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Brain & Development 1994; 16:257-9

Case Report

Neonatal tuberous sclerosis presenting with intractable seizures
Paola Lago a, MD, Clementina Boniver b, MD, Gian Luca Casara b, MD,
Anna Maria Laverda b, MD, Angela Fiore a, MD, Sabrina Salvadori c, MD,
Carla Carollo d, MD, Onofrio Sergio Saia a, MD

A 2-day old girl with status epilepticus, unresponsive to maximum pharmacological intervention, is reported.
Findings of brain and cardiac lesions pointed to the diagnosis of tuberous sclerosis. One of the brain lesions was
unusually large, occupying most of the right temporo-parietal lobe.

Key words: Tuberous sclerosis, neonatal; Status epilepticus; Neonatal seizure, intractable; Cardiac rhabdomyom

1. INTRODUCTION
When diagnosed in the neonatal period, tuberous
sclerosis (TS) is characterized by either neonatal
seizures due to brain lesions or, more often, by signs of
congestive heart failure or arrhythmia due to accompanying cardiac rhabdomyomas [1].
This case report describes a newborn girl who presented unresponsive status epilepticus at the age of 2
days and was diagnosed as having TS by bedside ultrasonography showing multiple brain tubers and cardiac
tumors.

2. CASE REPORT
A female infant weighing 3,430 g was delivered after
39 weeks gestation to a healthy 30 year-old primigravida. Family history was unremarkable. The entire
course of pregnancy had been uneventful. The Apgar

Division of a Neonatology, b Neurology and c Cardiology, Department of Pediatrics, and d Department of Neuroradiology, University
of Padova, Padova, Italy
Received 28 September 1993; accepted 20 February 1994
Correspondence address: P. Lago, MD, Department of Pediatrics,
University of Padova School of Medicine, Division of Neonatology,
Via Giustiniani 3, 35128 Padova, Italy. Fax: (39) (49) 821 3502.

0387-7604/94/$07.00 © 1994 Elsevier Science B.V. All rights reserved
SSDI 0 3 8 7 - 7 6 0 4 ( 9 4 ) 0 0 0 3 0 - 2

scores were 8 at 1 min and 10 at 5 rain. At 2 days of
age she was admitted to our NICU with clonic jerks of
the mouth, chin, left arm and eyes, cardiac arrhythmia,
and hematuria. An abdominal mass was palpated and
there were no other remarkable findings on physical
examination. Brain ultrasound revealed two hypcrechogenic areas in the right parietal cortical and subcortical regions and in the left thalamus. At 5 days of age,
CT disclosed a large, high-density, round lesion, with
no contrast enhancement over the right temporoparietal lobe, while no abnormalities were evident in
the left hemisphere. MRI obtained at 3 weeks of age
showed a large area of hyperintense signal on T lweighted sequences, which was much more intense in
the subcortical region, with gyral anomaly and widening of the subarachnoid space. There was also evidence
of a second area of increased signal in the left corona
radiata, with extension to the basal ganglia (Fig. 1).
Both lesions showed a hypointense signal on T 2weighted image. A 2D echocardiogram showed two
hyperechogenic mass lesions confined to the free wall
of the left ventricle and to the muscular part of the
septum. These findings were compatible with cardiac
rhabdomyoma, causing dysrhythmia but no hemodynamic disturbance. Grade I atrioventricular block was
evident on EKG.
The findings of brain and cardiac lesions pointed to
a diagnosis of TS. No retinal, renal or liver involvement
was detected [1,2]. Hypomelanotic macules were not
found using ultraviolet light. A left adrenal hemorrage
was evident on renal ultrasound examination. During

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P. Lago et al. /Brain & Det'elopment 1994: 16:257 -t)

hospitalization, the child was hemodynamically stable,
and required no vasoactive drugs.
The clinical picture was dominated by intractable
seizures, which persisted despite treatment with various anti-epileptic drugs. Neurophysiological monitoring included repeated E E G tracings and continuous
cerebral function monitoring (CFM). During clinical
seizures E E G showed right Rolandic rhythmic discharge of sharp waves, spikes and complex waves,
while interictal tracings were characterized by multifocal abnormalities, more evident in the right hemisphere, and brief sequences of c~-like activity. The
CFM tracings showed the 'saw-tooth' pattern characteristic of repeated seizure activity.
The patient was first treated with phenobarbital 20
m g / k g loading dose, followed by 6 m g / k g once a day.
Despite a serum phenobarbital level above the therapeutic range (215 mmol/1) the seizures could not be
controlled. Several anti-epileptic drugs were tried: intravenous phenytoin (loading dose 18 m g / k g , followed
by 7 m g / k g t.i.d, until therapeutic range, 84 p, mol/1,
was obtained), repeated intravenous diazepam 0.5
m g / k g boluses, intravenous lidocaine (loading dose 2
m g / k g , followed by 6 m g / k g / h infusion), valproic acid
(60 m g / k g t.i.d.) and vigabatrin 100 m g / k g t.i.d, per
os. Barbiturate coma (BC) induced with pentobarbital
sodium 3 m g / k g bolus i.v. as a loading dose, followed
by 5 - 9 m g / k g / h drip infusion was attempted at 2

weeks of age, resulting in partial control of the electrical discharges in the brain. Attempts to wean the
infant from the BC after 5 days, 1 week and 2 weeks
failed, as critical activity reappeared as soon as the
infusion rate of pentobarbital sodium was reduced.
The child died of cardiorespiratory arrest at 1 month
of age. The postmortem examination confirmed the
presence of cerebral tubers, cardiac rhabdomyomas
and adrenal hemorrhage.

3. DISCUSSION
Tuberous sclerosis is a neurocutaneous syndrome
transmitted through a dominant gene, with variable
expression and penetrance. A high incidence (50%) of
new mutations is reported [1-3]. In this case, the
genetic work-up performed in the parents and their
siblings was negative, suggesting a new genetic mutation.
In neonatal TS, multiple cardiac rhabdomyomas are
classically present and a spontaneous involution of
these tumors has quite often been observed at an early
age [4].
Macroscopic hematuria associated with adrenal
hemorrage has occasionally been reported in newborn
infants [5]. Renal function was always normal in our
patient, and hematuria, possibly due to compression of

Fig. 1. MRI T l-weighted image, on coronal (a) and axial (b) view: a large area of increased signal is more evident in the deep white matter of the
right temporo-parietal region, with gyral anomaly and widening of the subarachnoid space. Another small area of increased signal is evident in
the paraventricular left parietal region.

P. Lago et al. /Brain & Development 1994; 16:257-9

the renal vein (pseudothrombosis), recovered within a
few days.
The clinical presentation of TS in the newborn is
very variable [6-8]. At the onset the most frequent
symptoms are cardiac arrhythmia or heart failure, due
to rhabdomyoma, while seizures are seen later. This
case was unusual because it was dominated by a precocious status epilepticus which proved very difficult to
control with drugs; a surgical approach was not considered because of the extension of the lesions.

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