NEUROLOGICAL RARITIES

Lyme disease presenting as multiple
ischaemic strokes
Sui Li, Michal Vytopil, Kinan Hreib, Donald E Craven

Department of Neurology, Lahey
Hospital & Medical Center,
Burlington, Massachusetts, USA
Correspondence to
Dr Sui Li, Department of
Neurology, Lahey Hospital &
Medical Center, 41 Burlington
Mall Rd, Burlington, MA 01805,
USA; Sui.Li@Lahey.org
Accepted 18 March 2015

ABSTRACT
A 46-year-old man presented with recurrent left
hemiparesis and headache. MRI of brain showed
an acute right pontine and subacute right
thalamic infarcts and MR angiogram showed
multiple intracranial arterial stenoses, suggesting
cerebral vasculopathy. There was a cerebrospinal
fluid lymphocytic pleocytosis with Borrelia
burgdorferi antibodies. Central nervous system
Lyme disease occasionally presents with
ischaemic strokes; this case is unusual in showing
vasculopathy on brain imaging, supporting
meningovasculitis as the likely mechanism.

INTRODUCTION
Lyme disease (from Borrelia burgdorferi
infection (figure 1)) affecting the
central nervous system (CNS Lyme)
may cause meningitis, facial nerve palsy,
headache, paraesthesias, fatigue, cognitive disturbance and polyradiculitis.1
CNS Lyme is rare but occasionally
causes ischaemic stroke, presumably
due to intracranial vasculitis or vasculopathy.2 This has been well reported in
Europe3–12 but is surprisingly rare in
North America, presumably because of
genetic differences in the species of
Borrelia between the two regions.13 14
We report a man from southern New
England, USA, with multiple strokes in
the setting of CNS Lyme and review
the current literature.

To cite: Li S, Vytopil M,
Hreib K, et al. Pract Neurol
Published Online First: [ please
include Day Month Year]
doi:10.1136/practneurol2014-001072

CASE REPORT
A 46-year-old man from Rhode Island,
USA, presented in December 2011 with
acute onset left-sided weakness and
numbness. He reported removing several
ticks from his dogs over the summer and
fall of that year in his rural residence, but
did not recall any specific episode of tick
exposure or skin rash on himself. He had
a history of hypertension and hyperlipidaemia. MR scan of brain showed an acute
right thalamic infarction and MR cerebral
angiography showed decreased flow in

the right middle cerebral artery territory.
A transoesophageal echocardiogram,
carotid ultrasound scan and hypercoagulable panel were normal.
He presented again to the emergency
department twice in the following
3 weeks. At the first visit he reported
right-sided sharp throbbing headache;
CT scan of head was normal and he was
discharged home. On the second visit he
had transient dysarthria, left-sided weakness and numbness, and left hand incoordination. Repeat MR scan of brain
showed interval evolution of the right
thalamic stroke and a new area of acute
infarction in the right paracentral pons
(figure 2). MR cerebral angiography
showed attenuation of the distal right M1
segment of the middle cerebral artery
with scattered stenoses of the Sylvian
branches, and irregularities involving
both A1 segments of the anterior cerebral
arteries (figure 3), all confirmed on CT
angiography (not shown).
Cerebrospinal fluid (CSF) showed
lymphocytic pleocytosis (100 leucocytes/
mm3, 90% lymphocytes), zero red blood
cells, elevated protein (180 mg/dL),
normal glucose (41 mg/dL) and five

Figure 1

Borrelia burgdorferi.

Li S, et al. Pract Neurol 2015;0:1–5. doi:10.1136/practneurol-2014-001072

1

NEUROLOGICAL RARITIES

Figure 2 Acute pontine and subacute thalamic strokes. Above: MR scan of brain (fluid-attenuated inversion recovery sequence)
showing hyperintensity of the right internal capsule posterior limb and thalamus consistent with previous stroke. Below: MR scan of
brain (diffusion-weighted imaging and apparent diffusion coefficient maps) showing diffusion restriction in right paracentral pons
consistent with acute stroke.

oligoclonal bands unique to the CSF. A CSF ELISA for
total antibodies against B. burgdorferi was positive
(5.71 LIV, normal <0.99). CSF western blot confirmed
anti-B. burgdorferi antibodies (IgM band against 23 kd
protein, IgG bands against 66 kd, 58 kd, 45 kd, 41 kd,
39 kd, 30 kd, 28 kd, 23 kd and 18 kd proteins). An
extensive autoimmune and infectious laboratory
workup was negative (box 1). He was treated with
4 weeks of intravenous ceftriaxone followed by
4 weeks of intravenous penicillin G. Subsequent CSF
showed gradual resolution of the pleocytosis, falling
protein levels, and clearance of IgM bands and
decrease in IgG bands (table 1). Eight months after his
diagnosis, repeat MR angiography showed significant
interval improvement of persistent intracranial arterial
2

irregularities (figure 3). He still has mild residual left
hand weakness. Repeat MR scan of brain showed no
new silent ischaemic lesions. We did not test for tuberculosis, given the low clinical suspicion; his spontaneous improvement without proper treatment would
have made CNS tuberculosis extremely unlikely.
DISCUSSION
Lyme disease is caused by infection with B. burgdorferi, a spirochaete that spreads via the bite of infected
ticks. It is the most common tickborne infection in
the USA and Europe. Borrelia is a heterogeneous
group of spirochaetes. Most Lyme disease cases can
be accounted for by three species: B. burgdorferi sensu
stricto is responsible for infections in North America;
Li S, et al. Pract Neurol 2015;0:1–5. doi:10.1136/practneurol-2014-001072

NEUROLOGICAL RARITIES

Figure 3 Multiple areas of intracranial stenoses before and after treatment. MR angiogram of brain shows multiple areas of
attenuation and scattered stenoses involving bilateral anterior cerebral arteries and the right middle cerebral artery. Repeat MR
angiogram 8 months after treatment shows significant interval improvement of focal stenoses.

by comparison, B. burgdorferi sensu lato strains,
Borrelia garinii and Borrelia afzelii are more predominant in Europe and Asia.
There are differences between American and
European Lyme infections. Pachner et al isolated B.
burgdorferi from the CSF of American patients and B.
garinii or B. afzelii from European patients. These
spirochaetes injected into animals caused different
disease manifestations, attributed to genetic variations
between the strains.13 14 While the strains causing
American Lyme disease induced a more robust inflammatory response in non-nervous tissues, those responsible for European Lyme better resisted the host’s
immune responses and more likely persisted in the
nervous system.13 The pattern of neurological involvement also differed between the two groups of
animals, confirming the clinical observation that CNS

Box 1

Negative autoimmune and infective workup

Hepatitis B and C serology
HIV 1 and 2 antibodies
Anaplasma Phagocytophilum antibody
Babesia microti antibody
Ehrlichia chaffeensis antibody
C reactive protein
Antineutrophil cytoplasmic antibody
Sjögren’s antibodies (anti-Ro, anti-La)
Rheumatoid factor
Anti-DNA antibody (native)
CSF herpes simplex, cytomegalovirus and varicella zoster
by PCR
CSF cryptococcal antigen
CSF syphilis serology

Li S, et al. Pract Neurol 2015;0:1–5. doi:10.1136/practneurol-2014-001072

Lyme manifests differently in Europe and in the USA.
American CNS Lyme usually presents as aseptic meningitis, often with erythema migrans rashes, and
shows higher rates of seropositivity; whereas
European CNS Lyme typically presents as a painful
polyradiculitis—Bannwarth’s syndrome—rarely with a
preceding erythema migrans rash and is more likely to
induce intrathecal antibodies.
Stroke in the setting of CNS Lyme disease is rare.
Hammers-Berggren et al10 found only 1 of 281
patients admitted to a hospital in Sweden with cryptogenic stroke had active CNS Lyme; they concluded
there was little value in screening for Lyme serology in
patients with acute stroke. Nonetheless, there have
been multiple reports of CNS Lyme manifesting as
stroke, particularly in European and in younger
patients.3–12 Topakian et al4 reported two cases of
cerebral vasculitis and stroke due to CNS Lyme and
reviewed 15 previously published cases, 14 from
Europe and 1 from the USA, noting that most patients
had a prodromal stage lasting several weeks to
months of non-specific complaints, such as headache,
fatigue, difficulty concentrating, nausea and
vomiting. Erythema migrans preceding stroke was rare,
reported in only two cases, including the one
American patient.
There have been only two reported cases of cerebral
vasculitis and stroke in the setting of CNS Lyme
acquired in the USA. In 1990, Brogan et al15 described
a 37-year-old woman, 10 days postpartum, presenting
with recurrent thunderclap headache; there was no
CSF pleocytosis and in retrospect, reversible cerebral
vasoconstriction syndrome seems the likely diagnosis.
The second case, reported by Reik, was a 56-year-old
woman with multiple strokes 18 months after antibiotic treatment for Lyme infection with facial
3

NEUROLOGICAL RARITIES
Table 1

Cerebrospinal fluid (CSF) studies
Lyme antibody IgM*
(number of bands)

CSF leucocytes†
(cells/mm3)

CSF protein
(mg/dL)

January 2012
5.71
9
February 2012
4.90
6
March 2012
4.56
6
June 2012
2.78
5
August 2012
Not done
6
*Confirmatory testing by western blot.
†Per cent of lymphocytes ranged 90–97 on all occasions.

1
1
0
0
0

100
25
21
6
2

180
121
100
99
80

neuritis;11 there was lymphocytic pleocytosis with
intrathecal production of Lyme antibodies. Although
they did not report cerebral vascular imaging, Lyme
meningovasculitis appeared to the likely mechanism of
stroke.
The pathophysiology of stroke in CNS Lyme is probably mediated by an inflammation of intracranial vasculature with subsequent narrowing and decreased blood
flow. Whether this vasculopathy originates from direct
infiltration of the vessel wall by spirochaetes, spread of
inflammation from adjacent meninges or from deposition of immune complexes, remains unclear. In our
patient, there were persistent arterial irregularities in the
face of CSF normalisation 8 months after treatment,
suggesting that the impact of inflammation on the arteries is permanent. Alternatively, one could speculate that
the inflammatory mechanism preferentially involved
arterial segments already affected by other processes,
such as atherosclerosis.
Our patient presented very similarly to European
cases of stroke in CNS Lyme. He had no preceding
erythema migrans rash and produced intrathecal
Lyme antibodies. Therefore, this clinical constellation
is not unique to infection by B. garinii or B. afzelii but
can be occasionally encountered in American infection
caused by B. burgdorferi sensu stricto. The same is
true for Bannwarth’s syndrome; although thought to
be a unique clinical hallmark of B. garinii infection, it
also can occur in patients with infection acquired in
the USA.16
Our patient’s lymphocytic pleocytosis persisted
7 months following antibiotic treatment, not unlike
other cases with reported follow-up CSF examination.4 6 Whether post-treatment pleocytosis represents an ongoing infection requiring another course of
antibiotics, or possibly a secondary autoimmune phenomenon, is debateable. Several authors have advised
against additional treatment if the clinical course is
favourable.4 6 Despite the lack of evidence to support
repeat treatment of patients with persistent symptoms
of Lyme disease,17 we gave a second course of intravenous antibiotics because of persistent headache and
pleocytosis of 25 white blood cells/mm3 on the first
post-treatment CSF evaluation 1 month after the
diagnosis.

CONCLUSION
In summary, clinicians should consider a diagnosis of
CNS Lyme vasculitis in patients with cryptogenic
strokes, particularly those who are younger, have
prominent headache, have evidence of vasculopathy
on cerebrovascular imaging and those who come from
areas where Lyme disease is endemic. A CSF abnormality is a prerequisite for the diagnosis of Lyme CNS
vasculitis.

Date

4

Lyme antibody
index

Lyme antibody IgG*
(number of bands)

Competing interests None.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally
peer reviewed. This paper was reviewed by Ashwin Pinto,
Southampton, UK.

REFERENCES
1 Logigian EL, Kaplan RF, Steere AC. Chronic neurologic
manifestations of Lyme disease. N Engl J Med
1990;323:1438–44.
2 May EF, Jabbari B. Stroke in neuroborreliosis. Stroke
1990;21:1232–5.
3 Van Snick S, Duprez TP, Kabamba B, et al. Acute
ischaemic pontine stroke revealing lyme neuroborreliosis
in a young adult. Acta Neurol Belg 2008;108:103–6.
4 Topakian R, Stieglbauer K, Nussbaumer K, et al. Cerebral
vasculitis and stroke in Lyme neuroborreliosis. Two case
reports and review of current knowledge. Cerebrovasc Dis
2008;26:455–61.
5 Sparsa L, Blanc F, Lauer V, et al. Recurrent ischemic strokes
revealing Lyme meningovascularitis. Rev Neurol (Paris)
2009;165:273–7.
6 Heinrich A, Khaw AV, Ahrens N, et al. Cerebral vasculitis as the
only manifestation of Borrelia burgdorferi infection in a
17-year-old patient with basal ganglia infarction. Eur Neurol
2003;50:109–12.
7 Klingebiel R, Benndorf G, Schmitt M, et al. Large cerebral
vessel occlusive disease in Lyme neuroborreliosis.
Neuropediatrics 2002;33:37–40.
8 Defer G, Levy R, Brugiéres P, et al. Lyme disease presenting as
a stroke in the vertebrobasilar territory: MRI. Neuroradiology
1993;35:529–31.
9 Rey V, Du Pasquier R, Muehl A, et al. Multiple ischemic
strokes due to Borrelia garinii meningovasculitis. Rev Neurol
(Paris) 2010;166:931–4.

Li S, et al. Pract Neurol 2015;0:1–5. doi:10.1136/practneurol-2014-001072

NEUROLOGICAL RARITIES
10 Hammers-Berggren S, Gröndahl A, Karlsson M, et al.
Screening for neuroborreliosis in patients with stroke. Stroke
1993;24:1393–6.
11 Reik L Jr. Stroke due to Lyme disease. Neurology 1993;43:
2705–7.
12 Lebas A, Toulgoat F, Saliou G, et al. Stroke due to lyme
neuroborreliosis: changes in vessel wall contrast enhancement.
J Neuroimaging 2012;22:210–12.
13 Pachner AR, Steiner I. Lyme neuroborreliosis: infection,
immunity, and inflammation. Lancet Neurol
2007;6:544–52.

Li S, et al. Pract Neurol 2015;0:1–5. doi:10.1136/practneurol-2014-001072

14 Pachner AR, Dail D, Bai Y, et al. Genotype determines
phenotype in experimental Lyme neuroborreliosis. Ann Neurol
2004;56:361–70.
15 Brogan GX, Homan CS, Viccellio P. The enlarging clinical
spectrum of Lyme disease: Lyme cerebral vasculitis, a new
disease entity. Ann Emerg Med 1990;19:572–6.
16 Donaldson JO, Lewis RA. Lymphocytic meningoradiculitis in
the United States. Neurology 1983;33:1476–9.
17 Klempner MS, Hu LT, Evans J, et al. Two controlled trials of
antibiotic treatment in patients with persistent symptoms and a
history of Lyme disease. N Engl J Med 2001;345:85–92.

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