Fortuitous diagnosis of a giant thoracoabdominal aneurysm in a patient with tuberous sclerosis compl

1

• Fortuitous diagnosis of a giant thoraco-abdominal
  aneurysm in a patient with tuberous sclerosis
  complex

Ulrike Mietzsch, MD Fellow in Neonatal-Perinatal
Medicine University of Texas Health Science
Center at Houston, Medical School Department of
Pediatrics, Division of Neonatology
2
Abstract

• We report the case of a 3 year-old male with
  tuberous sclerosis complex who presented with an
  incidental finding of a giant thoraco-abdominal
  aneurysm with recurrence after 10 months, and
  review of the literature.
• Aortic aneurysms in children are rare but always
  fatal if untreated.
• Conclusion
• We recommend that echocardiography be included
  in the clinical follow up of patients with
  tuberous sclerosis complex.

3
Introduction - Tuberous Sclerosis

• TSC was first described in 1862 by von
  Recklinghausen (German Pathologist).
• TSC was named by Bourneville (French Neurologist)
  in 1880.
• It is a rare genetic disease that affects 16,000
  live births.
• 50,000 patients in the US, and gt1,000,000
  patients worldwide are affected.
• Tuberous sclerosis complex (TSC) is an autosomal
  dominant disease.
• TSC1 mutation of Hamartin, occur within the
  same family
• TSC2 mutation of Tuberin, most common
  spontaneous mutations

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Introduction Tuberous Sclerosis

• TSC can affect virtually any part of the body
  with highly variable clinical manifestations,
  even among related patients.
• Although many patients are undiagnosed due to the
  obscurity of the disease, most present during
  childhood with neurological symptoms or
  developmental abnormalities.
• Tumors in the skin, kidneys, brain, heart, as
  well as other organ systems are common physical
  findings.

Désiré-Magloire_Bourneville (1840-1909)
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Diagnostic criterias of TSC

• Major features
• Facial angiofibromas or forehead plaque
• Non-traumatic ungual or periungual fibroma
• Hypomelanotic maculae (three or more)
• Shagreen patch (connective-tissue nevus)
• Multiple retinal nodular hamartomas
• Cortical tubers
• Subependymal nodule
• Subependymal giant-cell astrocytoma
• Cardiac rhabdomyoma, single or multiple
• Lymphangiomyomatosis
• Renal angiomyolipoma

• Minor features
• Multiple, randomly distributed pits in dental
  enamel
• Hamartomatous rectal polyps
• Bone cysts
• Cerebral white matter radial migration lines
• Gingival fibromas
• Non-renal hamartoma
• Retinal achromic patch
• 'Confetti' skin lesions
• Multiple renal cysts

6
Case Presentation History of Present Illness

• A 3-year-old boy, known to have TSC, was found
  to have a new, non-tender, mobile subcutaneous
  mass in the right upper abdominal quadrant.
• An ultrasound performed to evaluate this
  revealed a massive aortic abdominal aneurysm,
  prompting a referral to our Institution.

7
Case Presentation Past Medical History

• The child was diagnosed with tuberous sclerosis
  complex (TSC2) at 5 months of age when he
  presented with generalized tonic-clonic seizures,
  neurofibromas in the subcutaneous lumbar area,
  and multiple hypopigmented maculae.
• CT of the brain at that time showed multiple
  subependymal lesions, and tumors in the left
  parietal and frontal lobes.
• MRI of the brain showed multiple subependymal
  nodules and multifocal white matter dysplasia

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Case Presentation Physical Exam

• Cutaneous findings
• Multiple hypopigmented maculae on his forehead,
  chin and lower trunk
• Small facial angiofibromas in his cheeks
• Small Shagreen patch in the thoraco-lumbar region
• Small subcutaneous, mobile, non-tender mass
  palpable in the right upper abdominal quadrant

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Case Presentation Physical Exam

• He was non-dysmorphic, well nourished and in no
  acute distress.
• His growth parameters and vital signs were within
  normal limits for age.
• The systolic blood pressure was mildly elevated
  at 106 mmHg during sleep (95th percentile for his
  height and age).
• His motor milestones were normal, but he did
  exhibit some developmental speech delay.
• The remainder of the physical exam was normal.

10
Case Presentation

• All laboratory parameters such as
• Serum electrolytes
• Coagulation panel
• Complete blood cell count
• C-reactive protein
• Thyroid function tests
• Liver enzymes
• were within normal range for his age.

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Echocardiography

• Four chambered anatomy with normally related
  great arteries, and no intracardiac echodensity
  consistent with rhabdomyoma were seen.
• The ascending aorta and the transverse aortic
  arch were unremarkable.

12
Echocardiography

• The distal thoracic and the proximal abdominal
  aorta, just below the diaphragm, exhibited
  multiple areas of irregular fusiform dilation.

13
Echocardiography

• There was an irregular echodensity in the
  proximal area of the aneurysm, suggestive of an
  intra-aneurismal thrombus.

14
Cardiac MRI

• A magnetic resonance angiogram of the thoracic
  and abdominal aorta confirmed the presence of a
  complex thoraco-abdominal aneurysm with three
  discrete fusiform dilations.
• The distal thoracic aorta harbored the first and
  most proximal aneurismal dilation, measuring 2.8
  cm in length and 2.4 cm at its greatest diameter.
  
• The second fusiform dilation, located in the
  proximal abdominal aorta, was 5.3 cm in length,
  and from which the celiac artery arose.
• The third fusiform dilation involved the origins
  of the superior mesenteric artery and both renal
  arteries.

1st
2nd
3rd
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Clinical Course

• Upon admission, the patient was started on
  atenolol to decrease the blood pressure and
  minimize the risk of spontaneous rupture of the
  aneurysm.
• The patient underwent surgical resection and
  graft replacement of the thoraco-abdominal
  aneurysm with a 16 mm Gelweaved woven Dacron tube
  graft, with reinsertion of the celiac, superior
  mesenteric and renal arteries.

16
Surgical Pathology

• Cystic media necrosis, loss of smooth muscle
  from the muscular media, fibrous proliferation

17
Clinical Course

• The patient had an uneventful recovery and was
  discharged home 5 days after the surgery.
• On the patients six week follow-up visit, he was
  doing well.
• A CT scan of the chest and abdomen revealed an
  intact thoraco-abdominal graft with normal
  perfusion of the viscera.

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Clinical Course

• On his follow-up visit 10 months after the
  initial repair, he was clinically asymptomatic on
  atenolol.
• The CT angiogram showed reformation of the
  thoracic part of the aneurysm, the largest
  transverse diameter measuring 6.5 cm.

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Clinical Course

• He was re-admitted for surgical repair of the
  recurrent aneurysm.
• Intraoperatively, tuber formation at the site of
  the proximal anastomosis was noted.
• The histology was identical with the previous
  specimen, except for increased loss of smooth
  muscle cells in the muscular media.
• A second 16 mm Gelweaved woven Dacron tube graft
  was placed proximal to the previous graft. He
  tolerated the procedure well and was discharged
  on postoperative day 5.
• Twelve months after the second repair, no
  reformation of the aneurysm is noted. He remains
  stable on atenolol

20
Discussion

• An unusual and less recognized complication of
  TSC is the development of vascular abnormalities
  including aortic aneurysms (14).
• Although there have been previous case reports of
  aortic aneurysms occurring in children with TSC,
  recommendations regarding the management and
  follow up of such patients have not been
  established (4,8,9).

21
Discussion

• Neurologic and psychiatric symptoms of TSC cause
  the most significant patient morbidity.
• Although rhabdomyomas are the most common cardiac
  lesions, these tend to regress spontaneously and
  are symptomatic only when they result in cardiac
  obstruction or cause significant arrhythmias.

22
Discussion

• Fortunately, the development of aortic aneurysms
  is rare.
• However, cardiovascular accidents related to
  their rupture are the leading cause of death
  (50) in children with cardiovascular
  manifestations of TSC (16).

23
Aortic Aneurysms in Childhood

• Aortic aneurysm in childhood are rare
• Most common cause posttraumatic
• Other
• Secondary to infections especially fungal
  infections
• Vasculitis syndromes
• Kawasaki Syndrome
• Henoch-Schoenlein purpura
• Takayasu Arteritis
• Connective tissue diseases
• Marfan Syndrome
• Ehlers-Danlos Syndrome
• Tuberous sclerosis

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Mechanism of Aneurysm Formation

• The mechanism of aneurysm formation in TSC is not
  fully understood
• Theories proposed in the literature
• Chronic inflammation and hamartoma formation lead
  to ischemia of the vasa vasorum. This results in
  the loss of media integrity and the subsequent
  development of tissue necrosis that eventually
  leads to fibrous tissue formation (7).
• Towbin et al. suggest that hamartoma formation
  may result in widespread arterial dysplasia,
  predisposing the patient to progressive
  degenerative changes in large elastic vessels
  (18).
• Although extensive degenerative changes were seen
  in our patients specimen, no hamartoma formation
  was seen in the initial aortic wall specimen.
  However, macroscopic inspection of the reformed
  aneurysm was suggestive for tuber formation at
  the site of anastomosis.

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Mechanisms of Aneurysm Formation

• Theories proposed in the literature continues
• Another theory suggests that hypertension, a
  common feature in aneurysm formation in adult
  patients, is the cause of aortic dilatation in
  TSC (12).
• It was postulated that patients with TSC may
  develop renal artery hamartomas, which may result
  in hypertension and eventual aneurysm formation.
• Alternatively, aortic aneurysms affecting the
  renal arteries may result in renal artery
  stenosis leading to hypertension (20).
• This may be a less plausible theory in our case,
  as the relative size of the aortic aneurysm in
  our young patient seems disproportionate to the
  relatively shorter time that he may have been
  exposed to prolonged periods of hypertension.

26
Conclusion

• Other case reports indicate that intimal
  hyperplasia and media fibrosis with degeneration
  as the potential endpoint is a common finding in
  TSC patients developing aneurysms (4,8,9).
• As our patient exhibited similar histological
  findings, we postulate that there must be a close
  association between aneurysm formation and
  fibromuscular dysplasia.
• We thus agree with Beltramello et al. that
  aneurysm formation might be explained by the
  association of TSC and vascular dysplasia (3).

27
Conclusion

• As more and more cases are reported in the
  literature (see table 1), it is increasingly
  evident that vascular aneurysm formation might
  not be as rare as previously thought.
• All previous case reports show the same
  histological features of degenerative fibrosis.
• This form of vascular abnormalities may indeed be
  part of the TSC.

28
Review of Literature Table 1
29
Conclusion

• Many patients with TSC come to the attention of
  pediatric cardiologists even before birth, when
  they present with fetal arrhythmias and cardiac
  tumors.
• As many of these findings spontaneously improve,
  a significant proportion of these patients are
  lost to cardiology follow-up.
• As our case and the many others illustrate, this
  may not be in the patients best interest, as
  aneurysm formation may occur at any time during
  childhood.
• Though rare, they are uniformly fatal if not
  recognized and treated early in the course.
  Patients without cardiac involvement at birth or
  at diagnosis of TSC are not routinely followed up
  for cardiovascular complications until they
  become symptomatic.

30
Recommendation

• Although current guidelines do not support this
  (14), we thus recommend routine pediatric
  cardiology follow-up of all patients with TSC,
  which should, at the very least, include an
  annual echocardiogram.

31
Thank you!

• G. Biliciler-Denktas, MD
• Assistant Professor, UT HSC at Houston
• Department of Pediatrics
• Division of Pediatric Cardiology
• R. Lantin-Hermoso, MD
• H. Safi, MD
• A. Estrella, MD
• M. Covinsky, MD
• L. Kramer, MD
• S. Lopez, MD

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