Transcript CHLA Case Presentation - Keck School of Medicine of USC

CHLA Case Presentation
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
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
Differential Diagnosis
• Cavernous malformation
• Teratoma
Procedure
Posterior fossa craniotomy with gross
total resection of mass
Diagnosis
Cavernous Malformation
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
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
Cavernous Malformation
• 9% of all types of brain vascular
malformations
• Prevalence is 0.4-0.8%
• M:F ratio is1:1
• Age at presentation 20-40
• Present with headache, focal
neurological deficit, seizures,
hemorrhage
Cavernous Malformation
• CM can repetitively
hemorrhage resulting in
– Gliosis
– Tissue discoloration
– Hemosiderin-laden
macrophages
– Microcalcification
– Hyalinization
– Cysts with blood breakdown
products
Cavernous Malformation
• Can be familial
– Hispanic families
• CCM1, 7q11-21
– Non-Hispanic families
• CCM2, 7p13-15
• CCM3, 3q25.2-27
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
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 CM’s associated with VM’s
–
–
–
–
–
F>M
Greater risk of symptomatic hemorrhage (62% vs. 38%)
More likely to have lesions in the posterior fossa (P=0.001)
Less likely to present with seizures
Less likely to have family history
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”)
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
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
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%)