Updated July 2015
(Also check out our section on psychiatric Lyme)
Inflammation in the pathogenesis of lyme neuroborreliosis.
Am J Pathol. 2015 May;185(5):1344-60. doi: 10.1016/j.ajpath.2015.01.024. Epub 2015 Apr 16.
Ramesh et al
Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi, affects both peripheral and central nervous systems. We assessed a causal role for inflammation in Lyme neuroborreliosis pathogenesis by evaluating the induced inflammatory changes in the central nervous system, spinal nerves, and dorsal root ganglia (DRG) of rhesus macaques that were inoculated intrathecally with live B. burgdorferi and either treated with dexamethasone or meloxicam (anti-inflammatory drugs) or left untreated. ELISA of cerebrospinal fluid showed significantly elevated levels of IL-6, IL-8, chemokine ligand 2, and CXCL13 and pleocytosis in all infected animals, except dexamethasone-treated animals.
Cerebrospinal fluid and central nervous system tissues of infected animals were culture positive for B. burgdorferi regardless of treatment. B. burgdorferi antigen was detected in the DRG and dorsal roots by immunofluorescence staining and confocal microscopy.
Histopathology revealed leptomeningitis, vasculitis, and focal inflammation in the central nervous system; necrotizing focal myelitis in the cervical spinal cord; radiculitis; neuritis and demyelination in the spinal roots; and inflammation with neurodegeneration in the DRG that was concomitant with significant neuronal and satellite glial cell apoptosis. These changes were absent in the dexamethasone-treated animals.
Electromyography revealed persistent abnormalities in F-wave chronodispersion in nerve roots of a few infected animals; which were absent in dexamethasone-treated animals. These results suggest that inflammation has a causal role in the pathogenesis of acute Lyme neuroborreliosis.
Teenager with stroke symptoms actually had Lyme disease
March 2, 2015
A Swiss teenager, recently returned home from a discotheque, came to the emergency department with classic sudden symptoms of stroke, only to be diagnosed with Lyme disease. The highly unusual case presentation was published online last Thursday in Annals of Emergency Medicine – see below (“Acute Lyme Neuroborreliosis with Transient Hemiparesis and Aphasia”).
“Everything about her symptoms indicated stroke: speech deficits, poor comprehension and right-sided face and arm weakness, so we considered treating her with clot-busting drugs” said lead study author Arseny Sokolov, MD, of the Department of Clinical Neuroscience, Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland. “But a 16 year-old having a stroke, while not unheard of, would be quite rare so we looked at other possibilities and found Lyme.”
Brain imaging was not suggestive of stroke either, but revealed circumscribed brain dysfunction. The treatment team performed a spinal tap. The patient’s spinal fluid showed elevated white blood cell counts and Lyme neuroborreliosis was diagnosed, so the treatment team began a course of antibacterial and antiviral agents. The patient improved immediately after treatment began.
“The imaging findings for the first time demonstrate acute brain dysfunction that appears to be directly related to neuroborreliosis” said senior co-author Renaud Du Pasquier, MD, neurology chairman at the Centre Hospitalier Universitaire Vaudois in Lausanne. “It may point out future perspectives for research on the underlying mechanisms.”
Lyme disease is caused by Borrelia burgdorferi bacteria, and is known as “the great imitator,” as its symptoms can mimic so many other diseases. Many patients have Lyme for a long time before a proper diagnosis is rendered. When that happens, serious long-term complications are the result.
“The uncommon set of symptoms our patient had show why Lyme is a ‘chameleon disease’ of the emergency department,” said Dr. Sokolov. “Furthermore, the patient had no history of tick bite. This curious case just shows the careful detective work that is involved in such a large portion of emergency medicine.”
Acute Lyme Neuroborreliosis With Transient Hemiparesis and Aphasia
Sokolov, Arseny A. et al.
Annals of Emergency Medicine , Volume 66 , Issue 1 , 60 – 64
Published Online: February 25, 2015
Nervous system involvement in Lyme disease often mimics other conditions and thus represents a diagnostic challenge, especially in an emergency department setting. We report a case of a female teenager presenting with sudden-onset aphasia and transient right-sided faciobrachial hemiplegia, along with headache and agitation. Ischemia, vasculitis, or another structural lesion was excluded by brain imaging. Toxicologic evaluation results were negative. Cerebral perfusion computed tomography and electroencephalography showed left parietotemporal brain dysfunction. Lumbar puncture result, although atypical, suggested bacterial infection and intravenous ceftriaxone was initiated. Finally, microbiological cerebrospinal fluid analysis revealed Lyme neuroborreliosis, showing specific intrathecal antibody production and high level of C-X-C motif chemokine 13. The patient rapidly recovered.
To our knowledge, this report for the first time illustrates that acute-onset language and motor symptoms may be directly related to Lyme neuroborreliosis. Neuroborreliosis may mimic other acute neurologic events such as stroke and should be taken into diagnostic consideration even in the absence of classic symptoms and evolution.
Lyme disease –induced polyradiculopathy mimicking amyotrophic lateral sclerosis
November 2014, Vol. 124, No. 11 , Pages 859-862 (doi:10.3109/00207454.2013.879582)
Ahmet Z. Burakgazi:Neuroscience Section, Department of Medicine, Virginia Tech Carilion School of Medicine, USA
Importance: To describe a case of predominantly motor polyradiculopathy secondary to Lyme disease that can mimic motor neuron disease and has been rarely reported.
Observations: A 64-year-old man presented with a 1-month history of rapidly progressive weakness involving bulbar, upper limb and lower limb muscles. The physical examination showed widespread weakness, atrophy, fasciculation, and brisk reflexes. The initial electrodiagnostic test showed widespread active and chronic denervation findings. The initial physical and electrodiagnostic findings were suggestive of Amyotrophic Lateral Sclerosis (ALS). However, blood serology indicated possible Lyme disease. Thus, the patient was treated with doxycycline. The clinical and electrodiagnostic findings were resolved with the treatment.
Conclusion and Relevance: The diagnosis of Lyme disease can be very challenging and it can mimic other neurological disorders such as ALS or Guillain-Barre syndrome (GBS). Careful and detailed examination and investigation are required to confirm the diagnosis and to prevent misleading inaccurate diagnoses.
Acute polyradiculoneuritis syndrome: clinical observations and differential diagnosis [important to rule out Lyme disease].
Authors: Supanc V, Stojić I, Vargek-Solter V, Breitenfeld T,
Roje-Bedeković M and Demarin V Citation: Acta Clin Croat 2012(Jun); 51(2): 195-9.
Clinically, patients with neuroborreliosis manifested flaccid tetraparesis, peripheral facial nerve paresis, bulbar paresis, ocular motility disorders, and sensory symptoms of radicular pain and paresthesias. Considering the relatively high prevalence of neuroborreliosis in north-west Croatia, it is important to exclude meningoradiculoneuritis caused by Borrelia burgdorferi on differential diagnosis of GBS in these patients.
SPECT Brain Imaging in Chronic Lyme Disease
Clinical Nuclear Medicine: September 2012 – Volume 37 – Issue 9 – p e219–e222
Donta et al
From the *Department of Medicine (Infectious Diseases), Boston University Medical Center, Boston, MA; †Department of Diagnostic Imaging (Nuclear Medicine), Rhode Island Hospital, and The Warren Alpert Medical School of Brown University, Providence, RI; and ‡Department of Diagnostic Imaging and Therapeutics (Nuclear Medicine), University of Connecticut School of Medicine, Farmington, CT.
Dr Donta is currently with the Department of Medicine (Infectious Diseases), Falmouth Hospital, Falmouth, Mass.
Objectives: Lyme disease is an infectious disease that frequently involves the central nervous system, leading to cognitive and/or mood dysfunction. The basis for these symptoms remains to be defined but may be the result of a vasculitis or metabolic abnormality secondary to the infection. SPECT scans of the brain might provide an objective measure of abnormalities present in patients with otherwise difficult to objectify clinical findings. The objective of this study was to determine the frequency, location, and severity of abnormalities in SPECT scans of the brain of patients with chronic Lyme disease.
Methods: A total of 183 individuals who met the clinical definition of chronic Lyme disease underwent SPECT scanning of the brain using 99mTc and standard nuclear imagine techniques. Abnormalities of perfusion to affected areas of the brain were defined as mild, moderate, or severe.
Results: Of all patients, 75% demonstrated abnormalities in perfusion to various areas of the brain, most notably the frontal, temporal, and parietal lobes. Patients considered to be seropositive and those considered seronegative had similar rates, types, and severity of perfusion defects. Abnormalities of MRI of the brain were seen in 14% of patients. Treatment with antibiotics, especially those with intracellular-penetrating activity, resulted in resolution or improvement of abnormalities in 70% of patients over a 1- to 2-year period.
Conclusions: Brain SPECT scans are abnormal in most patients with chronic Lyme disease, and these scans can be used to provide objective evidence in support of the clinical diagnosis. The use of certain antibiotic regimens seems to provide improvement in both clinical status and SPECT scans. (see full paper below)
Cerebral vasculitis and stroke in Lyme neuroborreliosis. Two case reports and review of current knowledge.
Cerebrovasc Dis. 2008;26(5):455-61. doi: 10.1159/000155982. Epub 2008 Sep 23.
Topakian R, Stieglbauer K, Nussbaumer K, Aichner FT.
We report on 2 patients with cerebral vasculitis and stroke due to Lyme neuroborreliosis (LNB). Both patients had a prodromal stage involving headaches, and showed meningeal enhancement in addition to ischemic infarctions on brain magnetic resonance imaging and diffuse vasculitis on vascular imaging. Serological and cerebrospinal (CSF) fluid studies confirmed the diagnosis of active LNB. Ceftriaxone for 3 weeks led to an excellent recovery and improvements in the CSF examination findings. Stroke physicians should be aware of this rare presentation of LNB. A review of the current knowledge on cerebral vasculitis due to LNB is provided.
2008 S. Karger AG, Basel.
[Guillain-Barré syndrome in a course of early cutaneous type of Lyme borreliosis: diagnostic and therapeutic difficulties].
Neurol Neurochir Pol. 2005 Sep-Oct;39(5):412-6.
Wiszniewska M1, Szmaglińska H, Kozubski W.
A case is reported of a 33-year-old man in whom Guillain-Barré syndrome (GBs) developed three weeks after a tick’s sting. At the sting site typical for an early cutaneous type of Lyme borreliosis — erythema migrans — appeared. The demyelinating polyradiculoneuropathy of GBs occurred after disappearance of erythema migrans, and was manifested by progressive neuropathic symmetrical limb weakness with distal numbness and pain, and bilateral facial paralysis.
The GBs was confirmed by electrophysiological examination and elevated protein concentration with a normal range of cells in the cerebrospinal fluid. Antibodies IgM and IgG against Borrelia burgdorferi in the blood serum and cerebrospinal fluid assessed using immunoenzymatic assay, MEIA, were negative on account of their early search.
The above findings suggested that the GBs appearance after the probable Borrelia burgdorferi infection was in fact due to that infection. The patient recovered after treatment with plasma-phoresis and corticosteroid therapy followed by intravenous immunoglobulin, and physiotherapy. This is the first case in the Polish neurological literature of GBs with an early skin form of borreliosis which developed after the tick’s sting.
The Neuropsychiatric Manifestations of Lyme Borreliosis
Psychiatric Quarterly, Vol63, No 1,Spring 1992
Lyme borreliosis (Lyme disease), a tick-borne spirochetal illness, has multi-systemic involvement and is rapidly increasing in certain areas of the United States. A lthough its neurologic manifestations are becoming increasingly well recognized, its psychiatric presentations are not well known. The first section of this paper will provide an overview of Lyme borreliosis and a review of the relevant neuropsychiatric literature. The second section will provide clinical descriptions of some common neuropsychiatric symptoms as well as a discussion of the problems typically faced by patients with this illness. Guidelines to assist the clinician in working with these patients will be presented.
Neurological Symptoms caused by Lyme Disease
This page covers some of the symptoms plus a short video by Dr Daniel Cameron on psychiatric Lyme, chronic Lyme (inc studies & trials) plus costs of treating serious infections..
Dr Cameron’s website can be found at: http://danielcameronmd.com/
LYME IS A BRAIN DISEASE (neuroborreliosis)
By Virginia T. Sherr 7-31-05
Lyme borreliosis is a brain disease as well as a multisystemic disease caused by spirochetal bacteria.* Quite frankly, it is an infection that has been burdened with a thousand inaccurate medical diagnoses. The manner in which the current pandemic of tertiary Lyme disease, neuroborreliosis, has usually been handled— either angrily dismissed or strangely misdiagnosed–throughout the 30 years following its “discovery,” has blemished the historic excellence of modern American Medicine.
After all the years, neuroborreliosis is still actually considered rare by a majority of physicians, most of whom are spirochetally naïve. Officially tallied patients (the numbers showing a dip down to 19,804 cases in 2004 after flawed reporting styles were instituted), when combined with uncounted cases may approach upward of an annual quarter million new borreliosis infections in the USA alone. And Lyme infections have been verified as present on all but one continent, globally. The disease is more often than not accompanied by several of a half-dozen or so of the other serious tick-borne co-infections that currently have been identified.
Losses of acuity in the human brain’s visual cortex have been observed as early as 6 hours following the toxic bite of an infected tick. Lyme may persist after too brief a period of treatment or if there has been no treatment, and may result in chronic infections whereupon Lyme borreliosis becomes a potential cause of every symptom in medical and psychiatric lexicons. It is the “Great Imitator” of this Millennium, spirochetal paresis (neuro-syphilis) having been its precursor and its model.
Chronic or persistent Lyme disease–neuroborreliosis–seldom is identified by the symptoms of its most frequent form—subacute encephalitis–an infected/inflamed brain as well as an infected nervous system. However, this is the form in which it most commonly exists. Unfortunately, the syndrome that is falsely considered typical–a bull’s eye rash, fever, positive Elisa test, and/or a swollen large joint–occurs in fewer then half of proven cases. Instead, Lyme borreliosis confirms itself in subtle to profound neuro-psychiatric symptoms, such as overriding confusion, loss of organizational skills, decreased concentration, memory loss, mood disorders, irritability, and unprovoked rages–to mention just a few. These symptoms can be very obvious to an experienced professional practicing in a Lyme-endemic area. However, cerebral-behavioral symptoms of neuro-Lyme remain invisible to those whose diagnoses are solely based on old-fashioned concepts limited only to the aforesaid doctor-viewed rashes, swollen knees with positive Elisa blood tests.
Blood tests completed by local labs most frequently show false negatives due to general laboratories’ inadequate understanding of proper diagnostic technique and choices of poor quality spirochetal samples on which to base tests. Of course, insurance companies prefer their negative tests. As mentioned, Lyme can rapidly go from Stage One (Early borreliosis) to Late (Tertiary) Stage disease following attachment of an infected deer tick’s or other vector’s bite so that quick and competent treatment are of the greatest importance. Later, accurate findings by sophisticated laboratories may be helpful, especially if Late Stage symptoms appear many years after the infection.
Over the years, I have been asked to create a compendium of my published and unpublished works on the subject of Borrelia’s neuropsychiatric epidemic. These literary contributions advocate for correction of medical neglect–the usually inadequate, sometimes cruel, diagnostic and treatment neglect experienced by victims of chronic Lyme borreliosis and its co-infections. I also have had articles published in an effort to attract attention from Organized Medicine—attention badly needed on behalf of a nearly invisible but serious epidemic that is more significant by far than anything this country has experienced since the Spanish Flu of 1918, the causative spirochete being less immediately deadly than was the virus of that epidemic, but deadly, nonetheless, cerebrally.
Sadly, Organized Medicine has mostly ignored or deserted the field of neuro-Lyme’s immense proportions. The American public rapidly is becoming jaundiced toward doctors’ lack of up-dated knowledge of spirochetal science and, having read the latest (indeed copious) peer-reviewed recent literature for themselves, are turning to other disciplines—even to veterinarians for accurate medical advice on the subject of Lyme disease and its co-infections. Veterinarians are more up to date on the diagnosis and treatment of human Lyme than the “Diagnose-and-treat-by-the-old-Guidelines” types of powerful but passé Academic physicians who cling to outdated medical dogma.
I have written about the rampant epidemiology of neuro-Lyme disease and its potent co-infections (especially the red cell parasite that causes babesiosis) and the fact that these are being systematically ignored, minimized, or distorted by this Nation’s overseeing Healthcare Agencies. Astoundingly, there are Agencies that, in ignorance or arrogance, may actively persecute the victims of such borrelial, pan-systematic illness, traumatizing parents and children as well as their treating physicians. There are those in authority who sponsor the official separation of children from parents whose only sin is that they persist in seeking help for their ailing children. Tragically, those authorities are empowered to permanently remove sick or partially healed young ones from their devoted families.
To their everlasting shame, medical authorities have stood by while innocent mothers have been sent to jail for insisting that their children were ill and again have stood by while the parent’s belief was verified by the death of their sick child while under State “care.” The rights of patients and their treating physicians have been trampled by governmental and insurance agencies in ways reminiscent of the era when AIDs was trivialized and its victims spurned as “psychosomatic.” Today’s infected millions worldwide show how wrong they were. The phenomenon of that epidemic is being repeated with the spread of Lyme borreliosis. My writing is an effort to illuminate this dark and now vast expanse of Medicine and to inspire activism and compassion for those patients who are suffering in agony while having to hear caretakers say, “I don’t know what you are worried about–you look just fine–maybe you are just depressed.” Or as one unknowing, dismissive and flippant doctor joked to a frightened patient who came to him for treatment and reassurance, “Well, we all have to die of something, sometime.”
A new paper on Neuro Lyme disease by Brain Fallon MD:
Check out this very comprehensive article on Neuro Lyme assessments by Robert Bransfield MD at:
Both are very interesting reads!
A lot of different papers on NEURO-COGNITIVE LYME DISEASE
NEUROLOGICAL MANIFESTATIONS OF LYME DISEASE IN CHILDREN
Dorothy M. Pietrucha, M.D., P.A.
3318 Route 33
Neptune, New Jersey 07753
CONTROVERSIES IN NEUROBORRELIOSIS
Audrey Stein Goldings, M.D.
Lyme Disease Conference
October 23, 1992
The objectives of this handout are to cover issues which are not even handedly addressed in the current literature on Lyme disease. I will:
1. present a practical approach for making the diagnosis of neuroborreliosis,
2. explore the other side of the post-Lyme syndrome (ie: the likelihood of chronic ongoing infection),
3. discuss the relationship between MS and Lyme,
4. critique the current regimens published for treating neuroborreliosis and
5. present my own approach which may differ from some leading authorities.
I hope to provide the reader with a broader understanding of neuroborreliosis so that he or she may better use current and evolving knowledge for clinical decision making.
J Neuropsychiatry Clin Neurosci 15:326-332, August 2003
© 2003 American Psychiatric Press, Inc.
Regional Cerebral Blood Flow and Cognitive Deficits in Chronic Lyme Disease
Brian A. Fallon, M.D., John Keilp, Ph.D., Isak Prohovnik, Ph.D., Ronald Van Heertum, M.D. and J. John Mann, M.D.
The average age of the 11 Lyme disease patients was 44.2 years (SD 12.4; range 19–63). The duration of symptoms was 59.5 months (SD 57.5; range 6–170), and the length of time since diagnosis was 18.9 months (SD 17.1; range 2–60). The duration of prior oral antibiotic treatment was 7.9 months (SD 7.3; range 0–19), and the duration of prior IV antibiotic treatment was 2.0 months (SD 1.1; range 1–4). The symptom history since the onset of Lyme disease included the following: memory loss (11/11), excessive fatigue (11/11), sleep disturbance (11/11), arthralgias (11/11), word-finding problems (10/11), headaches (9/11), radiculopathy (8/11), irritability and mood lability (8/11), recalled tick bite (5/11), physician diagnosed erythema migrans (4/11), and arthritis (4/11). Five of the 11 patients had had prior spinal taps, with 3 of the 5 revealing abnormal CSF results (2 ELISA positive for Borrelia burgdorferi and 1 with elevated protein). Eight of the 11 had had prior MRI scans, 4 of whom had abnormal results (one or more white matter hyperintensities).
What is striking in this study is the finding that there is an alteration of presumed white matter blood flow in the brains of patients who have chronic Lyme Disease and complain of cognitive deficits. Each of the 11 patients in our sample reported ongoing mild to severe cognitive problems that were confirmed on objective neuropsychological testing. As a group, when compared to published norms, the Lyme patients had significant deficits in verbal memory, which was demonstrated using both the Wechsler Memory Scale and the Buschke Selective Reminding Test. Memory deficits such as these are typically seen in samples of patients with Lyme encephalopathy.2,29
In conclusion, this cerebral blood flow study using Xenon133 demonstrated that patients with persistent Lyme encephalopathy have areas of decreased perfusion that appear to affect primarily the cerebral white matter. This decreased perfusion is associated with cognitive impairment. Future functional imaging studies that use more sophisticated tools (such as PET and/or fMRI) to examine biological and behavioral challenges need to focus on delineating white matter abnormalities in order to better characterize the pathophysiology of Lyme encephalopathy.
Dr. Fallon received support from a New York State Psychiatric Institute Research Support Grant & from the Lyme Disease Association to conduct this study.
Spirochetes on the Brain by Robert Bransfield
Any standard of diagnosis for late stage, chronic Lyme disease must incorporate the fact that it is a very complex disease with not only CNS, but also many other different presentations in its later stages. Therefore, the diagnosis of chronic Lyme disease is considered by personally perform¬ing a thorough and relevant history and examina¬tion, ordering and/or reviewing relevant labora¬tory tests in the proper context, and exercising sound clinical judgment by a licensed physician who is knowledgeable and experienced about chronic Lyme disease and is held accountable for his decisions.