British Journal of Anaesthesia 1994; 73: 421-425
Anaesthesia and tuberous sclerosis
J. J. LEE, M. IMRIE AND V. TAYLOR
Summary
The anaesthetic management of a patient with
tuberous sclerosis undergoing two-stage scoliosis
surgery is described. The patient suffered from
severe mental retardation, seizures and facial angio-
fibromas. General anaesthesia using isoflurane and
nitrous oxide in oxygen, supplemented with opioid
analgesia and hydralazine, and labetalol to induce
hypotension, appeared to be satisfactory. Post-
operative recovery was delayed and complicated by
pieural effusion, sputum retention and mild seizures.
Tuberous sclerosis is an autosomal dominant dis-
ease well known for its neurocutaneous mani-
festations. Other organs such as the heart, lungs
and kidneys may be involved. The potential
problems in the anaesthetic management of a
patient with tuberous sclerosis are discussed. (Br.
J. Anaesth. 1994; 73: 421-425)
Key w o r d s
Surgery, orthopaedic. Complications, tuberous sclerosis.
Tuberous sclerosis (synonym: Bourneville's disease)
is an autosomal dominant disease, best known for its
cutaneous and neurological manifestations and de-
scribed classically as a characteristic triad of mental
retardation, seizures and facial angiofibroma [1].
Very little information is available in anaesthetic
textbooks on tuberous sclerosis. We are also unaware
of any previous report of anaesthetic experience with
tuberous sclerosis, except three case reports in non-
English journals [2-4]. We discuss the anaesthetic
management of a patient with tuberous sclerosis.
Case report
A 13-yr-old, 33-kg white female with tuberous
sclerosis, which was diagnosed at 2 yr of age, was
scheduled for a two-stage surgical correction of a
scoliosis curve of 76° (denned by the Cobb method),
for relief of pulmonary problems and to make
nursing and wheelchair management easier. She
developed progressive right-sided scoliosis (from
T7-L3) with the onset of puberty at age 10 yr. She
was severely mentally and physically handicapped,
partially blind, doubly incontinent and had "a
tendency to scream when she was unhappy". She
also suffered from recurrent chest infections and
frequent grand mal and petit mal seizures. Her
regular medications included sodium valproate
300 mg three times daily, carbamazepine 200 mg
three times daily and nitrazepam 10 mg at night.
There was no history of drug allergy or previous
anaesthesia.
On examination she looked calm but became
apprehensive and restless during physical exam-
ination. She has marked facial angiofibroma over the
cheeks and nose. She preferred to keep her elbows,
hips and knees flexed, but there were no evidence of
flexure contractures of the limbs and she was able to
grip objects for a few seconds before dropping them.
There was no obvious muscle wasting but muscle
tone and reflexes in all limbs were reduced. Exam-
ination of the respiratory and cardiovascular systems
was unremarkable. Preoperative investigations re-
vealed a haemoglobin concentration of 10.1 g dl"1,
and serum electrolyte, urea and creatinine con-
centrations were normal. Chest x-ray, electro-
cardiography (ECG) and ultrasonography of both
kidneys were normal. A previous echocardiogram
performed 12 months earlier revealed no abnor-
mality. Lung function tests could not be performed.
Antiepileptic therapy was continued up to the time
of premedication when she was given temazepam
20 mg orally and EMLA cream topically to both
hands.
FIRST STAGE—ANTERIOR RELEASE
The child appeared adequately sedated on arrival in
the anaesthetic room. Monitoring was commenced
before induction of anaesthesia with thiopentone
250 mg i.v. Vecuronium 7 mg was given to facilitate
tracheal intubation and ventilation, and anaesthesia
maintained with isoflurane and nitrous oxide in
oxygen. Intraoperative monitoring included ECG,
intra-arterial pressure, central venous pressure
(CVP), pulse oximetry, end-tidal carbon dioxide and
inspired oxygen concentration, and nasopharyngeal
temperature. A nasogastric tube was inserted but
urinary catheterization was avoided because of the
increased risk of infection. Hydralazine 5 mg and
labetalol 40 mg were administered to maintain
systolic pressure at 80-90 mm Hg throughout the
operation. CVP was maintained at 12-14 cm H2O. A
total dose of 7 mg of morphine was given for
intraoperative analgesia.
J. J. LEE*, FFARCSI, M. IMRIET> FRCA, V. TAYLOR, FRCA, Depart-
ment of Anaesthesia, Royal National Orthopaedic Hospital,
Stanmore, Middlesex, HA7 4LP. Accepted for publication:
March 10, 1994.
Present addresses:
•Department of Anaesthesia, Royal London Hospital,
Whitechapel, London El IBB.
t Department of Anaesthesia, St Peter's Hospital, Guildford
Road, Chertsey, Surrey KT16 0PZ.
422
The patient was placed in the left lateral position.
Anterior release and fusion were performed through
a right thoracoabdominal incision and in which five
discs and vertebral end-plates were removed from
the apex of the curvature. The lowest intraoperative
temperature was 34.6 °C. The measured blood loss
of approximately 420 ml was replaced with 1 litre of
crystalloid and 1 u. of blood. A right chest drain was
inserted towards the end of operation which lasted
3 h. After tracheal extubation she was admitted to
the high dependency unit (HDU) for routine
postoperative management [5].
During her stay in the HDU, heart rate, arterial
pressure and ventilatory frequency were monitored
regularly and oxygenation was monitored with
continuous pulse oximetry (.Sp02). Throughout this
period postoperative pain relief was managed suc-
cessfully using continuous i.v. infusion of morphine
2 mg h"1. She appeared pain-free by her calm
behaviour even during physiotherapy and at no time
was she oversedated. On the first day after operation,
her antiepileptic drugs were resumed and ad-
ministered via the nasogastric tube when bowel
sounds were heard. Haemoglobin concentration was
10.6 g dl~' and biochemistry was normal. A Bird
ventilator was used at regular intervals for patient-
triggered positive pressure ventilation as part of
chest physiotherapy with which she co-operated
well. However, on the second day after operation,
she was pyrexial and retaining sputum with poor
arterial oxygenation (Po2 = 9.0 kPa) whilst breathing
40% oxygen. Auscultation revealed reduced air
entry in the left lung field. Cefuroxime was started
after sputum culture which was subsequently nega-
tive. Chest x-ray revealed a "white-out" of the left
lung field which was consistent with pleural effusion.
The right lung with the chest drain in situ was clear.
She responded well to treatment with 60 % oxygen,
CPAP 5 cm H2O and insertion of a left chest drain
which drained 400 ml of blood-stained sero-
sanguinous fluid. She continued to recover until day
5 when SpOi decreased from 95 % to 80 % whilst
breathing 35 % oxygen, again because of sputum
retention, but recovered rapidly after chest physio-
therapy. Two days later, chest x-ray revealed only a
small residual left-sided pleural effusion and there
was minimal chest drainage and no air leak. Both
chest drains were thus removed and she returned to
the ward.
SECOND STAGE—POSTERIOR FUSION
Two weeks after the first stage, the patient was
scheduled for the second stage correction of scoliosis
which involved posterior fusion and instrumentation
using Harrington rod and Luque sublaminar wires.
She received a similar general anaesthetic and was
placed prone on a Montreal mattress during surgery.
Intraoperative spinal cord monitoring was com-
menced after the surgeons had placed the recording
electrodes in the extradural space through the
surgical wound. The operation lasted 3 h; measured
blood loss was approximately 1000 ml which was
replaced and the lowest intraoperative temperature
was 34.5 °C.
British Journal of Anaesthesia
Her recovery in the HDU was uneventful and she
returned to the ward on day 3 after operation. She
suffered two episodes of mild but transient and
uncomplicated epileptic fits on the ward. However,
she was discharged home 10 days later after being
fitted with a plaster jacket. She remained well when
she was reviewed in the outpatient clinic 3 months
later.
Discussion
Various types of surgery performed in patients with
tuberous sclerosis have been described. The majority
of these were indicated for pathologies associated
with tuberous sclerosis and included tumour re-
section or nephrectomy for renal angiomyolipomas
[6], cortical resection and stereotaxic lesionectomy
for medically intractable seizures [7], laser treatment
of angiofibroma [8] and cardiac surgery for patients
with refractory arrhythmias or severe haemodynamic
compromise as a result of cardiac rhabdomyomas [9].
However, anaesthetic experience and management of
tuberous sclerosis have never been reported in
English language journals or described in standard
anaesthetic textbooks. We are aware of only three
published reports of anaesthetic experience in a total
of four patients with tuberous sclerosis in non-
English language medical journals [2-4]. All the
general anaesthetics were uneventful except for a
case of sinus bradycardia which occurred in a 4-yr-
old boy during postoperative recovery from an-
aesthesia. The arrhythmia responded to atropine
0.2 mg [2]. In our patient, general anaesthesia using
isoflurane and nitrous oxide in oxygen, supple-
mented with opioid analgesia and hydralazine and
labetalol to induce hypotension, appeared to be sat-
isfactory for scoliosis surgery in tuberous sclerosis.
Our patient co-operated reasonably well with the
routine postoperative management of scoliosis sur-
gery in the HDU and the use of continuous i.v.
infusion of morphine for postoperative analgesia was
satisfactory. Continuous extradural analgesia is also
a useful alternative technique for the first stage
correction despite greater difficulty with such a
procedure owing to the scoliosis. However, her first
stage recovery was complicated by pleural effusion
and sputum retention. This "sympathetic" pleural
effusion is a recognized complication of the first stage
anterior release [10, 11]. The occurrence of sputum
retention may be attributable to her mental re-
tardation and the use of continuous morphine
infusion causing drowsiness may be avoided by
using continuous extradural analgesia and more
aggressive physiotherapy. Finally, she did not suffer
any of the complications of posterior spinal fusion
reported previously [5], except for mild seizures
which were associated with tuberous sclerosis.
Gomez has published an authoritative and detailed
monograph on tuberous sclerosis [1]. The various
clinical manifestations of tuberous sclerosis which
have potential implications in the anaesthetic man-
agement of a patient with tuberous sclerosis are
reviewed and summarized.
In 1880 Bourneville presented the first detailed
report of the neurological symptoms and cerebral
Anaesthesia and tuberous sclerosis 423

Table 1 Diagnostic criteria for tuberous sclerosis (TS) (summarized from Roach and colleagues [13]). Definite
TS = either one primary, two secondary or one secondary plus two tertiary features; probable TS = either one
secondary plus one tertiary or three tertiary features; suspect TS = either one secondary or two tertiary features
I. Primary features
Facial angiofibromas
Multiple ungual fibromas
Cortical tuber (histology)
Subependymal nodule or giant cell astrocytoma (histology)
Multiple calcined subependymal nodules protruding into ventricle (radiology)
Multiple retinal astrocytomas
II. Secondary features
Affected first-degree relative
Cardiac rhabdomyoma
Other retinal hamartoma or achromic patch
Cerebral tubers (radiology)
Non-calcified subependymal nodules
Shagreen patch
Forehead plaque
Pulmonary lymphangiomyomatosis (histology)
Renal angiomyolipoma
Renal cysts (histology)
III. Tertiary features
Hypomelanotic macules
"Confetti" skin lesions
Renal cysts (radiography)
Randomly distributed enamel pits in deciduous and/or permanent teeth
Hamartomatous rectal polyps
Bone cysts
Pulmonary lymphangiomyomatosis (radiology)
Cerebral white matter "migration tracts" or heterotopias
Gingival fibromas
Hamartoma of other organs
Infantile spasms

pathology of tuberous sclerosis and gave the de-

scription, "tuberous sclerosis of the cerebral convo-
lutions" [1]. Tuberous sclerosis is a genetic disorder
with an overall prevalence of about 1 in 29000; 1 in
15000 for those less than 5 yr of age and a birth
incidence as high as 1 in 10000, making it one of the
most common autosomal dominant disorders [12].
New mutation cases have also been recognized. It is
renowned for its variable genetic expression and thus
extremely variable clinical manifestations among
patients. There is presently no specific genetic
molecular marker and so clinical diagnostic criteria
have to be relied upon. Various attempts have been
made to draw up diagnostic criteria over the years,
but recently a consensus report of the Diagnostic
Criteria Committee of the National Tuberous Scler-
osis Association has been published (table 1) [13].
However, while it is easy to provide a definitive
diagnosis of tuberous sclerosis when many clinical
features of the criteria are present, tuberous sclerosis
cannot be excluded when only a few physical or
radiological signs are present in atypical or subtle
forms. No single feature is invariably present. Hence,
the classic triad (Vogt's) of mental retardation,
seizures and facial angiofibroma is present in only
about 30 % of patients with tuberous sclerosis and
about 6% have none of the triad. Pathologically,
tuberous sclerosis can be described as a condition
where a constellation of benign hamartomatous
proliferative lesions and malformations (hamartias)
occur in virtually every organ or part of the body and
therefore possibly a disorder of cell migration,
proliferation and differentiation [14]. Features of
tuberous sclerosis relevant to anaesthetic manage-
ment are discussed.
CENTRAL NERVOUS SYSTEM
Mental retardation (approximately 60 % of tuberous
sclerosis patients) and epileptic seizures (80-90%)
are the most common neurological problems in
tuberous sclerosis [15]. They have been described as
part of the classic triad, but are now no longer
included as diagnostic features (table 1) because they
are also ubiquitous in the general population and
play no specific role in the diagnosis of tuberous
sclerosis. However, infantile spasms, which are
particularly common, are regarded as a tertiary
feature. Hyperactive and autistic behaviour are also
common. Nevertheless, a tuberous sclerosis patient
with a history of seizures may not be controlled
adequately and may be receiving multiple anti-
epileptic therapy with the risk of drug interactions.
Antiepileptic drugs should not be discontinued
before operation. Propofol and enflurane should be
avoided. Adequate postoperative pain relief is vital
and also early resumption of antiepileptic therapy.
Some drugs, such as carbamazepine, cannot be given
parenterally, thus alternative and equally effective
antiepileptic drugs should be used without delay if
gastrointestinal absorption becomes unreliable be-
cause of postoperative ileus.
Brain lesions resulting from tuberous sclerosis,
include cortical tubers, subependymal nodules and
giant cell astrocytoma. Cortical tubers, for which
tuberous sclerosis is named, average 1-2 cm in
diameter and vary in number from none to several
dozen. Subependymal nodules, typically found in
lateral ventricles, tend to become calcified and visible
on x-rays, and may enlarge to cause symptoms.
Giant cell astrocytomas may also enlarge and present
424
with new focal neurological deficits, raised intra-
cranial pressure, behavioural changes or loss of
seizure control, and also obstruction of the ven-
tricular system and haemorrhage within the tumour
and surgical interventions may be required. Despite
the use of magnetic resonance imaging (MRI),
currently the most sensitive method for localizing
cortical tubers, questions regarding the complex
relations between cerebral lesions, seizures and
mental aspects remain unresolved. However, cer-
ebral MRI may be of great prognostic value in newly
diagnosed cases [16].
Electroencephalographic recordings (EEG) in
patients with tuberous sclerosis [1] did not reveal a
specific type of pattern but a diversity of abnor-
malities which indicate focal or multifocal cerebral
disorder and relate more to the age at onset, type of
seizure, severity of mental retardation and disease
progress. It provides a good indicator of the severity
of cerebral dysfunction.
CARDIOVASCULAR SYSTEM
Cardiac rhabdomyoma is rare but is the commonest
benign primary cardiac tumour found in young
children and is frequently (up to 46.7%) associated
with tuberous sclerosis [17]. Single or multiple
rhabdomyomas may occur in any cardiac chamber
but more frequently in the ventricles and left side of
the heart. Cardiac signs and symptoms are caused by
obstruction of blood flow through the heart (intra-
cavitary tumours) or myocardial involvement and
arrhythmias (intramural tumours), including atrial
and ventricular tachycardias, complete heart block
and ventricular fibrillation, which may all result in
severe congestive cardiac failure. Recently the as-
sociation of Wolff-Parkinson-White syndrome in
tuberous sclerosis with and without cardiac rhab-
domyoma has also been reported [1, 18]. Echo-
cardiography and, more recently, MRI [19], are
extremely important non-invasive investigations to
allow identification of both intracavitary and intra-
mural tumours, and it has been recommended that
all patients with tuberous sclerosis should have such
screening periodically. Obstructive intracavitary
tumours require surgical removal and cardiac failure
and arrhythmias should be treated accordingly.
Involvement of the medium-sized arteries of the
kidneys, lungs, liver and adrenal glands has been
reported. The renal medium-sized arteries may
reveal medial layer thickening, deficient elastic tissue
and narrowed lumen. Rarely, thoracic and abdominal
aortic aneurysms and intracerebral aneurysms have
been reported in very young infants [18].
RESPIRATORY SYSTEM
Lung involvement is rare ( < 1 % ) in tuberous
sclerosis, with symptoms and radiological abnor-
malities occurring late and almost confined to women
in the third or fourth decade. The clinical, radio-
logical and pathological features are similar to those
of pulmonary lymphangiomyomatosis with cystic
changes. Patients usually present with severe and
progressive dyspnoea, spontaneous pneumothorax
which may be recurrent, haemoptysis and respiratory
British Journal of Anaesthesia
failure. Lung function tests show an obstructive
pattern and hypoxaemia is evident on arterial
blood-gas analysis. Chest x-ray may reveal a cystic
or honeycomb appearance of the lung parenchyma,
which may be localized or widespread. The pul-
monary lesions have a poor prognosis when
symptoms begin and are the cause of death in the
majority of fatal cases of tuberous sclerosis. How-
ever, progesterone therapy, oophorectomy, or both,
have been shown to improve or stabilize the
pulmonary lesion in the majority of cases [18].
RENAL SYSTEM
Renal involvement in tuberous sclerosis in the form
of angiomyolipomas and cysts was the most common
cause of death in one series [20]. Renal angio-
myolipomas, which occur in 50% to 80% of
tuberous sclerosis patients [15], are tumours with
highly vascular growth of smooth muscle and adipose
tissue, and are more common than renal cysts. The
simultaneous occurrence of angiomyolipomas and
cysts is characteristic of tuberous sclerosis and both
are typically multiple and bilateral, innocuous and
silent.
Renal angiomyolipomas are seldom troublesome
to the patient. Symptoms may be chronic, vague,
evanescent or dramatic, consisting of poorly local-
ized, intermittent abdominal, lumbar or flank pain
which may be associated with nausea, vomiting and
abdominal distension. Gross haematuria and acute
flank pain may result from haemorrhage into the
tumour. Rarely, renal failure and massive retro-
peritoneal haemorrhage have been reported.
Renal failure as a result of renal cysts may be an
initial presenting feature of tuberous sclerosis in
children [21]. Renal cysts have an earlier onset than
angiomyolipomas, can be few and asymptomatic or
numerous and macroscopically similar to adult
polycystic kidney disease. Other associated features
include hypertension, haematuria, flank pain, pal-
pable renal masses and proteinuria. Ultrasonography
remains the most sensitive method of detecting these
renal abnormalities and computerized tomography
the most specific method of confirming their identity.
Patients with tuberous sclerosis may have an in-
creased risk of renal cell carcinoma, of which several
cases have been reported.
ENDOCRINE SYSTEM
Tuberous sclerosis may rarely be associated with
endocrine abnormalities of which the adrenal glands
are most frequently affected. The most common
adrenal abnormality is angiomyolipoma. Other en-
docrine abnormalities reported include adreno-
genital syndrome, thyroid adenoma and dysfunction,
hypothalamic and pituitary dysfunction, angiomyo-
lipomas and fibroadenomas of the testes and hyper-
parathyroidism [1].
MOUTH, PHARYNX AND LARYNX
Oral lesions such as nodular tumours, fibromas or
papillomas have been described in patients with
tuberous sclerosis (11 %) and found on the tongue,
Anaesthesia and tuberous sclerosis
palate and less frequently on the pharynx and larynx,
all of which may interfere with anaesthetic airway
management [1].
The causes of death in tuberous sclerosis were
reported by the Mayo Clinic, after reviewing 355
patients with tuberous sclerosis, of whom 40 died of
the condition [20]. A 3-day-old baby died of cardiac
failure because of cardiac rhabdomyomas and a 3-yr-
old girl from rupture of a thoracic aortic aneurysm.
Eleven patients died of renal involvement, all were
aged 10 yr or older, and the frequency of death
increased with advancing age. Ten died from brain
tumours and this occurred most frequently between
10 and 19 yr of age. Four patients who were 40 yr or
older died from pulmonary lymphangiomyomatosis.
In the remaining 13 patients with severe mental
retardation as a result of tuberous sclerosis, the cause
of death was status epilepticus in nine and bron-
chopneumonia in four patients. Study of survival
curves revealed a decreased life expectancy among
patients with tuberous sclerosis compared with the
general population. Hence, the overall prognosis of a
patient with tuberous sclerosis depends on which
organ or organs are involved and the extent of organ
involvement, ranging from no symptoms to those
causing severe symptoms, disability and even death.
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