Management of Cavernomas in the Paediatric Population

What is a cavernoma?

Vascular lesions of the CNS, also known as cerebral cavernous malformations or angiographically-occult arterio-venous malformations

Represent a surgically correctable cause of epilepsy in the paediatric population

Case 1• KM. 9 year old boy• New onset complex partial seizures with right frontal

discharges • Seizure activity well-controlled on sodium valproate,

levetiracetam, and carbamazepine • Imaging suggested cavernoma

Mesh of thick walled vessels

Peri-lesional Haemosiderin

Possible rupture point

Lumen

Craniotomy & Excision

Case 1• MS. 9 year old male• New onset complex partial seizures with right frontal

discharges • Seizure activity well-controlled on sodium valproate,

levetiracetam, and carbamazepine • Imaging suggested cavernoma

• Follow – Up – Seizure frequency ↓– No deficit

Case 2• MK. 10 year old girl• 8 month hx of simple & complex partial seizures

secondary to right tempero-parietal lesion• Failed multiple single & combination anti-convulsants

failed – Side – effects – Fatigue & Poor school performance

• Imaging

Hyalinised Thick Walled Vessels [TWV] – Partly thrombosed [T]

TWV

T

Stealth-guided parietal craniotomy en-bloc resection of lesion + rim of haemosiderin-stained tissue

Case 2• MK. 10 year old female • 8 month hx of simple & complex partial seizures

secondary to right tempero-parietal lesion• Failed multiple single & combination anti-convulsants

failed – Side – effects – Fatigue & Poor school performance

• Uneventful post-operative recovery. • Seizure free in immediate post-operative

period.

Case 3• SC. 20 year old woman• 18 yrs → two episodes of new onset seizures • Imaging demonstrated left frontal 2cm x 2 cm lesion, ??

arterio-venous malformation• Carbamazepine initiated. • Cerebral angiography normal

Stealth-guided left frontal craniotomy and excision of lesion

Vessel Wall Remnants [VWR]

VWR

Lumen

Hemosiderin

Vessel Wall Remnants

Elastic

Siderocalcinosis – perilesional

Vascular Malformation remnants – Angio Negative – probable Cavernoma

Case 3• SC. 20 year old woman• 18 yrs → two episodes of new onset seizures • Imaging demonstrated left frontal 2cm x 2 cm lesion, ??

arterio-venous malformation• Carbamazepine initiated. • Cerebral angiography normal

• Uncomplicated recovery and discharged home on post-operative day 4

Natural History• Cavernomas may be multiple, ranging from 1-12 • Size range from 0.1cm - 9cm • Risk of haemorrhage estimated to be 2.5%

annually [cumulative].

• Risk of new onset seizures is 1.51% annually [cumulative]

Aetiology of CavernomasMost are sporadic.

Risk factors include:• previous radiotherapy to brain • more than one first degree relative with

cavernoma.

• 70% of patients with familial cavernomas carry a frameshift mutation for either KRIT1 / CCM1, MGC4607 / CCM2, or PDCD10 / CCM3, mapping, respectively to chromosomes 7q, 7p, and 3q.

Incidence• 0.5% of the population• ~ 25% diagnosed before age 17• ~ 63 - 81% supratentorial • Female preponderance; reason uncertain

PresentationMay present with symptoms secondary

to haemorrhage:

• new onset seizures • Hydrocephalus [superficial haemosiderosis]• neurological deficit

also “Incidentaloma !!!”

RadiologyMRI appearance:• “mulberry” nodules with mixed

signal intensity• peripheral haemosiderin rim is

seen as an area of decreased signal intensity on T2-weighting and as an area of mixed signal intensity on T1-weighting

• no visible feeding vessels, surrounding oedema, or mass effect.

Angiographically occult

Histopathology• Dilated sinuses [DS]• Thin vessel walls [TWV] usually lack

smooth muscle, elastin, and intervening parenchyma

• Electron-microscopy endothelial cells → poorly developed tight junctions, allowing for micro-haemorrhages → characteristic haemosiderin staining.

• Haemosiderin rim surrounded by reactive gliosis.

• Thrombosis [T] may be present Haemosiderin

TWV

DS

T

Why Surgical Excision?

1. Reduces need for long-term anti-convulsants

2. Attainment of intellectual and learning objectives

3. Avoid “labelling” of child as “epileptic”

4. ↓ long-term risk of haemorrhage

Cavernoma Surgery• Stealth-guided Craniotomies• Excision not only of the cavernoma itself

(lesionectomy), but also excision of haemosiderin ring, surrounding gliosis.

• In certain cases, may proceed to hippocampectomy. (Varies centre to centre)

Seizure control appears to be better in patients who had excision of haemosiderin ring. However, a clear correlation between extent of resection and seizure control has yet to be established.

Post-Operative Seizure Control

Post-operative seizure control is dependent on: two factors:

1. Length of time the patient was symptomatic pre-operatively. [The shorter the duration of pre-operative seizures, the more likely it is

the patient will be seizure-free post-operatively].

2. ?? Extent of the surgical procedure

Cavernoma Surgery• Prognosis following surgical excision is usually

good• Overall morbidity in most centres is around 4%. • With complete excision of the lesion, the risk of

haemorrhage is non-existent.

Conclusion• Cavernomas represent an uncommon but

treatable cause of epilepsy and cerebral haemorrhage in the paediatric population.

• Symptomatic children diagnosed and treated early will have a better post-operative result

References

1. Mottolese C, Hermier M, Stan H, Jouvet A, Saint-Pierre G, Froment JC, Bret P, Lapras C. Central nervous system cavernomas in the pediatric age group. Neurosurg Rev. 2001 Jul;24(2-3):55-71

2. Labauge P, Brunereau L, Lévy C, Laberge S, Houtteville JP. The natural history of familial cerebral cavernomas: a retrospective MRI study of 40 patients. Neuroradiology. 2000 May;42(5):327-32.

3. Raychaudhuri R, Batjer HH, Awad IA. Intracranial cavernous angioma: a practical review of clinical and biological aspects. Surg Neurol. 2005 Apr;63(4):319-28.

4. Bertalanffy H, Benes L, Miyazawa T, Alberti O, Siegel AM, Sure U. Cerebral cavernomas in the adult. Review of the literature and analysis of 72 surgically treated patients. Neurosurg Rev. 2002 Mar;25(1-2):1-55.

5. Pinker K, Stavrou I, Knosp E, Trattnig S. Are cerebral cavernomas truly nonenhancing lesions and thereby distinguishable from arteriovenous malformations? MRI findings and histopathological correlation. Magn Reson Imaging. 2006 Jun;24(5):631-7.

6. Chooi WK, Connolly DJ, Coley SC, Griffiths PD. Assessment of blood supply to intracranial pathologies in children using MR digital subtraction angiography. Pediatr Radiol. 2006 Oct;36(10):1057-62. .

7. Pozzati E, Acciarri N, Tognetti F, Marliani F, Giangaspero F. Growth, subsequent bleeding, and de novo appearance of cerebral cavernous angiomas. Neurosurgery. 1996 Apr;38(4):662-70.

8. Sürücü O, Sure U, Gaetzner S, Stahl S, Benes L, Bertalanffy H, Felbor U. Clinical impact of CCM mutation detection in familial cavernous angioma. Childs Nerv Syst. 2006 Nov;22(11):1461-4.

Hyalinised Thick Walled Vessels [TWV] – Partly thrombosed [T]

T

TWV

Hyalinised Thick Walled Vessels [TWV] – Partly thrombosed [T]

TWV

T