuropathies and radicultis. However, many other syndromes, including a "Guillian Barre-like" syndrome, motor neuron disease, axonopathies, brachial and lumbar plexopathies, mononeuropathy multiplex and even myositis have been described. 7

Radiculoneuropathy. Painful radiculitis is one of the most common early neurologic symptoms of Lyme disease in Europe. Incidentally, it was also part of the symptom-complex described in the first patient reported with the syndrome.1 Usually occurring within the first weeks to months in the infection, the radiculoneuropathies of Lyme disease have included motor, sensory and mixed symptoms. They are usually self-limited and may be easily mistaken for nerve-impingement syndromes, with segmental symptoms of weakness, sensory or reflex changes.9 The symptoms may not occur in the region of the tick bite. Electrodiagnostic testing usually shows multifocal mild sensorimotor involvement. 10, 11

Cranial neuropathies. Involvement of cranial nerves, particularly the seventh nerve, may be present in up to 50%-75% of all patients experiencing neurologic syrnptoms.4 Multiple cranial nerves may be involved simultaneously.9 Reports include symptoms of every cranial nerve except the olfactory nerve. The facial nerve involvement is reported to be bilateral in up to one third of cases. II Facial nerve symptoms may not affect taste or hearing, indicating that involvement may be outside the subarachnoid space. Additionally, CSF analysis in isolated Lyme disease facial palsy may be normal. Complete recovery occurs in 80-90% of patients within weeks to months.

"Guillain Barre-like" syndrome. Although rare, an acute and severe syndrome of diffuse polyneuropathy, including bifacial weakness, may mimic the symptoms of Guillan Barre. A CSF lymphocytic pleocytosis and/or neurophysiologic testing may help differentiate between the syndromes.7

Peripheral neuropathy. Symptoms of peripheral neuropathies in patients with Lyme disease tend to be primarily sensory, occurring in a stocking-glove fashion, although patchy paresthesias may also be noted. In some European patients, a dermatologic manifestation is often associated with the neuropathy. Labeled acrodermatitis atrophicans, the skin becomes tissue-thin and discolored.

The same patients have been discovered to develop an axonal neuropathy* in the affected limb.9. In the case of chronic infection, it has been estimated that one in four patients may have peripheral nerve involvement. These patients may present with mainly sensory symptoms. 10,11


Meningitis. Although many syndromes involving the central nervous system remain controversial, several have been well-defined. Certainly, the early appearance of lymphocytic meningitis is well recognized. Mildly increased CSF pressure with headache and papiledema may occur. The lymphocytic pleocytosis usually includes tens to hundreds of lymphocytic cells per mL. A mild elevation of protein may also be seen, with CSF glucose usually remaining within a normal range to minimally decreased. 12 The 'typical' symptoms that usually occur with 'aseptic' meningitis, such as photophobia, headache and neck stiffness, are extremely variable with Lyme meningitis. 11,12

Intracranial hypertension syndrome. A rare complication of Lyme disease resulting in headache and potential papilledema, this syndrome seems to be associated more often with children and adolescents. CSF abnormalities may occur. There does not appear to be a correlation with female sex or obesity, as with pseudotumor cerebri. 11,13

Encephalomyelitis. A chronic manifestation of Lyme disease, encephalitis is rare in North American (nearly all cases have been reported in Europe). On MRI there is evidence of parenchymal involvement. This can include hemispheric or brainstem abnormalities and is usually nonspecific, although may mimic ischemic patterns. 11

Myelopathy. Patients may present with symptoms of transverse myelitis so that Lyme disease should be considered in the diagnosis of these patients. 11, 14 Rarely, a transverse myelopathy may accompany Lyme radiculoneuritis. This typically occurs at the same level as radicular involvement and may be preceded by a leptomeningitis.12

Lyme encephalopathy. This may be the most common late neurologic manifestation of Lyme disease. Patients express difficulties with concentration, sleep disturbance, emotional lability, memory and attention. 11,15,16 Despite studies including requirements for CSF abnormalities and SPECT imaging, the definitive diagnosis of Lyme encephalopathy remains elusive. 16 In the consideration of acute encephalopathy, one should note that persons with Lyme-induced cognitive changes likely have a mild encephalitis; these patients should not be confused with mental status changes associated with systemic symptoms. 17 Such patients are likely to have objective findings on neuropsychiatric testing and such a diagnosis should only be made in the presence of appropriate findings after testing has been performed by a qualified professional. This is distinct from the more subjective symptoms patients often experience for weeks to months following an episode of acute infection with B. burgdorferi (discussed below).



The crucial element for the consideration of neurologic Lyme disease is the presence of an indicative neurologic symptom. Laboratory data should be complimentary and supportive of clinical findings. In evaluating response to therapy, the clinician must remember that many neurologic illnesses improve with time, regardless of treatment. 17 Unfortunately, sensitivity of culture in nervous system infections is low (only about 10% in CSF in Lyme meningitis). The sensitivity of PCR testing appears to be low as well. Confirmation of the diagnosis, therefore, relies largely on serologic testing. Spinal fluid can, however, be tested for the presence of anti-B. burgdorferi antibodies. 19


Researchers have also described a B-cell-tropic chemokine, CXCLl3, which appears abnormally elevated in CSF of patients with Lyme neuroborreliosis. If confirmed, this cytokine might serve as a marker to assist in the confirmation of the diagnosis of neuroborreliosis.23


Although the general recommendation in the US is to use parenteral antibiotics whenever the nervous system is involved, there is considerable evidence in the European literature suggesting oral doxycycline (200-400mg/day) may be equally effective in most patients. At the recommended doses it appears that the CSF concentrations of doxycycline exceed minimum inhibitory concentration for most strains. Although there are strain differences between United States and Europe, there probably is not a significant difference in antimicrobial susceptibility. 24


Syed Rizvi, MD, is Director, Rhode Island Hospital Multiple Sclerosis Center, and Assistant Professor of Clinical Neurosciences, Warren Alpert Medical School of Brown University.

Amanda Diamond, MD, is a Neurology Fellow, Warren Alpert Medical School of Brown University.

Re: Neurological Complications of Lyme Disease

Posted: Tue 4 Nov 2014 12:57
by duncan
Thank you for posting this, RitaA.

I also do not recognize these authors' names, but it appears they are from Brown. Don't know how far that Ivy connection goes, but I tried to read this on the basis of its own merits. Still, I couldn't shake the feeling that I'd read this before.

Although a research paper, I think this is written with clinicians in mind. This is especially true with diagnoses as the authors declare almost immediately that the crucial element in any diagnosis of NB is the presence of neurologic symptoms. They declare that laboratory data should be only complimentary and supportive of clinical findings . (The reality is it can be difficult - if not impossible - to get insurance to pay for treatment for NB in the absence of laboratory data. So, suggesting that lab support is complimentary only to a clinical diagnosis seems to me a bit removed from the real world, or at least, the Lyme treatment world, i.e. post-diagnosis, when you petition for treatments that have to be paid for).

I found particularly reassuring the observation that "many neurologic illnesses improve with time, regardless of treatment." I'm not sure why they decided to add that claim. I am sure it is true for some diseases of the brain and CNS, maybe even some NB cases. Perhaps it seems calming and mitigates concern that NB might be serious or long lasting.

Then they point out that sensitivity in CSF testing is low, and that with the possible exception of looking for the presence of antibodies in the CSF, it's better to try to obtain confirmation from serology. And then they mention CXCL13, as if it currently enjoys widespread acceptance and can be used as a reliable marker (it can't yet as far as I am aware).

Treatment is even better than many of us NB sufferers thought. Not only is it possible that we will not need IV therapy, it seems oral doxy may be sufficient after all. Better still, our neurologic disease may improve on its own.

Ok, then. :D

I am not sure what or whose reality this study addresses, but I know it isn't mine. Maybe some neurologic illnesses do improve with time irrespective of treatment, but mine hasn't and neither has anybody that I know or read about who has had NB. Getting treated for NB is next to impossible without confirmatory labs where I live (in the US), and some insurance companies insist on positive MRI's backed with proof of antibody presence in CSF. These would be some of the same sort of supportive tests that these authors refer to as having low sensitivity because, you know, it's CSF. Worse, in many countries - and in some places in the US - an NB patient must also sport a positive antibody index. The antibody index I find particularly onerous because I have not been able to authenticate its voracity in cases of late stage NB with Bb sensu strictu. (I'm not even convinced of its merits with sensu latu, but that's a different thread.)

And treatment...What can I say?

It's nice to read of a Lyme diagnostic and treatment world that is so very different than the one I struggle with.

Re: Neurological Complications of Lyme Disease

Posted: Tue 4 Nov 2014 16:59
by RitaA
Yes, the article is most definitely written by medical professionals as opposed to patients who are still struggling with health issues after treatment for Lyme disease. The references the authors used are those that many of us have become quite familiar with, so the content probably shouldn't surprise us all that much.

There are indeed patients -- and especially those infected in Europe -- who actually do benefit from 200 mg of doxycycline twice a day (i.e. a total of 400 mg per day). The worst of my neurological problems (including stroke-like symptoms more than likely caused by B. garinii given my travel history to Finland) did in fact begin to resolve after 3 months of oral antibiotics, however it took much, much longer for me to believe that I was actually on the road to recovery. Based on what I've read and heard during the past 3 years, recovery can also be incomplete even after a year (or more) of IV antibiotic treatment -- and especially for those with a much-delayed diagnosis and treatment. In other words, a full recovery isn't guaranteed for anyone with late Lyme disease regardless of the treatment they receive.

With any luck, some of the antibiotics currently being viewed as potentially more effective against "persister cells" will change the course of Lyme disease history. That said, I strongly suspect it will take many more years before clinical trials using those antibiotics are even designed, and that's obviously not going to be soon enough for countless people who are suffering right now.

In my case -- and only because of blood clotting issues I was experiencing at the time -- IV antibiotic treatment (which my Infectious Diseases specialist would have otherwise prescribed) was not considered safe. It had nothing to do with insurance in my particular case because Ontario's provincial health plan would have covered all of the associated costs had the treatment been ordered by an ID specialist. I consider myself fortunate that oral antibiotics took me as far as they did despite my still-incomplete recovery.

Although I'm not a mind reader, I'm guessing the authors were referring to conditions like viral meningitis that may in fact resolve without any treatment. Migraines also tend to decrease in frequency and severity after menopause in some women (although for a minority, things actually get worse). I'm not familiar with any other examples of neurological conditions getting better with time (but no treatment) off the top of my head, but that's likely because I didn't attend medical school.

One thing I did forget to mention in my original post is that things haven't really changed much (if at all) for Lyme disease patients since 2008. Make that the 1970's when it comes to treatment options and so much more.

Re: Neurological Complications of Lyme Disease

Posted: Tue 4 Nov 2014 18:44
by ChronicLyme19
duncan wrote:Thank you for posting this, RitaA.
Yes, very.
I found particularly reassuring the observation that "many neurologic illnesses improve with time, regardless of treatment." I'm not sure why they decided to add that claim. I am sure it is true for some diseases of the brain and CNS, maybe even some NB cases. Perhaps it seems calming and mitigates concern that NB might be serious or long lasting.
Maybe not many, but some do. I'll add my anecdote here that my coworker just had bell's' palsy and right arm numbness that resolved on it's own.

So RitaA, all your posts on cranial nerve involvement left me wondering about them. So I went to look them up and stumbled across this: ... .php?id=13

That's THE exact region that is all screwed up in my back, and no place else. This may be the explanation I was looking for as to why my T2-T3 vertebrae don't stay in place and why I have problems with just that region, especially my traps.

Also, the XI cranial nerve involvement would help explain the "Lyme shrug".

Re: Neurological Complications of Lyme Disease

Posted: Tue 4 Nov 2014 23:06
by RitaA
Wow, ChronicLyme19, that's an amazing find!

It's very satisfying to put even a few clues/pieces of our unique medical puzzle together -- something it seems many of us are left to do on our own given how dismissive some medical professionals can be (and often are) when they are out of their comfort zone.

Re: Neurological Complications of Lyme Disease

Posted: Wed 5 Nov 2014 1:23
by ChronicLyme19
From the descriptions I've read so far I'm hoping this is the answer to my back issues. If it is, that will make 2 neurologists, and three orthopedics that have failed to explain it. Given that I have late stage lyme and other peripheral neuropathies, and have had severe mood disturbances, memory problems and vision problems I would not be surprised if this was the cause. I already know it's been in my brain. The pressure in the back of my head near where your head meets the neck was my very first symptom.

Re: Neurological Complications of Lyme Disease

Posted: Wed 5 Nov 2014 4:00
by jjs
ChronicLyme19 wrote:From the descriptions I've read so far I'm hoping this is the answer to my back issues. If it is, that will make 2 neurologists, and three orthopedics that have failed to explain it. Given that I have late stage lyme and other peripheral neuropathies, and have had severe mood disturbances, memory problems and vision problems I would not be surprised if this was the cause. I already know it's been in my brain. The pressure in the back of my head near where your head meets the neck was my very first symptom.
I also have a burning pain that comes and goes in my back. It's a burning sensation that covers the area shown in the graphic from your link. It mostly affects my right side although, it does occasionally switch over to the left. From what I have been able to tell this is a symptom of radiculoneuropathy sometimes also referred to as radicular pain. I am not positive on this as most the information I've run across, as it pertains to Lyme Disease offer only a vague description of symptoms. It is also found more often in people infected in Europe and Asia as opposed to the arthritis that is more often seen in U.S. infections.

As for the assertion made in the paper about most neurological illnesses improving over time regardless of treatment, that seems like pretty dangerous advice to be throwing around. Yes, there are some illnesses that can be said of, but there are just as many if not more that can be fatal without intervention. Unfortunately there are way more incentives for a doctor to take the wait and see approach even when it is not in the patients best interest. I was not surprised at all when I heard about the Dallas doctor who prescribed antibiotics for Ebola and sent the patient on his way. This doctor jeopardized his community and most likely cost the patient his life but I doubt any disciplinary steps will be taken so this type of behavior will continue.

Re: Neurological Complications of Lyme Disease

Posted: Tue 11 Nov 2014 0:59
by ChronicLyme19
Hmmm, seems cranial nerve XI involvement is possible. Found one documented case, but can't view the article.

Eur Neurol. 1982;21(5):340-2.
Multifocal neuropathy and vocal cord paralysis in relapsing fever.
Olchovsky D, Pines A, Sadeh M, Kaplinsky N, Frankl O.

A 19-year-old soldier developed multifocal neuropathy following an infection with tick-borne Borrelia. He suffered from involvement of the right accessory nerve, the right brachial plexus and the left recurrent laryngeal nerve. As was expected, all these complications were reversible. In contrast to louse-borne relapsing fever, neurological manifestations in the tick-borne variants are not common. To the best of our knowledge, vocal cord paralysis has never been described before. ... l+nerve+XI

Asked the LLMD today and he said he'd have to look it up.

Re: Neurological Complications of Lyme Disease

Posted: Thu 20 Nov 2014 21:31
by phyfe
CL19, Has he told you anything yet? Just curious. :)

Re: Neurological Complications of Lyme Disease

Posted: Mon 24 Nov 2014 3:48
by ChronicLyme19
Hi Phyfe, no not yet. Tho I did look up his question, that yes you can have motor nerve involvement without a pain syndrome in the traps, which is mainly what I have. The nerves that control the feeling in the traps for are through other nerves in your neck at C3 and C4. For me I do get pain with it, but that happens only when my left traps pull my spine out of place and then it pinches the nerves near T2-T3. For some reason my right traps aren't responding to physical therapy and so all PT does is make my left traps super tight until it pulls my spine and ribs out and they get stuck.

I'm headed to a local neurologist next week to try and figure out how exactly it's affecting that nerve, whether it's in the brain part or the part of the accessory nerve that escapes the skull into your neck. It's obviously not completely damaged for me, but my guess is partial damage or maybe the inflammation from my brain is pressing on the nerve causing it to not work right. The problem is how to prove that since the chiropractor said that won't show on the MRI. The chiro agreed that sounded like a very plausible reason why I still have trap issues despite almost a year of chiropractic care and PT and no progress in months.

I guess the question is, when Lyme affects the other cranial nerves, like the 7th cranial nerve, how do they confirm it's that? Or do they just go by the symptoms alone?

I know there is still crap living in my brain around the region of those nerves. They put me on rifampin two weeks ago and I had a huge herx. My vision started going blurry, I was super nauseous (the brain kind not the stomach kind) and had chills, but no fever. It felt some pretty intense headache/pressure on the back of my skull where my head and brain steam meet, which was my first symptom when I got bitten 3.5 years ago. I also got kinda giddy from it which sure beats the panic attack version of herxing.

If the local neuro can't figure it out, then I'll be headed into the city for a second opinion. For now at least the herx has subsided some. The not so great thing is that if I am right, that it means IV time. :(

I'll keep you posted.