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

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

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

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

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.

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

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

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]

Most 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.

0.5% of the population ~ 25% diagnosed before age 17 ~ % supratentorial Female preponderance; reason uncertain

May present with symptoms secondary to haemorrhage: new onset seizures Hydrocephalus [ superficial haemosiderosis ] neurological deficit also “Incidentaloma !!!”

MRI 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

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

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

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 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

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.

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 Jul;24(2-3):55-71Mottolese CHermier MStan HJouvet ASaint-Pierre GFroment JCBret PLapras C 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 May;42(5): Labauge PBrunereau LLévy CLaberge SHoutteville JP 3.Raychaudhuri R, Batjer HH, Awad IA. Intracranial cavernous angioma: a practical review of clinical and biological aspects. Surg Neurol Apr;63(4): Raychaudhuri RBatjer HHAwad IA 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 Mar;25(1-2):1- 55.Bertalanffy HBenes LMiyazawa TAlberti OSiegel AMSure U 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 Jun;24(5):631-7.Pinker KStavrou IKnosp ETrattnig S 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 Oct;36(10): Chooi WKConnolly DJColey SCGriffiths PD 7.Pozzati E, Acciarri N, Tognetti F, Marliani F, Giangaspero F. Growth, subsequent bleeding, and de novo appearance of cerebral cavernous angiomas. Neurosurgery Apr;38(4): Pozzati EAcciarri NTognetti FMarliani FGiangaspero F 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 Nov;22(11): Sürücü OSure UGaetzner SStahl SBenes LBertalanffy HFelbor U

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

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