CHLA Case Presentation

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CHLA Case Presentation
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History

• HPI 10 year old male with Down syndrome and a 1
  week history of headache, nausea, vomiting,
  dizziness and unsteady gait.
• PMH Down syndrome, ASD
• PSH PE tubes, orchiopexy
• Meds None
• NKDA

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Physical Exam

• Awake and alert
• CN II-XII intact
• Motor 5/5 bilaterally
• Sensation Intact bilaterally
• Reflexes Symetric, no Babinski
• CBLM FTN and RAM intact, gait ataxic

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Differential Diagnosis

• Cavernous malformation
• Teratoma

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Procedure

• Posterior fossa craniotomy with gross total
  resection of mass

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Diagnosis

• Cavernous Malformation

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Cavernous Malformation

• Also known as cavernous angiomas, cavernomas and
  hemangiomas
• Gross appearance is red and lobulated, similar to
  mulberries
• Size is usually 0.5 to 3 cm
• Adjacent brain is often hemosiderin stained

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Cavernous Malformation

• No large supplying artery or draining vein
• Low flow
• No intervening brain
• Adjacent brain not ischemic
• Microscopically have blood containing sinusoidal
  chambers lined by simple epithelium
• The vascular spaces are separated by fibrous or
  collagenous tissue rather than brain
• Often have a gliotic margin

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Cavernous Malformation

• 9 of all types of brain vascular malformations
• Prevalence is 0.4-0.8
• MF ratio is11
• Age at presentation 20-40
• Present with headache, focal neurological
  deficit, seizures, hemorrhage

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Cavernous Malformation

• CM can repetitively hemorrhage resulting in
• Gliosis
• Tissue discoloration
• Hemosiderin-laden macrophages
• Microcalcification
• Hyalinization
• Cysts with blood breakdown products

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Cavernous Malformation

• Can be familial
• Hispanic families
• CCM1, 7q11-21
• Non-Hispanic families
• CCM2, 7p13-15
• CCM3, 3q25.2-27

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Risk of hemorrhage

• Cantu, C., L. Murillo-Bonilla, et al. (2005).
  "Predictive factors for intracerebral hemorrhage
  in patients with cavernous angiomas." Neurol Res
  27(3) 314-8.
• 133 Hispanic patients with 5 year follow-up
• ICH rate 1.71 per patient per year
• Lobar 1.22
• Brainstem 2.33
• Cerebellum 2.39
• Deep hemispheric 2.82
• Decreased rate of hemorrhage if family history of
  epilepsy or lobar location of CM

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Association with Venous Malformations

• Abdulrauf, S. I., M. Y. Kaynar, et al. (1999). "A
  comparison of the clinical profile of cavernous
  malformations with and without associated venous
  malformations." Neurosurgery 44(1) 41-6
  discussion 46-7.
• 55 patients
• 24 had CMs associated with VMs
• FM
• Greater risk of symptomatic hemorrhage (62 vs.
  38)
• More likely to have lesions in the posterior
  fossa (P0.001)
• Less likely to present with seizures
• Less likely to have family history

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Association with Down Syndrome

• There is no known association between Down
  syndrome and the development of CM
• Singh et al. (1993) reported on a 30 year-old
  male with Down sydrome and a cervical
  intramedullary CM (chance association)

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Familial Cavernomas

• Gunel, M., I. A. Awad, et al. (1996). "A founder
  mutation as a cause of cerebral cavernous
  malformation in Hispanic Americans." N Engl J Med
  334(15) 946-51.
• Studied 57 Hispanic patients
• 47 were from 14 different kindreds with familial
  CMs
• 10 were sporadic cases
• Found that all cases could be attributed to
  inheritance of the same mutation on 7q from a
  common ancestor with incomplete penetrance

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Familial Cavernomas

• Labauge, P., L. Brunereau, et al. (2000). "The
  natural history of familial cerebral cavernomas
  a retrospective MRI study of 40 patients."
  Neuroradiology 42(5) 327-32.
• 40 patients with 3.2 year follow-up
• 232 CMs, 5.9 per patient
• Hemorrhagic risk 2.5 per lesion per year
• 27.5 developed new CMs
• Incidence of new lesions 0.2 per patient year
• 3.9 of lesions in 22.5 of patients changed
  significantly in size

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Familial Cavernomas

• Labauge, P., L. Brunereau, et al. (2001).
  "Prospective follow-up of 33 asymptomatic
  patients with familial cerebral cavernous
  malformations." Neurology 57(10) 1825-8.
• Prospectively followed 33 asymptomaitic
  non-Hispanic patients with familial CMs for 2.1
  years
• Total of 234 CMs, mean 7.1 per subject, range
  1-85 CMs per subject
• 2 subjects became symptomatic (hemorrhage,
  seizure)
• 30 new lesions appeared in 10 subjects (46)
• 0.4 lesions per year
• Four lesions (1.7) increased in size in 3
  subjects (9.1)