CHLA Case Presentation

HistoryHPI: 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%)