38

Przegl¹d Lekarski 2007 / 64 / Suplement 3

M. Kaciñski et al.

ORIGINAL PAPERS – PRACE ORYGINALNE

CNS Lyme disease manifestation in children

Kliniczna manifestacja neuroboreliozy u dzieci

Marek KACIÑSKI

Anna ZAJ¥C

Barbara SKOWRONEK-BA£A

S³awomir KROCZKA

Aleksandra GERGONT

Alicja KUBIK

Department of Pediatric Neurology,

Jagiellonian University, Krakow, Poland

Additional key words:

neuroborreliosis

transverse myelitis

acute ataxia

seizures

children

Dodatkowe s³owa kluczowe:

neuroborelioza

poprzeczne zapalenie rdzenia krêgowego

ostra ataksja

napady padaczkowe

dzieci

Adres do korespondencji/

Corresponding author:

Marek Kaciñski

Department of Pediatric Neurology

Wielicka St. 265, 30-663 Krakow, Poland

Fax: [phone],

e-mail: [e-mail]

Background: Neurological symp-

toms develop in 10-20% of children

with borreliosis. Aim of the study: It

was a presentation of clinical manifes-

tation of neuroborreliosis in children.

Material and methods: Children with

neuroborreliosis and other neurologi-

cal diseases were admitted to the Uni-

versity Hospital during 2005-2006 with-

out any selection. Of these 9 patients,

there were seven males and two fe-

males, ranging in age between 3-17

years. Neurological diagnostic was

performed using ELISA Biomedica kit

and western blot bands. A 2-6 week

sequential treatment with either iv

ceftazidime or amoxicillin and oral

doxycycline or amoxicillin was pro-

vided. Children were monitored regu-

larly during the next 4-24 months. Re-

sults: The 9 children with borreliosis

constitute 0,53% of the pediatric neu-

rology department’s patients. The clini-

cal manifestation of LD were usual and

unusual from patient to patient. They

included three cases of facial nerve

paralysis (with bilateral paralysis in

one case). In two cases, they included

transverse myelitis and in a single

case, hemiparesis, meningitis and

acute ataxia. Typically, other patients

with early stage borreliosis first mani-

fest focal seizures, raising the suspi-

cion that borreliosis could be respon-

sible for triggering seizures. The anti-

biotic treatment was successful in 7

patients and only partially effective in

2 children with facial nerve paralysis.

Conclusions: The most common

symptom of neuroborreliosis in chil-

dren is motor dysfunction. Acute

ataxia may be a clinical presentation

of neuroborreliosis. It is probable that

borreliosis triggers seizures in chil-

dren with EEG abnormalities.

Wprowadzenie: Objawy neurolo-

giczne wystêpuj¹ u 10-20% dzieci cho-

rych na boreliozê. Cel pracy: By³o nim

zaprezen-towanie klinicznych postaci

neuro-boreliozy u dzieci. Materia³ i

metody: Dzieci z neuro-borelioz¹ i in-

nymi chorobami uk³adu nerwowego

by³y przyjmowane do Uniwersyteckie-

go Dzieciêcego Szpi-tala w latach

2005-2006 bez ¿adnej selekcji. Wœród

9 dzieci by³o 7 ch³o-pców i 2 dziew-

czynki w wieku 3-17 lat. Rozpoznanie

stawiano na podstawie wyników te-

stów ELISA Biomedica i western blot.

Stosowano 2-6 tygo-dniowe leczenie

przy u¿yciu cefta-zydymu albo amok-

sycyliny w formie do¿ylnej i doksycy-

kliny albo amoksy-cyliny doustnie.

Stan dzieci monitoro-wano przez na-

stêpne 4-24 miesi¹ce. Wyniki: 9 dzieci

z borelioz¹ sta-nowi³o 0,53% spoœród

wszystkich pacjentów Kliniki Neurolo-

gii Dzie-ciêcej. U poszczególnych dzie-

ci manifestacja neuroboreliozy by³a

powszechnie spotykana albo rzadka.

U 3 z nich by³o to pora¿enie nerwu twa-

rzowego (w 1 przypadku obu-stronne).

U dwojga dzieci poprzeczne zapalenie

rdzenia krêgowego, a u pojedynczych

dzieci niedow³ad po³owiczy, zapalenie

opon mózgowo-rdzeniowych i ostra

ataksja. U innego pacjenta we wcze-

snym stadium boreliozy wyst¹pi³ na-

pad drgawek ogniskowych, co nasu-

wa pytanie o jej udzia³ w wywo³aniu

napadów padaczkowych. Zastosowa-

ne leczenie by³o w pe³ni skuteczne u 7

dzieci i czêœciowo skuteczne u dwoj-

ga dzieci z pora¿eniem nerwu twarzo-

wego. Wnioski: Najczêstszymi objawa-

mi neuroboreliozy u dzieci s¹ zaburze-

nia ruchowe. Kliniczn¹ postaci¹ neu-

ro-boreliozy mo¿e byæ ostra ataksja.

Borelioza mo¿e prawdopodobnie wy-

wo³ywaæ napady padaczkowe u dzieci

z patologicznym zapisem EEG.

Introduction

Borreliosis (Lyme disease, LD) is

currently the most common tick-borne

infection. Children attending a „forest

kindergarten” have a 2,8 times greater

risk of experiencing tick bites and a 4,6

times greater risk of suffering from bor-

reliosis as compared to children enrol-

led in a conventional kindergarten [22].

In children living in endemic areas, obse-

rvations showed increased incidence of

overdiagnosis and overtreatment of LD

using standardized CDC diagnostic criteria

[15]. In some cases, the disease resolves

spontaneously, but usually the course is cli-

nically progressive beginning with initial

symptoms of erythema migrans [6]. The ear-

ly stages of LD are frequently accompanied

39

Przegl¹d Lekarski 2007 / 64 / Suplement 3

by an increase in serum/CSF IgM antibodies

against spirochete, while late stages are ge-

nerally associated with high levels of IgG

antibodies [5,8].

10-20% of children with LD develop neu-

rological symptoms, among which the most

frequent are meningitis and facial nerve

palsy [1,6,9]. Headaches, pseudotumor ce-

rebri, transverse myelitis, limb pain, nonpa-

ralytic poliomyelitis, as well as optic neuri-

tis, sensorineural hearing loss, and vestibu-

lar neuronitis, are rarely manifested in neu-

roborreliosis [10,13,14,16,17,19,20,21].

Children with CNS LD presented with signi-

ficantly more cognitive deficits and psychia-

tric disturbances, resulting in psychosocial

and academic impairment [18]. Meta-ana-

lysis provides strong evidence that some

patients with LD continue to experience fa-

tigue, musculoskeletal pain, and neuroco-

gnitive difficulties for years after their illness

despite antibiotic treatment [4].

The objectives of this study were to es-

tablish how often neuroborreliosis is diagno-

sed in patients at the University Hospital,

Krakow and how clinical types of this dise-

ase can occur at one institution during such

a brief time.

Material and Methods

From January 1, 2005 to December 31, 2006 in the

Department of Pediatric Neurology Jagiellonian Univer-

sity in Krakow, 1690 children with different neurological

diseases were hospitalised. LD was diagnosed in 9 of

them, (7 boys and 2 girls) between the ages of 3-17 years.

Clinical symptoms that occurred in these patients prior

to the hospitalization are presented in table I.

Each patient was carefully examined and diagnosed

by two pediatric neurologists during the time of their di-

agnosis, and subsequently followed up by the same phy-

sicians within the next 4-24 months. LD diagnosis was

made using ELISA Biomedica kits and determined by

the presence of western blot bands. Intravenous and oral

antibiotic therapy was administered due to significant

neurological symptoms. 2-4 weeks of iv therapy with

ceftazidime was administered to 7 of the children, and 3

weeks of iv therapy with amoxicillin was given to one

child. Two weeks of oral therapy with doxycycline was

provided for 5 of the children and two weeks of amoxy-

cyline was given to the remaining child.

Results

9/1690 (0,53%) of hospitalized children

fulfilled the criteria of active LD. In 5 of them,

tic bites were evident 2-12 weeks prior to

clinical neurological symptoms (table I). The

most common clinical symptom in 6/9 of the

children was motor paralysis, facial nerve

paralysis in three of them (bilateral in one

case), transverse myelitis in two of them and

hemiparesis in the last. Furthermore menin-

gitis and acute ataxia were diagnosed in two

other child. A 4-year-old boy, who experien-

ced his first left sided clonic seizure was also

included to the CNS LD group. Focal seizu-

res occurred in his case 5 weeks after a tick

bite. However, mood disturbances with non-

specific EEG abnormalities started as early

as infancy in this child (table II).

Serum and cerebrospinal fluid in all chil-

dren showed high levels of borrelia antibo-

dies (>30 Borelia Biomedica Unit) and the

presence of western blot bands. Cytosis in

four children was slightly elevated (21-57 in

mm

3

), but only one of them presented me-

ningitis. In two others, transverse myelitis

and in another, facial nerve paralysis was

diagnosed. CNS imaging was normal in 8

children, while in the case of the 15-year-

old boy (case No 3) with triparesis and up-

per limb pain, MRI showed dilatation of the

spinal cord with pleocytosis and cerebrospi-

nal fluid protein level (1,6 g/l) elevation. With

2-6 weeks of antibiotic therapy, a complete

recovery was obtained in 7 children. Howe-

ver in the other two children with facial ne-

rve paralysis only partial recovery was po-

ssible (table II).

Discussion

Six out of nine patients in the analysed

group presented motor symptoms. In three

of them, peripheral facial nerve paralysis

was diagnosed, which is most likely a result

of the particular vulnerability of this nerve.

Its long intraosseus course and injury by

inflammatory oedema in the facial canal

decides paralysis of this nerve. An uncom-

mon CNS LD manifestation is bilateral fa-

cial nerve paralysis, which was observed in

one of our own patients [7].

Hattingen et al. revealed strong enhan-

cement of the cervical nerve roots on con-

trast-enhanced T1-weighted images in two

cases of cervical spinal cord neuroborrelio-

sis [9]. We did not observe similar root chan-

ges in patients with triparesis and cervical

cord involvement (case No 3), only spinal

cord dilatation. Klingebiel et al. described

LD hemiparesis as a result of an occlusive

disease of the large vessels. Similar patho-

logy may be present in our patient (case No

2) with hemiparesis [12].

Only one child in the analysed group

suffered clinical meningitis, while in recent

publications, meningitis was the most com-

monly observed LD manifestation [1, 6, 17].

Pleocytosis was also slightly increased in

three other patients with different clinical

syndromes. We have not found any case of

optic neuritis or sensorineural hearing symp-

tomatology, which is still a clinical dilemma

in neuroborreliosis [10, 16, 20]. None of the

patients in our group suffered persistent

headaches similar to those observed in pa-

tients participating in other studies [14].

Whether or not borreliosis can trigger

epileptic activity in the early stages of the

disease, is still an unresolved clinical pro-

blem. The coincidence of a tic bite 5 weeks

prior to the onset of an initial epileptic se-

izure was observed in a 4 year old boy. Tre-

atment with oral doxycycline in this case

ceased borrelia invasion with erythema mi-

Table I

Characteristic of the children with neuroborreliosis.

o

N

t

n

ei

t

a

P

e

g

A

r

e

d

n

e

g

/)

s

r

a

e

y

(

y

r

o

ts

ih

la

ci

g

ol

o

r

u

e

N

m

o

rf

)

s

k

e

e

w

(

e

m

i

T

n

oi

t

a

zi

la

ti

p

s

o

h

o

t

e

ti

b

ci

t

s

m

o

t

p

m

y

s

la

ci

g

ol

o

r

u

e

N

)

n

oi

t

a

r

u

d

f

o

s

y

a

d

(

1

M

/

7

1

la

m

r

o

N

?

d

n

a

s

g

el

e

h

t

f

o

si

s

yl

a

r

a

P

)

3

(

s

r

e

tc

ni

h

p

s

2

M

/

6

1

la

m

r

o

N

0

1

e

di

s

tf

el

t

n

e

tti

m

r

e

t

ni

,

ni

a

p

k

c

a

B

)

0

1

(

s

s

e

n

k

a

e

w

3

M

/

5

1

la

m

r

o

N

2

1

e

h

t

f

o

ni

a

p

e

t

u

c

a

,s

is

e

r

a

pi

r

T

)

4

1

(

b

m

il

r

e

p

p

u

4

F

/

5

1

la

m

r

o

N

?

)

3

(

si

s

yl

a

r

a

p

la

ic

a

f

t

h

gi

R

5

M

/

8

la

m

r

o

N

?

)

2

(

y

sl

a

p

la

ic

a

f

t

h

gi

R

6

F

/

6

la

m

r

o

N

2

)

3

(

si

s

yl

a

r

a

p

la

ic

a

f

la

r

e

t

al

i

B

7

M

/

4

la

m

r

o

N

4

)

7

(

ni

a

p

k

c

e

N

8

M

/

4

s

e

c

n

a

b

r

u

ts

id

d

o

o

M

s

ei

til

a

m

r

o

n

b

a

G

E

E

5

)

1

(

s

e

r

u

zi

e

s

ci

n

ol

c

e

di

s

tf

e

L

9

M

/

3

la

m

r

o

N

?

)

2

(

ai

x

a

t

a

e

t

u

c

A

Table II

Therapy and clinical evaluation in children with neuroborreliosis.

t

n

ei

t

a

P

o

N

a

t

a

d

n

oi

t

a

ni

m

a

x

e

la

ci

s

y

h

P

)

s

k

e

e

w

(

y

p

a

r

e

h

t

la

it

n

e

u

q

e

S

e

m

o

c

t

u

o

la

ci

ni

l

C

p

u

-

w

ol

lo

F

)

s

h

t

n

o

m

(

1

e

m

o

r

d

n

y

s

n

oi

s

el

la

ni

p

S

)

2

(

e

m

id

iz

a

tf

e

C

vi

)

2

(

e

ni

lc

y

c

y

x

o

D

la

r

o

la

m

r

o

N

4

2

2

si

s

e

r

a

pi

m

e

h

tf

e

L

)

3

(

ni

lli

ci

x

o

m

A

vi

)

2

(

e

ni

lc

y

c

y

x

o

D

la

r

o

la

m

r

o

N

7

3

)r

e

p

p

u

t

h

gi

r

d

n

a

s

r

e

w

ol

(

si

s

e

r

a

pi

r

T

)

3

(

e

m

id

iz

a

tf

e

C

vi

)

2

(

ni

lli

ci

x

o

m

A

la

r

o

la

m

r

o

N

4

4

y

sl

a

p

la

ic

a

f

t

h

gi

R

)

4

(

e

m

id

iz

a

tf

e

C

vi

)

2

(

e

ni

lc

y

c

y

x

o

D

la

r

o

la

m

r

o

N

6

1

5

y

sl

a

p

la

ic

a

f

t

h

gi

R

)

3

(

e

m

id

iz

a

tf

e

C

vi

)

2

(

e

ni

lc

y

c

y

x

o

D

la

r

o

si

s

e

r

a

p

dl

i

M

4

1

6

y

sl

a

p

la

ic

a

f

la

r

e

t

al

i

B

)

3

(

e

m

id

iz

a

tf

e

C

vi

si

s

e

r

a

p

dl

i

M

6

7

si

ti

g

ni

n

e

M

)

3

(

e

m

id

iz

a

tf

e

C

vi

la

m

r

o

N

8

8

la

m

r

o

N

e

ni

p

e

z

a

m

a

b

r

a

C

)

2

(

e

ni

ly

c

y

x

o

D

la

r

o

y

s

p

el

ip

E

5

9

ai

x

a

t

a

e

t

u

c

A

)

3

(

e

m

id

iz

a

tf

e

C

vi

la

m

r

o

N

8

40

Przegl¹d Lekarski 2007 / 64 / Suplement 3

M. Kaciñski et al.

grans, similarly to Bonnetblanc’s observa-

tion [3]. Results of LD treatment with cefta-

zidime observed in our hospitalized cases

were excellent and similar to results of ce-

ftriaxone therapy. However facial palsy, in

those cases, did not resolve completely [11].

Patients followed up within the subsequent

6-8 months showed complete recovery in

one case and partial recovery in two other

cases of patients with facial palsy. These

results coincide with the clinical and EMG-

ENG observations of Bagger-Sjoback et al.

[2]. Unusual CNS LD manifestation was

acute ataxia, with rapid recovery upon anti-

biotic therapy.

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