|Conference and seminar notes|| Main project page|
Previous entry Next entry
Notes for European Conference in Neuro Radiology
Am just now catching up on notes.
Notes from ECNR: http://www.aimgroup.it/2008/ecnr_ott/sci%20info.html
Carlos Castano (Spain, former student Pierre)
Classifying vascular anomalies Tumors (endothelial hyperplasias) Malformations (normal endothelial cells)
Hemangioma is now termed a vascular tumor, can be part of PHACE, SWS, blue rubber bleb syndromes
Three kinds: Superficial (formerly capillary or strawberry) Mixed or deep (formerly tuberous or capillary cavernous type II, subcutaneous)
Low or high flow: low is venous, lymphatics, was “cavernous hemangioma”
Vascular tumors are not congenital. More frequent in females, in white races, rapid growth and slow regression. Rubbery/firm, not usually involving bone.
Vascular malformations on the other hand can lead to dysmorphy or bone hypertrophy and grows with the child.
Infantile hemangiomas are common affecting 4-10% of children under 1 y. Appear in the first six weeks. Slow regression over 5-8 years, involuted and replaced with fat. I was wondering about pericytes here.
All vascular tumors lead to increased expression of GLUT1 marker.
Large cervicofacial vascular tumor on screen led to impaired vision, they can even lead to heart failure.
PHACES syndrome involves posterior fossa problems, sometimes these are tumors, hemangioma, aortic arches, cardiac malformations? Eye anomalies, and sternum.
A “congenital” hemangioma is still a vascular tumor. This does not evolve like a common infantile hemangioma but can resolve by 14 months; if it doesn’t, it never will. It is GLUT1 negative. When does regress, there is necrosis in the center of the tumor and rapid regression.
Hemangioendothelioma is deep red/purple like a fresh bruise.
Vascular malformations have no sex ratio, all body parts can be affected. Always congenital even if not seen right off. No cellular proliferation but mural structure dilates, up to 35% is assoc with skeletal anomalies.
Capillary malformations also affect venules. Upper dermis. Nodular ecstasies. SWS. CAMS, AVMS. RASA1 mutation on 5q can lead to CAMS and AVM or AV fistula. Phakomatosis – Klippel-Trenaunay (pigmentovascularis). Once case caused by VG5Q.
Telangiectasias: dilated punctuate/stellar/linear capillary like. If you apply pressure, get blanching.
Rendu-Osler-Weber – GI telangiectasias, there are AVMS, the skin lesions appear later. Often seen in the face or mucous membranes for these. Propensity to bleed – AV shunts because of anomaly in the arteries/arterioles. Can embolize to treat, like varicose veins.
Venous malformations: dysplastic venules. Thin-walled but the ECs are normal. Often get clots, fibral ingrowth, phleboliths. Present at birth but grow and expand esp after puberty or trauma or surgery. Blue and soft. Segmental distributions (remember the big face that Pierre often shows). If autosomal dominant can be more widespread but very common in head and neck. Commonly on the masseter/muscles not so much within them but on surface.
Sinus pericranii – extracranial veins communicate with intracranial dural sinus without any emissary/diploic veins. No communication with the arteries. Mostly midline, asymptomatic, often frontal. A mass eg vein up the outside of skull, up over the fontanelle.
Blue rubber bleb affects GI tract or cutaneous. Massive hemorrhage leads to anemia, mostly affects upper limbs and trunk. Flat ECs but deficient SMCs. More and more lesions with growth. Have embolized.
Lymphatic malformations: 75% in head and neck. Sometimes fibrotic reaction around these. No sex/race ratio. Macrocystic = cystic hygroma. If in the floor of mouth, cheek or tongue, usually microcystic = lymphangioma. Often assoc with bone/soft tissue anomalies. Can be mixed. Treatment perhaps with picibanil (?) to get inflammatory reduction and regression.
AVMs: least common of above. Midface (cheek/ear) most common. Often AV shunts, grow with child and recruit nearby vessels. AV fistula is single and can be either congenital or acquired. Do not empty when pressed. Needs angiography. Catheters into all feeders can get full embolization. Followup wih plastic surgery because can regrow. Visible with artery leading to nidus leading to vein.
Dural AV fistulas can have sinus malformation where the AV shunt is secondary. This can still kill children at birth. Infantile form leads to secondary jugular occlusions, large sinuses. Adult form has small sinuses.
Vein of Galen aneurismal malformation versus simple dilation. The former is an AV shunt in the wall of the embryonic precursor, which is the medial vein of the prosencephalon (MVP). This can be choroidal – extracerebral and subarachnoid. Arterial feeders are bilateral. Can also exist in a mural form with the fistula in the wall of the MVP and suppliers in this case are posterior or collicular choroidal arteries.
If dilation it is draining normal brain tissue as well as the AVM. Both can lead to hydrocephalus.
Craniofacial CAMS/CVMS. Jo’s picture of CAMS I, II, III (I = frontonasal bud, II = mesencephalon, III = rhombencephalon and pharyngeal arch 2). SAMS I is similar but in the occipital region and medulla (segmental or somatic?) I affects tip of nose, philtrum of lip, extends back to optic nerve and hypothalamus.
CVMS – along the trigeminal region showed example, can be uni- or bilateral.
SWS can have meningeal malformation. Moya-moya mentioned with stenosis or occlusion of supraclinoid (?) part of the internal carotid and adjacent middle/anterior cerebral arteries being the pathognomic main sign. Then get bypasses. Ischaemia in children. Affects 5% kids, 65% adult (what does that mean?). Above all, leads to aneurisms.
Vitor Pereira, former student of Pierre’s, now in Geneva:
Congenital vascular malformations
He is making distinction between anomaly and malformation. But this is not very convincing re: Carlos Castanos’ distinctions for tumors.
Primary vs. secondary architectural features. Eg flow-related lesions esp arterial side.
Separation between true cause of lesion and clinical presentation – doctors can call such late-presentation malformations congenital but that is not a universal term because of the conflation with the presentation which itself may not be congenital.
Cover vascular development a little? And head segmentation again.
Case of CAMs with tip of nose and philtrum: Jiarakongmun et al. (can’t find though) 2002. Craniofacial arteriovenous metameric syndrome cf Bhattacharya J et al. and a CAMS3 example as well.
Pierre’s concept of “causative trigger” affecting an upstream cell, then a “revealing” trigger. Much like two-hit hypothesis. Also termed a “dormant” effect – can be transmissible. Cf. Gibbons GH and Dzau VJ 1994.
Also Pierre’s example of cerebrofacial venous metameric syndrome – classify as 1, 2 etc. Facial and intracranial lesions are linked of course.
“Pre-pathological” stage w/o disease. Somatic mutation he called “genetical” stage – transmission to a clonal group of cells and their descendants at the “biological” stage. Second trigger actually responsible for “preclinical or morphological” stage and then clinical onset.
Each disease can be applied to a timeline in which potential gets more restricted and the second insult has occurred yet or not. The AVM does not grow itself (though can induce 2e changes) because it is restricted in the place where it can be revealed.
Secondary effect high flow fistula leading to “melting brain” syndrome – developing brain will suffer degeneration .
A large nidus is not growth of a small one.
Blue rubber bleb nevus syndrome: missense activating mutations in TIE2.
(What about Parkes-Weber? RASA1 activating?)
Olof Frodman: CSF circulation
Production in choroid plexus tucked into the middle, flow through 4th ventricle into basal cisterns, then around SC and around front, up to top of the front of the brain where reabsorbed by capillaries – not by arachnoid villi themselves (pacchionian granulations). But these only develop at 2y postnatal. Olof speculates their function may be related to pressure regulation.
Cf. Greitz D Neurosurg Review 2004. “Bulk flow” is out and revised BBB model for reabsorption is in.
Reabsorption via Virchow-Robin spaces / perivascular spaces / “space of His” in continuity with sub-pial area. Funnel-like extensions of pia along penetrating vessels. Further in, this pia will actually merge into the basal membrane of the artery; no more perivascular space.
This space is between the pericytes and the glia limitans. Lots of mononuclear cells in this space.
Difference between cerebral/CNS and general capillaries. ECs have tight junctions between them, then outerlying sparse pericytes and sealed by the glial end-feet.
Rapid transport for albumin from CSF to blood or brain – 90 minute half-life. Also contrasting agents, within an hour or two. After a day or two, entire clearance to blood. His conclusion that there is a one-way gating – get from CSF to blood easily, pretty free exchange of course between CSF and brain itself.
Blood proteins 200x more than CSF. Active transport out of CSF through EC’s. Several “efflux transporters” – will bring back hundreds of papers from PubMed. Must have simultaneous massive exchange of water.
Lots of aquaporins in brain. See this review. AQP4 mutant mice get worse HC after obstructive kaolin injection than not, implying that AQP4 mediates active water egress from brain parenchyma into interstitial space.
Also pulsatile motion in CNS, particularly in center of brain and posterior fossa), rather piston-like.
Increased pressure b/c of Pascal’s law is transmitted by the speed of sound in water to all other spaces in closed system. Can have not static but only dynamic pressure gradients conducted by movements of volume (cf systolic influx into COMPLIANT arteries) and some goes out through the veins (2/3) but 1/3 through CSF flow through the foramen magnum into spinal canal. This is compliant – elastic - and widens with every systolic beat, flows back in diastole.
In normally compliant artery, these will dampen pressure via Windkessel mechanism. If non-compliant the pulse pressure is transmitted into brain leading to hydrocephalus. As CSF flows out normally, presses on bridging vein so only partly blood goes out, partly presses into the CSF and sends it into spinal cord.
You need an opening pressure to open the collapsible veins. Once overcome, gets easier and much more flow and following that, linear relation between pressure and flow. Optimally, veins should neither collapse nor be fully extended. The partial obstruction at end of bridging veins (exit) keeps the right level of pressure.
I would have liked to see the hydrocephalus version but should be able to figure it out.
Immunological situation - T cells present in the perivascular space as well as scavenging phagocytes. Only in that space and not in the brain itself. Accumulation in these space is a precursor sign of demyelination and multiple sclerosis as well as after trauma. Cf Wuerfel J et al in Brain 2008. Less water and more cells as opposed to normal CSF circulation. Apparently need macrophages to facilitate entry of the T cells.
MS plaques are formed on perivenular spaces, always perpendicular to the ventricular wall. Cf images in Ge Y et al AJNR 2005. Plaques grow on the vessels from the perivascular spaces.
Also in trauma. General reaction in brain, not just at injury site. Early phase, get perivascular inflammation. Later phase – 3-5d – in the parenchyma. Perhaps the enlargement of PV spaces reflect accumulated inflammatory cells. Leads to irreversible dilation to unknown effect, esp visible in young people who have less of this space.
What is normal PV space? Anterior commissure often find the largest ones, also midbrain, and posterior cortext. Can see dramatically enlarged/dilated PV spaces but as incidental findings – don’t mistake for cystic tumours or masses. Most commonly associated with age.
Pia Sundgren – USA and Malmö, Sweden
Cystic malformations of posterior fossa. Cf. Tortori-Donati P et al. 1996, modified in 2004.
Two groups : 4th ventricle roof, leading to anomalies of ant membranous area, hypoplasic cerebellum leading to Dandy-Walker. If posterior membranous area leads to Blake complex, mega cisterna magna. If meningeal malformation, arachnoid cyst, non-communicating
DW agenesis of vermis, rotation counterclockwise to rise in posterior fossa and 4th centricle grows into cyst enlarging post fossa. Hemispheres not so affected.
Flat roof of 4th ventricle yields after choroidal fold into anterior and posterior areas. AMA will get swallowed into choroids plexus but posterior remains. DWS gets persistent AMA and then CSF pulsation and ballooning out. The hypoplastic vermis is rotating counterclockwise out and above the hemispheres. Barkovich described less severe forms of DW along a spectrum. Generalized cerebellar hypoplasia.
Can be assoc with occipital meningocoele – perhaps because occipital bone ossifies late and will incorporate the pressure of CSF going out. Clinical outcome – nearly half have normal intelligence and mild symptoms (perinatal more risky though). Others developmental delay.
Differential diagnosis: Blake’s pouch gets HC needing shunting, failure of permeabilization of posterior membranous area (PMA). Caudal protrusion, collection of retro/infracerebellar CSF.
Mega cisterna magna needs no treatment, perhaps a continuum of Blake’s pouch if the permeabilization happens late in the pouch (under pressure?). No “mass effect” and normal vermis.
Arachnoid cyst can induce HC, non-communicating with CSF. Usually retroinfracerebellar or posteriorly. No other malformations, but cause a mass effect (HC from aqueduct compression).
Neurorad should separate into right groups to guide neurosurgeons as to treatment – cystoperitoneal shunting or not.
Joubert syndrome – clinically apnea, ataxia, nystagmus. Molar tooth appearance because of hypoplasia of vermus and thickened peduncles. Other related oculo-cerebello-renal syndromes. Senior-Löken, COACH syndrome and Arima syndrome – requires additional abdominal ultra0sound. “Batman wing” appeance as the hemispheres swing back around.
Via MR more cases of rhombencephalosynapsis have been observed. Lack of septum pellucidum, abnormal cortical alignment. No vermis, midline fusion of hemispheres and abnormal colli. Then leads to Chiara malformation (tonsillar herniation so type I). Chiari II is due to not enough CSF as leaks out of a lower myelomeningocoele and posterior fossa doesn’t swell out under CSF pressure, so everything crowded in. The Chiari I is due to underdeveloped occipital bones.
Agenesis of cerebellum paradoxically not so symptomatic as that?
Pontocerebellar hypoplasia – normalish posterior fossa but reduced cerebellar folia, much smaller pons, hemispheres and vermis – though it’s proportionally small. Enlarged subarachnoid spaces.
Unilateral isolated cerebellar hypoplasia can be with Aicardi syndrome, facial hemangioma or ipsilateral cutaneous “organoid” nevus.
Cerebellar cortical dysplasia – disorganized eg Lhermitte-Duclos disease (phakomatosis?). Cf O Naggara in France. Anomalies of foliation.
Other syndromes: lissencephaly with cerebellar hypoplasia (two genes known of 6 variants named a-f). Kinking of pons like WWS but creatine was normal not elevated; LISS1 was normal. Showed the first MRI of LCHc.
Walker-Warburg: O-mannosyltransferase-1 (POMT1; 607423) and -2 (POMT2; 607439). Individual patients with WWS have been shown to have homozygous mutations in the FKRP (606596) and LARGE genes (603590), respectively. A phenotype consistent with Walker-Warburg syndrome has been shown to be caused by mutation in the fukutin gene (FKTN; 607440), the same gene that causes the less severe Fukuyama congenital muscular dystrophy (FCMD; 253800). Cerebellar vermis hypoplasia, dysplastic cortex and hypoplastic brainstem and pons with a posterior kinking of the pons.
Muscle-eye-brain disease. Type II cobblestone complex with lots of cysts as well as vermian cerebellar vermis and anterior pons. Enlarged eye. Microcysts, polymicrogyria. muscular dystrophy and neuronal migration disorder that characterize muscle-eye-brain (MEB) disease are caused by mutations in O-mannose beta-1,2-N-acetylglucosaminyltransferase (POMGNT1; 606822), which participates in O-mannosyl glycan synthesis.