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Kawasaki Disease
With Predominant
Central Nervous
System Involvement
Brahim Tabarki, MD,
Abdallah Mahdhaoui, MD,
Habib Selmi, MD, Moncef Yacoub, MD,
and Ahmed S. Essoussi, MD
A 4-year-old female was hospitalized with clinical and
electroencephalographic evidence of acute encephalop-
athy. Five days later the classic signs of Kawasaki
disease appeared. The neurologic outcome in this fe-
male was poor despite early treatment with immuno-
globulin. Like many other vasculitidies, Kawasaki dis-
ease can have predominant neurologic symptoms as
the initial presentation and during the subsequent
evolution of the condition. © 2001 by Elsevier Science
Inc. All rights reserved.
Tabarki B, Mahdhaoui A, Selmi H, Yacoub M, Essoussi
AS. Kawasaki disease with predominant central nervous
system involvement. Pediatr Neurol 2001;25:239-241.
Introduction
Kawasaki disease is an acute vasculitis of unknown
etiology with varied clinical manifestations. Central ner-
vous system involvement occurs in 0.4% of children with
this disease and include seizures, ataxia, cerebral infarc-
tion, and subdural effusion [1-6]. A young female patient
in whom disturbance of consciousness, seizures, and
hemiplegia preceded the classic symptoms of Kawasaki
disease is presented. The patient exhibited severe neuro-
logic sequelae despite early treatment with intravenous
immunoglobulin.
Case Report
A previously healthy 4-year-old female was admitted to hospital after
two focal seizures of less than 5 minutes. She had had a 2-day history of
fever and anorexia, and a 1-day history of progressive deterioration of
consciousness. On examination her temperature was 39.5°C, heart rate
135 beats/minute, respiratory rate 22 breaths/minute, and blood pressure
115/60 mm Hg. Weight, height, and head circumference were all within
the normal range. She displayed generalized hypotonia, coma, but with
eye opening to painful stimuli, and motor responsiveness in flexion
triggered only by painful stimuli. She had a left-sided hemiparesis with
left extensor plantar reflexes. Deep tendon reflexes were normal. There
was mild erythema of the pharynx and a rash involving the upper chest.
Organomegaly was not detected. An electroencephalogram revealed
diffuse slow waves particularly on the right side. Computed tomographic
(CT) scan, analysis of cerebrospinal fluid (CSF), and optic fundi were
normal. Other laboratory findings included the following: leukocyte
count 10,800 cells/mm
3
with 70% polynuclear leukocytes; hemoglobin
level 110gm/L; and a platelet count of 325,000/mm
3
. The C-reactive
protein level was 4.8 gm/L (normal less than 0.6 gm/L). The patient was
treated with phenobarbital, cefotaxime, acyclovir, and the usual measures
to minimize cerebral edema.
Between days 3 and 5 of illness, the patient remained comatose with
hemiparesis and continued to have fever. She had several episodes of
right focal seizures with secondary generalization that were controlled by
intravenous phenobarbital and clonazepam. On day 4 of illness, the
maculopapular rash spread to most of her body and she developed
bilateral conjunctivitis. Electoencephalogram illustrated diffuse slow
waves associated with bilateral paroxysmal discharges. An electro-
cardiogram and echocardiogram were normal.
On day 6 of illness, she remained in coma. She had injected palms,
swelling of the extremities, and injected limbs. An echocardiogram
revealed bilateral coronary artery aneurysms (5-mm diameter). She was
then diagnosed with Kawasaki disease; intravenous immunoglobulin (1
gm/kg per day for 2 days) and acetysalicyclic acid were administered.
She became afebrile 2 days after immunoglobulin therapy. On day 10 of
illness, there was spontaneous opening of the eyes but no response to
external stimuli. She remained hemiparetic and continued to have mostly
focal seizures 2-3 times daily. Treatment with sodium valproate and
clobazam was started. The level of consciousness gradually rose, but her
speech was still impaired. Compared with cognitive function, her motor
function demonstrated better recovery. Three months after the onset of
illness, and after a period of rehabilitation, the hemiplegia relented, and
she was able to stand and walk alone. Twelve months later she displayed
autistic behavior. She was able to utter only two words. She was
occasionally able to follow simple commands, but most of the time it was
not possible to communicate with her. She was unable to eat alone. She
always experienced one to two generalized seizures per month. The last
electroencephalogram revealed diffuse slow waves.
CSF analysis (including protein electrophoresis) remained normal on
day 7 and 17 of illness. Results of bacteriologic and viral investigations
(blood, CSF, and urine) were negative. Biochemical and metabolic
investigations, including blood glucose, electrolytes, ammonia, amino
acid chromatography, and organic acid chromatography were normal.
Auditory-evoked potentials revealed bilateral sensorineural hearing loss.
CT scan (day 8), magnetic resonance imaging (MRI) of the brain, and
From the Services de Pe´diatrie et de Cardiologie; Hoˆpital
Farhat-Hached; Sousse, Tunisia. Communication should be addressed to:
Dr. Tabarki; Saint-Luc University Hospital; Hippocrate Avenue 10;
1200 Brussels, Belgium.
Received November 29, 2000; accepted April 3, 2001.
239© 2001 by Elsevier Science Inc. All rights reserved. Tabarki et al: Kawasaki Disease and Encephalopathy
PII S0887-8994(01)00290-9 ●0887-8994/01/$—see front matter
magnetic resonance angiography (day 25) were normal (Fig 1A). Serial
echocardiography over the ensuing 8 months indicated gradual reduction
in the size of the coronary artery aneurysms. Auditory brainstem
response was normal at month 10. MRI scan of the brain at month 12
depicted a diffuse and severe cerebral atrophy, characterized by enlarge-
ment of sulci and ventricular dilatation (Figs 1B and 2).
Discussion
Acute neurologic diseases that include coma and sei-
zures during or immediately after an episode of infection
are common in children. Most of these children have CNS
infection. This patient had a severe encephalopathy in the
context of Kawasaki disease. The investigations per-
formed excluded the common causes for such a clinical
presentation, such as infections and metabolic diseases.
Thus this patient’s encephalopathy was considered as
specifically related to Kawasaki disease. The association
between acute encephalopathy and Kawasaki disease has
been reported in only a few children. Although pro-
nounced irritability, lethargy, and aseptic meningitis are
quite common in Kawasaki disease [3,7], other more
severe neurologic manifestations (hemiplegia, subdural
effusion, and reversible acute encephalopathy) are only
described in published reports [1-6]. In one large series of
540 patients with Kawasaki disease, Terasawa and et al.
[1] described two infants with CNS involvement (0.4%).
Eight patients with acute encephalopathy associated with
Kawasaki disease were reviewed [1-3,5,6]. Their clinical
manifestations included disturbance of consciousness last-
ing between 2 and 11 days in all patients and status
epilepticus in two. Pleocytosis was observed in the CSF in
seven patients. The prognosis of neurologic complications
in Kawasaki disease is generally good. However, four
patients have been reported with sequelae, mainly moya-
moya disease (one patient), myoclonic seizures (one pa-
tient), and mild hemiparesis (two patients) [1,2,6]. These
severe forms of Kawasaki disease, like this patient, may
develop in patients having more severe and prolonged
inflammatory changes. The female patient was left with
severe sequelae despite early intravenous immunoglobulin
treatment. This raises the question of the optimal treatment
of the vasculitis of the nervous system in Kawasaki
disease; treatment could include another dose of immuno-
globulin, steroids, or other anti-inflammatory agents. Such
treatment should be considered for Kawasaki disease
patients who have failed to respond to intravenous immu-
noglobulin. Steroid treatment in Kawasaki disease has
been controversial. The treatment was first considered
unsafe because Kato et al. [8] reported that 65% of patients
who had received oral prednisolone alone for treatment of
Figure 1. T
1
-weighted MRI. In the acute period the MRI scan is normal
(A). Twelve months later a comparative slice reveals diffuse cerebral
atrophy (B).
Figure 2. T
1
-weighted MRI demonstrates diffuse cerebral atrophy.
240 PEDIATRIC NEUROLOGY Vol. 25 No. 3
acute Kawasaki disease developed coronary artery aneu-
rysms. Of note, none of the patients receiving oral pred-
nisolone and aspirin in combination developed coronary
artery aneurysms in that same study. More recently,
studies have found a beneficial role for steroids [9-12],
when used with aspirin, for initial treatment of acute
Kawasaki disease, and for the treatment of persistent or
recurrent fever after initial treatment with intravenous
immunoglobulin. Steroids appear to diminish the acute
inflammatory phase and prevent the progression of life-
threatening vascular complications. Further studies are
necessary, however, before such therapies can be recom-
mended routinely.
Kawasaki disease is characterized by systemic vasculi-
tis, mainly involving the coronary arteries. Such a patho-
logic mechanism could also affect the CNS and be
responsible for the neurologic symptoms. Although MRI
scans revealed no abnormalities at the acute stage of the
disease, the CNS manifestations associated with Kawasaki
disease might be due to focal impairment of blood flow
caused by cerebral vasculitis. In six of 21 children with
acute Kawasaki disease, single-photon emission computed
tomography (SPECT) imaging demonstrated localized
cerebral hypoperfusion without neurologic findings [13].
Postmortem examinations of children who have died of
Kawasaki disease provide some arguments in favor of
cerebrovascular involvement. Important findings in one
study included the following varying degrees of inflam-
matory changes in brain vasculature: leptomeningeal
thickening, mild endarteritis, and periarteritis [14].
Cardiac involvement is considered to be the most
important complication of Kawasaki disease. Coronary
artery aneurysms are found in 15-20% of untreated pa-
tients and tend to fall to approximately 5% among patients
who receive intravenous immunoglobulin therapy within
the first 10 days of illness [15]. Involvement of the CNS is
a rare, but sometimes serious, complication.
In conclusion, we would like to draw attention to the
fact that this disease, like many other vasculitic diseases,
can sometimes predominantly involve the CNS, which
exposes these patients to severe residual disabilities.
References
[1] Terasawa K, Ichinose E, Matsuishi T, Kato H. Neurological
complications in Kawasaki disease. Brain Dev 1983;5:371-4.
[2] Laxer RM, Dunn HG, Flodmark O. Acute hemiplegia in Ka-
wasaki disease and infantile polyarteritis nodosa. Dev Med Child Neurol
1984;26:814-8.
[3] Takagi K, Umezawa T, Saji T, Morooka K, Matsuo N. Menin-
goencephalitis in Kawasaki disease. No To Hattatsu 1990;22:429-35.
[4] Aoki N. Subdural effusion in the acute stage of Kawasaki
disease. Surg Neurol 1988;29:216-7.
[5] Sundel RP, Newburger JW, McGill T, et al. Sensorineural
hearing loss associated with Kawasaki disease. J Pediatr 1990;117:371-7.
[6] Shimura T, Toyama K, Shirai N, Nakashima T, Arima H. A case
of mucocutaneous lymph node syndrome with Moyamoya disease.
J Pediatr Pract 1976;39:1420-4.
[7] Dengler LD, Capparelli EV, Bastian JF, et al. Cerebrospinal fluid
profile in patients with acute Kawasaki disease. Pediatr Infect Dis J
1998;17:478-81.
[8] Kato H, Koike S, Yokoyama T. Kawasaki disease: Effect of
treatment on coronary artery involvement. Pediatrics 1979;63:175-9.
[9] Shinohara M, Sone K, Tomomasa T, Morikawa A. Corticoste-
roids in the treatment of the acute phase of Kawasaki disease. J Pediatr
1999;135:465-9.
[10] Dale RC, Saleem MA, Daw S, Dillon MJ. Treatment of severe
complicated Kawasaki disease with oral prednisolone and aspirin. J Pe-
diatr 2000;137:723-6.
[11] Han RK, Silverman ED, Newman A, McCrindle BW. Manage-
ment and outcome of persistent or recurrent fever after initial intravenous
gamma globulin therapy in acute Kawasaki disease. Arch Pediatr
Adolesc Med 2000;154:694-9.
[12] Wright DA, Newburger JW, Baker A, Sundel RP. Treatment of
immune globulin resistant Kawasaki disease with pulsed doses of
corticosteroids. J Pediatr 1996;128:146-9.
[13] Ichiyama T, Nishikawa M, Hayashi T, Koga M, Tashiro N,
Furukawa S. Cerebral hypoperfusion during acute Kawasaki disease.
Stroke 1998;29:1320-1.
[14] Amano S, Hazama F. Neural involvement in Kawasaki disease.
Acta Pathol Jpn 1980;30:365-73.
[15] Newburger JW, Takahashi M, Burns JC, et al. The treatment of
Kawasaki syndrome with intravenous gamma globulin. N Engl J Med
1986;315:341-7.
241Tabarki et al: Kawasaki Disease and Encephalopathy
