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Brain: Pathology-Based Diagnoses cerebellum itself, aswellabnormalitiesofthe surrounding cerebellar leptomeninges mayresultinanomalies ofthe overlying leptomeninges. Therefore,abnormalities ofthe discovered. Severalcerebellargrowth factorsderivefromthe cerebellum. Thereasonforthis hasonlyrecentlybeen fossa maybeasignofassociated anomaliesofthe dysmorphic. Rememberthatlarge CSFspacesintheposterior interhemispheric cysts,whenthe commissuresareabsentor leptomeninges, suchasinterhemispheric lipomasand for otheranomaliesassociatedwithabnormalmidline are importantincommissuraldevelopment,sobesuretolook eminence ofthehypothalamus.Themidlineleptomeninges pituitary lobeisinthesellaturcicaandnotmedian hypothalamus andpituitaryglandtoensurethattheposterior anomalies ofthehypothalamus,soalwayslookat described. Manyofthesemalformationsareassociatedwith more than130syndromesinvolvingthemhavebeen commissures arethemostcommonbrainmalformations; craniocervical junction.Anomaliesofthecerebral anomalies ofthecerebellarvermis,and tumors (suprasellar,pineal,brainstem,and4thventricle), anterior commissure,andhippocampalcommissure),midline anomalies ofthecerebralcommissures(corpuscallosum, processes ofchildrentakeplaceinthemidline,including Evaluate themidlinestructuresfirst,asmanydisease scrutinized ineverypatient. structures (brainstemandcerebellum)shouldallbe interhemispheric fissure,andthemidbrainhindbrain completely presentandofnormalsizeshape),the clefts), thebasalganglia,ventricularsystem(allventricles cerebral whitematter(myelination,presenceofnodulesor pattern, andcorticalgraymatter-whitematterjunction),the hypothalamus), thecerebralcortex(corticalthickness,gyral and rhinencephalon,pituitarygland,opticchiasm, (including cerebralcommissures,septumpellucidum,nose take placeinanorderlymanner.Themidlinestructures After acquisitionofappropriateimages,imageanalysismust in thenearfuture. particularly inthebrainstem,andmaybecomeclinicallyuseful better understandtheconnectivityofmalformedbrain, anisotropy (FA)mapsandperformtractographyisusefulto diffusion tensorimaging(DTI)toacquirecolorfractional helpful inevaluatingforfocalcorticaldysplasia.Theuseof nerves. High-resolution3DFLAIRimagesmaybeparticularly evaluation ofmidlinestructures,hippocampi,andoptic resolution 2DcoronalT2imagesremainaworkhorsefor volumetric imagesareessentialforthispurpose.High- of subtleabnormalities.High-resolutionT1-weighted high resolutionandabilitytoreformatwillaidinthediagnosis can bereformattedinanyplaneorasasurfacerendering.The acquired asvolumetricdatawheneverpossiblesothatimages matter andwhitematter,havehighspatialresolution,be imaging sequencesshouldmaximizecontrastbetweengray be gearedtowardshowingastructuralabnormality.The guarantee ofanormalbrain.Inallsuchcases,imagingshould malformation isevenhigher,butanormalappearanceno facies, hypotelorism),thelikelihoodofanunderlyingbrain child appearsdysmorphicinanyway(low-setears,abnormal brain malformationshouldbecarefullyinvestigated.Ifthe either seizuresordelayeddevelopment,thepossibilityofa Whenever aninfantorchildisreferredforimagingbecauseof Malformations A GeneralImagingApproachtoBrain Approach toBrainMalformations generated inthe medialandlateralganglioniceminences, the migration disorders, astheyareformedfromneurons The basalganglia aresometimesabnormalinneuronal- isointense tograymatteronall sequences. weighted imagesorFLAIR toensurethatthelesionis matter onT1-weightedimages, sobesuretolookatT2- difficult todifferentiatefromunmyelinated orinjuredwhite subependymal/periventricular region. Heterotopiamightbe nodular heterotopiaismorelocalizedtotheimmediate way tothelateralventricularwall,whereasperiventricular matter heterotopiatypicallyextendsfromthecortexall periventricular ordeepwhitematter.Transmantlegray Also, lookfornodulesofheterotopicgraymatterinthe the windowonFLAIRimagesincreasesconspicuityofFCD. lateral ventricle(knownasthetransmantlesign).Narrowing coursing fromthecortextosuperolateralmarginofa where onemayseeacurvilinearcone-shapedabnormality myelination, FCDsaretypicallymostconspicuousonFLAIR, with ↑T1&↓T2inthesubcorticalwhitematter.After cortical dysplasias(FCDs)areoftenmostconspicuousatbirth ipsilateral hemisphere&ventricularenlargement.Focal hemimegalencephaly, whichisoftenaccompaniedby malformation shouldpromptonetothinkof signal inthewhitematterofaneonatewithoverlyingcortical cytomegalovirus infection.Generalizedipsilateral↑T1&↓T2 polymicrogyria shouldraisesuspicionforcongenital hypomyelination oramyelinationassociatedwithoverlying within thedeepwhitematter.Diffuselayersof textbooks). Then,lookforareasofabnormalmyelination normal myelinationcharts,includingjournalarticlesand myelination isappropriateforage(therearemanysourcesof After thecortex,lookatcerebralwhitematter.Makesure thinning isfocalormultifocal. a prenatalinjury(infectiousorischemic),particularlyifthe with diminishedunderlyingwhitematter,oneshouldthinkof abnormality. Ifthecortexisabnormallythinandassociated important tobespecificinreportingthelocationof bilateral parasagittalparietooccipitalpolymicrogyria;itis different entitythanbilateralperisylvianpolymicrogyriaor the polymicrogyria.Bilateralfrontalpolymicrogyriaisa polymicrogyria syndromesthatdependuponthelocationof a mutationofDCX.Similarly,therearemanydifferent whereas pachygyriathatisworstinthefrontallobessuggests TUBA1A (isalsoassociatedwithmicrocephaly), the parietalandoccipitallobessuggestsamutationofLIS1or muscle-eye-brain disease.Pachygyriathatismoreseverein associated withcongenitalmusculardystrophies,suchas syndromes, amongothers.Cobblestonecortexmaybe disorders, includingcongenitalcytomegalovirusandgenetic cobblestone cortex.Polymicrogyriaisseeninmanyunderlying irregular? Ifitisirregular,thinkofpolymicrogyriaor polymicrogyria. Isthecorticalwhitematterjunctionsmoothor normal (2-3mm)?Ifitistoothick,thinkofpachygyriaor to inside.Startwiththecerebralcortex.Isthickness After lookingatthemidline,evaluatebrainfromoutside by 10years,itshouldbeabout1.5:1. midline imagesis5:1or6:1.By2years,itshouldbe2.5:1,and normal neonate,theratioofcranialvaulttofaceon head sizethroughassessmentofthecraniofacialratio.In Looking atthemidlineimagealsogivesanideaofrelative the cerebellumitselfandofoverlyingleptomeninges. Walker malformation;itrequiresabnormaldevelopmentof CSF spaces.ThisisthebasisfordevelopmentofDandy- 5 Brain: Pathology-Based Diagnoses Findings Desikan RS et al: Malformations of cortical development. Ann Neurol. Ann development. cortical of Malformations al: et RS Desikan MR. CT Ultrasound Semin 80(6):797-810, 2016 malformations. fossa Posterior K: Shekdar 32(3):228-41, 2011 Thick cortex, smooth inner margin, few shallow sulci smooth inner margin, Thick cortex, matter junction Nodular cortex & gray matter-white margin, abnormal myelin Thick cortex, irregular inner junction, ± deep sulcus Thick cortex, blurred gray-white matter; dysplastic neurons ↑ T1, ↓T2 in neonatal white hypomyelination Delayed myelination, patchy Deep layers of hypomyelination/gliosis extending toward ventricle "Tail" of signal abnormality ON hypoplasia, pituitary anomaly, ± PMG/schizencephaly Varying degrees of incomplete hemispheric separation Absent septum typically thought to be destructive abnormal, refer to an axial or coronal image to make sure the abnormal, refer to an axial or coronal image are vermis is present; if the cerebellar hemispheres make a diagnosis continuous without a vermis between them, stenosis is of rhombencephalosynapsis. Whenever aqueductal If encountered, look carefully for rhombencephalosynapsis. shape (with a the 4th ventricle has an abnormal rectangular isthmus and small horizontal superior margin) with a narrow To confirm this vermis, consider a molar tooth malformation. tooth sign of the diagnosis, look on axial images for the molar superior lower midbrain, consisting of large, horizontal toward the cerebellar peduncles extending posteriorly superior vermis. cerebellum, and a longitudinal cleft in the are of normal size; Make sure that the brainstem components double that of the in a child, the height of the pons should be at the size of midbrain on the midline sagittal image. Looking vermis can the pons compared to that of the cerebellar of the anterior pons provide an important clue. Because much cerebellar is composed of the decussation of the middle peduncles, development hypoplasia of the cerebellum is nearly always associated with hypoplasia of the ventral pons. If the pons is normal in the setting of a small cerebellum, it is most likely that the cerebellum lost volume near the end of gestation or after birth. Remember that in a small posterior fossa, intracranial hypotension, or intracranial hypertension can result in descent of the cerebellum below the foramen magnum. Look for causes of a small posterior fossa (clival anomaly, anomaly of the craniovertebral junction), intracranial hypertension (space-occupying mass, hydrocephalus), or evidence of intracranial hypotension (large dural venous sinuses, large pituitary gland, "slumping" brainstem) before making a diagnosis of Chiari 1 malformation. Finally, remember to look at the size of the CSF spaces in the posterior fossa, enlargement of which may be a sign of abnormal leptomeningeal development. Selected References 1. 2. Approach to Brain Malformations to Brain Approach Agyria/pachygyria Polymicrogyria Cobblestone cortex Focal cortical dysplasia Hemimegalencephaly Cobblestone cortex Congenital cytomegalovirus Focal cortical dysplasia Septo-optic dysplasia Holoprosencephaly Malformations with severe prolonged hydrocephalus Brain Anomaly Imaging Checklist Imaging Brain Anomaly ON = optic nerve; PMG = polymicrogyria. Anomaly Anomalies of Cerebral Cortex Anomalies of With Cortical Malformation White Matter Abnormalities With Absent Septum Pellucidum Malformations Associated same germinal zones that produce GABAergic neurons that same germinal zones that produce GABAergic the basal ganglia migrate to the cerebral cortex. In particular, with tend to be dysmorphic in appearance in patients are often subcortical heterotopia. In addition, the hippocampi In patients abnormal in cortical-development malformations. are with lissencephaly, in particular, the hippocampi structural incompletely folded. Sometimes the only delay are abnormalities in children with developmental fully folded and not hippocampal; always ensure that they are carefully too round. In the case of longstanding seizures, and increased inspect the hippocampi for asymmetric atrophy signal to suggest hippocampal sclerosis. fissure (IHF); if the Always look at the entire interhemispheric the midline, cerebral hemispheres are continuous across In severe holoprosencephaly should be diagnosed. absent, whereas in holoprosencephalies, the IHF is completely areas of the IHF milder forms of holoprosencephaly, certain will be absent (anterior IHF in semilobar holoprosencephaly, central IHF in syntelencephaly). Look at the septum pellucidum; absence of the septum is seen in corpus callosum dysgenesis/agenesis and septo-optic dysplasia. When septo- optic dysplasia is identified, look carefully for pituitary abnormalities, most commonly an ectopic posterior pituitary. Additionally, whenever septo-optic dysplasia is suspected, a careful search for associated schizencephaly or polymicrogyria is warranted. If present, a diagnosis of septo-optic dysplasia plus is established. While checking the septum, look at the lateral ventricles to ensure they are normal in size and shape. Abnormally enlarged trigones and temporal horns are often associated with callosal anomalies and pachygyria. Enlarged frontal horns are often seen in bilateral frontal polymicrogyria. Remember to look carefully at the posterior fossa; anomalies of the brainstem and cerebellum are commonly overlooked. Make sure that the 4th ventricle and cerebellar vermis are normally sized. In newborns, the vermis should extend from the inferior colliculi to the obex, whereas infants and older children should have a vermis that extends from the intercollicular sulcus to the obex. Also, make sure you see normal vermian fissures. If the fissuration of the vermis looks 6

Brain: Pathology-Based Diagnoses lipomas. finding inlargetubulonodular the fattymass,acommon enveloping ofvessels﬉by dysgenesis ﬊.Notethe severe associatedcallosal pericallosal lipoma﬈and T1WI MRshowsalarge anomalies. (Right)Sagittal carefully forassociated callosum isuncommon,solook dysgenesis ofthecorpus the corpuscallosum.Isolated splenium ﬈&rostrum﬊of Note thepoorlyformed & dysmorphiccorpuscallosum. anomalies showsashort,thin, year oldwithmultiple (Left) SagittalT1WIMRina7 callosal abnormalities. development arecommonin Malformations ofcortical matter heterotopia﬈. periventricular nodulargray extensive bilateral with callosalagenesis﬊& Axial T2WIMRina4yearold of subtleFCDlesions.(Right) means toincreasingdetection Windowing isanimportant greater windowingcontrast. the imageonrightwith is muchmoreconspicuousin windowing. NotehowtheFCD with varyingcontrast dysplasia (FCD)type2B﬈ a 3yearoldwithfocalcortical (Left) CoronalFLAIRimagesin congenital CMV. ﬊, findingsoftenseenin white matterabnormalities polymicrogyria ﬈.Notethe sulci, consistentwith GM-WM junctionwithshallow cortical surface&anirregular thickening withirregular congenital CMVshowscortical T2WI MRina4yearoldwith brain volume.(Right)Axial enlarged secondarytosmall pachygyria. Ventriclesmaybe frontal lobes,consistentwith ﬈ symmetricallywithinboth gyri anddecreasedsulcation marked thickeningofmultiple year oldwithseizuresshows (Left) CoronalT2WIMRina1 Approach toBrainMalformations Focal CorticalDysplasia Callosal Dysgenesis Pachygyria Subependymal GrayMatterHeterotopia Callosal DysgenesisWithPericallosal Polymicrogyria inCongenital Cytomegalovirus Lipoma 7 Brain: Pathology-Based Diagnoses (Left) Axial T2WI MR in a 13 year old with oral digital facial syndrome shows thickened superior cerebellar peduncles ﬈ & typical anterior clefting ﬊ of the midbrain, consistent with a molar tooth sign. The molar tooth sign is associated with a number of various conditions. (Right) Sagittal T2WI in an infant with classic Dandy-Walker malformation shows marked cystic enlargement ﬈ of the posterior fossa in continuity with the 4th ventricle, hypogenetic cerebellar vermis ﬊, & elevation of the torcula Herophili ﬈. Coronal T2WI MR in a 5 (Left) Coronal T2WI septo-optic year old with absence of dysplasia shows & a very septum pellucidum ﬊ . Right small left optic nerve ﬈ optic nerve looks grossly normal in size. Asymmetric is very optic nerve hypoplasia common in this diagnosis. (Right) Axial T1WI MR shows lined bilateral schizencephaly The by dysplastic gray matter. & the right side is open lip ﬊ left is closed lip ﬈. Again note the bifrontal polymicrogyria ﬉ & absence of the septum pellucidum st in this patient with septo-optic dysplasia plus syndrome. (Left) Axial T2WI MR in a 2 year old with semilobar holoprosencephaly shows absence of the septum pellucidum ﬈, fused thalami ﬊, & extension of gray matter ﬈ across the posterior midline. Also note the near absence of the frontal horns & the azygos anterior cerebral artery ﬉. (Right) Axial T2WI MR in a 3 year old with aqueductal stenosis & rhombencephalosynapsis shows absence of the cerebellar vermis with extension of cerebellar white matter tracts ﬈ across midline. Dysplasia Rhombencephalosynapsis Dandy-Walker Malformation Bilateral Schizencephaly in Septo-Optic Bilateral Schizencephaly Approach to Brain Malformations to Brain Approach Septo-Optic Dysplasia Septo-Optic Semilobar Holoprosencephaly Joubert Syndrome & Related Disorders