52 2Journal ofNeuroloD,, Neurostirgery, aoid Psychiatry 1996;61:52-56

Congenital unilateral perisylvian : J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.61.1.52 on 1 July 1996. Downloaded from radiological basis and clinical correlations

G Sebire, B Husson, A Dusser, Y Navelet, M Tardieu, P Landrieu

Abstract Over several years, we have identified in our Design-Advances in neuroimaging have centre a distinct group of six children presenting allowed correlations between radiological with unilateral perisylvian structural anomalies patterns and clinical features of on neuroimaging. The clinical and EEG fea- malformations. This paper reports clini- tures associated with this radiological pattern, cal, prognosis, and electroencephalo- together with a review of cases selected from graphic features of six children with a the medical literature, allowed us to define a previously unrecognised neuroimaging "congenital unilateral perisylvian syndrome". picture of unilateral widening and verti- calisation of the sylvian fossa associated with an abnormal ipsilateral perisylvian Patients and methods cortex. Six patients were studied between 1990 and Results-All children had reduced hemi- 1994. In five patients, MRI was performed at sphere size and thalamostriatal hypopla- 0-5 or 1-5 Tesla, with TI spin echo sequences sia ipsilateral to the cleft and hemiplegia. (TR from 400 to 650 ms, TE from 10 to 40 Cognitive development was mostly ms), T2 spin echo sequences (TR from 1500 impaired. Epilepsy occurred in two to 4000 ms, late TE from 70 to 120 ms) in patients and was mainly characterised by axial, sagittal, or coronal sections. Two chil- partial seizures. Studies with EEG dren underwent studies with Ti weighted showed hemispheric slowing of back- inversion recovery sequences (TR from 1500 ground activity homolateral to the peri- to 2500 ms, TE = 20 ms, TI from 600 to sylvian dysplasia. Occurrence of the 1000 ms). CT was performed in four patients. malformation among their siblings was All patients fulfilled the following radiological not found. criteria: (a) On one side, presence of a sulcus Conclusion-Similar brain malforma- with the location and shape of a sylvian fossa, tions occasionally reported in older but oversized, and extended vertically as patients confirm the clinical picture, spo- shown by the prolongation of the fissure on radic occurrence, and prognosis found, axial sections, at the top of the lateral ventricle allowing the validation of a unilateral and above; (b) absence of visible communica- perisylvian syndrome. tion between the fissure and the ventricle; (c) http://jnnp.bmj.com/ abnormal appearance of the ipsilateral perisyl- (3 Neurol Neurosurg Psychiatsy 1996;61:52-56) vian brain parenchyma. Other investigations included EEG studies and developmental screen by the Denver developmental screening Keywords: cerebral palsy; perisylvian dysplasia test. Karyotyping was performed by standard techniques.

Advances in neuroimaging and especially in on September 25, 2021 by guest. Protected copyright. MRI have allowed the recognition of diffuse as Departement de Results Pediatrie: Service de well as localised disorganisation of cortical Neurologie architecture. Correlations between radiological Mean age at the time of the study was 18 G Sebire patterns and clinical features have led to better (range 9 to 30) months. Consanguinity or A Dusser such as bilateral clinical evidence of occurrence of the malfor- M Tardieu characterisation of disorders P Landrieu perisylvian syndrome,' 2"double cortex" syn- mation among other siblings were not found Service de Radiologie drome,'4 classic agyria-, and atypi- (mean sibship: three (range one to seven chil- B Husson cal lissencephaly.' dren). Pregnancy was seriously disturbed at 15 Service d'Explorations Fonctionelles Neurologiques Hopital Table 1 Clinical aspects of uniilateral perisylvian dysplasia Bicetre, Le Kremlin Bicere, Paris, France Coginitve Seizures Y Navelet Age Motor developmnenit Skuill Sex Conltrol Other Correspondence to: Patielnt ('months) imlpairient DQ(") Speech Tvpe grozthz Dr G Sebire, Service de 1 22 F* RH* 100 Normal Normal -- Neurologie, Departement de 2 20 M* LH* 50 Delayed Spasms -3 SD Pediatrie, Hopital Bicetre, 78 3 9 F RLH 10 Delayed - Normal Death (9 months) rue du general Leclerc, 94275, Le Kremlin Bicktre Optic dysplasia France. 4 14 M RH 50 Delayed Normal Cedex, 5 14 M LH 100 Normal Partial + Normal Optic dysplasia Received 7 August 1995 6 30 F LH 75 Delayed Normal and in revised form 7 February 1996 *Age at last examination. Accepted 7 February 1996 H = Hemiplegia; L = left; R = right; DQ = developmental quotient. Congenital unilateral perisylvian syndrome: radiological basis and clinical correlations 53

Figure 1 EEG recorded in J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.61.1.52 on 1 July 1996. Downloaded from patient 5 (1 year old) Fp2 C4 shows assymetry of background rhythm, slower on the right side. Spike C4 02 v W\r waves are detected in the 'A right occipital region. Calibration: 1 s, 50,uV. Fp2 T4

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weeks for patient 1 by a car crash causing mul- ipsilateral to the dysplasia (patients 2, 4, and tiple fractures of the legs in the mother. 5, fig 1) or bilateral (patient 3). Pregnancy was normal in the other patients. In patient 3, a chromosome study showed Table 1 summarises the clinical features of 46 XX inv 9 (p11; ql3). the six patients. All the children had hemiplegia Table 2 and figs 2 and 3 show neuroradio- with pyramidal symptoms contralateral to the logical features. The dysplasic sylvian fossa brain defect. Among the three patients older was enlarged, appearing as a deep cleft than 16 months, two had acquired the ability directed toward the lateral ventricle, laterally to walk. Bilateral motor anomalies were opened and vertically extended in the opercular detected only in patient 3, who had a cerebellar region. On axial sections the fissure was hemispheric and vermian hypoplasia in addi- shaped either as a straight line or as a Y, thus tion to perisylvian dysplasia. Cognitive devel- showing partial operculation. All patients, opment was impaired in most patients (four except patient 3, presented with a normal http://jnnp.bmj.com/ patients with a development quotient < 75). structure of the inferior part of the sylvian Two children (patients 3 and 5) were blind fossa. The grey matter surrounding the sylvian with a pallor of both optic discs. Patient 5 also fossa was characterised either by a thick cortical presented a right optic hypoplasia with the ribbon lacking interdigitations between grey disc a quarter of the normal size. Non-neuro- and white matter (patients 1, 2, 4, 5, and 6) or logical associated malformation was detected by a thin cortex with excessive folding of small in patient 1 (heart malformation: ventricular convoluted gyri (patient 3). In all patients the

septal defect). hemisphere ipsilateral to the cleft was smaller on September 25, 2021 by guest. Protected copyright. Epileptic seizures occurred in two patients than the contralateral hemisphere (termed (table 1), in whom EEG showed active bursts hemispheric hypoplasia in table 2). All of spikes, spike waves, and slow waves pre- patients had thalamostriatal hypoplasia. The dominantly over central or occipital areas extent of striatal hypoplasia was variable, homolateral to the dysplasia; Studies with restricted to the putamen in patient 1, moder- EEG in other patients mostly showed hemi- ate in patients 4 and 6, and severe in patients 2, spheric slowing of the background activity 3, and 5 (figs 2 and 3). The brain anomalies

Table 2 Radiological aspects of unilateral perisylvian dysplasia Ipsilateral anomalies Patient Perisylvian Hemispheric Ventricular Contralateral No Location macrogyria hypoplasia hypoplasia widening anomalies Otherfeatures 1 L + + + + - SA 2 R + + + + - - 3 R + + + + - Calcifications, Cerebellar hypoplasia 4 L + + + + - - 5 R + + + - - CCA, SA 6 R + + + + - SA CCA = corpus callosum agenesis; L = left; R = right; SA = septal agenesis. 545Sbire, Husson, Dusser, Navelet, Tardieu, Landrieu J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.61.1.52 on 1 July 1996. Downloaded from

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A Figure 2 MRI ofpatient 5 (3 months old). (A) Coronal section shows enlargement and lack of operculation of the right sylvian fossa which is surrounded by an abnormally thick cortex. The right hemisphere has a reduced size. The septum pellucidum is not visible. The striatum and are hypoplasic on the right side. The left temporal horn is enlarged with a hypoplasic, vertically oriented hippocampus (T2 spin echo weighted image with inversed contrast improving the anatomical analysis and accounting for the unusual dark aspect of CSF and white matter; TR = 4000 ins, TE = 90 ins). (B) and (C) Sagittal sections compare the normal aspect of the left sylvian fissure (B) with the verticalised and extended aspect of the right sylvian fissure (C) (Tl spin echo weighted images).

were unilateral, except in patient 5, who had enlargement of the left temporal horn with a maldeveloped, vertically oriented hippocam-

pus (fig 2A). -i5.V.. 4i .- .'. I hl": 1114I ib http://jnnp.bmj.com/ on September 25, 2021 by guest. Protected copyright. Discussion The six patients displayed a congenital disor- der characterised radiologically by a recognis- able unilateral dysplasia of the sylvian region, and clinically by early hemiplegia, impaired cognitive functions, and inconstant epilepsy. Among the classic, clinically defined varieties of cerebral palsy, the present disorder repre- sents a subset of congenital hemiplegia. Curiously, although congenital hemiplegia is frequent, extensively submitted to cerebral imaging, and usually recognised as being the result of prenatal insults, recent clinical works on the subject have not stressed the relevance of unilateral perisylvian dysplasia.1 However, in one report of 111 patients with congenital hemiplegia studied by CT, nine patients (8%) Figure 3 MRI ofpatient I (1 year old): axial section shows enlargement and only partial operculation of the left had brain malformations called "focal pachy- sylvian fossa (Tl spin echo weighted image). The cortex gyria", seemingly corresponding to unilateral bordering the cleft is abnormally thick and devoid of perisylvian dysplasia. Findings similar to interdigitation with white matter. The left striatum is hypoplasic. those of the present patients have been prefer- Congenital uniilateral perisylvian syndrome: radiological basis and clinical correlations 55

entially included in radiological reports on het- plasic sylvian fossa would be an academic J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.61.1.52 on 1 July 1996. Downloaded from erogeneous groups of brain malformations exercise, as the anatomical rearrangements are referred to as "schizencephaly", "focal gyral mainly dependent on the severity and precocity anomalies", "unilateral opercular neuronal of the pathological process. Moreover, the migration disorder", or "porencephaly"'.8 3 abnormal anatomical morphology of the adja- From these studies, we selected 13 patients in cent cortex, mostly corresponding to polymi- whom radiological features corresponded with crogyria and neuronal depopulation, appears unilateral congenital perisylvian dysplasia very similar in both classic porencephaly and (patients 1 to 5,8 patients 1 and 2,9 patients 9 perisylvian dysplasia.' 14 Other lesions such as and 12,10 patients 12 and 18,"1 patients 10 and thalamic hypoplasia and septal agenesis also 1 1,12). Clinical features, such as motor disabil- appear often in classic porencephaly.' "4 '' On ity and intellectual performance, were very the other hand, alterations in gyral develop- close to those of our patients. One half of these ment, indicated by abnormal cortical ribbon patients had hemiplegia. Forty per cent had on imaging, distinguish perisylvian dysplasia normal intelligence. Three patients had bor- from encephaloclastic lesions originating dur- derline performances with IQ between 80 and ing the terminal phase of pregnancy or during 87. The remaining four patients had mental postnatal life such as perinatal stroke or cystic impairment not evaluated by psychometric lesion from perinatal haematoma, which tests. Interestingly, partial epilepsy was the destroy cortical tissue without altering gyral sole manifestation of unilateral perisylvian dys- development. plasia in three patients. Ninety two per cent Cause and timing of the pathological mech- had epilepsy, mainly characterised by partial anisms leading to hemispheric clefts or to peri- seizures, a proportion higher than in our sylvian dysplasia remain controversial. study. Explanations could come from both Previous major hypotheses were either a recruitment bias and from differences in fol- localised disturbance of neuronal proliferation low up: the mean age of patients at the last or migration,'6 17 or a destructive process investigation in these reports was 20 (range 5 occurring during the last stage or after comple- to 63) years versus 18 (range 9 to 30) months tion of migration-that is, between the third in our study. Optic hypoplasia or blindness and sixth month of gestation.'8 2' A hypothesis were not mentioned but finding such an of a true ontogenic defect of brain develop- anomaly in the present series is probably just a ment seems unlikely. Sporadic occurrence, further indication that septo-optic dysplasia is asymmetry of brain defect, encephaloclastic one possible variant of the encephaloclastic appearance of the microscopic morphology, process occurring in mid-gestation. and reports of cases probably related to casual The unilateral perisylvian dysplasia events make the second hypothesis more con- described here could correspond to the unilat- vincing.2' 2 Cellular death can be induced eral counterpart of the "bilateral perisylvian by multiple causes, from purely accidental syndrome".' In this disorder the radiological to genetic, such as anoxia (vasculopathy, sys- features are very similar but the bilateral temic hypotension, vascular embolism or lesions lead to a special clinical picture domi- thrombosis), haemorrhage, infection, trauma,

nated by suprabulbar signs and more severe and intoxication.23 Direct recording of patho- http://jnnp.bmj.com/ mental retardation and epilepsy. Septo-optic logical events occurring during gestation will dysplasia seems to be more frequent in unilat- be necessary to advance our understanding. eral perisylvian dysplasia. Some cases of bilat- eral perisylvian dysplasia so far reported were We thank L Outin and M Thoma for their excellent assistance. clearly asymmetric,' suggesting a continuum 1 Kuzniecky R, Andermann F, Guernni R and the CBPS between the two . In our experience Multicenter Collaborative Study. Congenital bilateral however, clearly unilateral cases have been as perisylvian syndrome: study of 31 patients. Lancet 1993;

341:608-12. on September 25, 2021 by guest. Protected copyright. numerous as bilateral cases, thus the relative 2 Kuzniecky R, Andermann F, Guerrini R and the CBPS incidence of both syndromes is probably more Multicenter Collaborative Study. The epileptic spectrum in the congenital bilateral perisylvian syndrome. balanced than previously thought. Neurology 1994;44:379-85. Unilateral perisylvian dysplasia seems dif- 3 Palmini A, Andermann F, Aicardi J, et al. Diffuse cortical dysplasia, or the "double cortex" syndrome: the clinical ferent from other defects of the cerebral mantle and epileptic spectrum in 10 patients. Neurology 1991; such as those termed porencephaly according 41:1656-62. 4 Barkovich AJ, Guerrini R, Battaglia G, et al. Band hetero- to Herschtl,"' 5or schizencephaly according to topia: correlation of outcome with magnetic resonance Yakovlev and Wadsworth. 16 1' Both terms cor- imaging parameters. Ann N"eurol 1994;36:609-17. 5 Sebire G, Goutieres F, Tardieu M, Landrieu P, Aicardi J. respond to hemispheric clefts or cavities of Extensive macrogyri and/or no visible gyri: distinct clinical, developmental origin that extend through the electro-encephalographical and genetic features accord- ing to different imaging patterns. Neurology 1995;45: full depth of the hemispheric mantle from the 1105-11. ventricle to the subarachnoid space. Such 6 Aicardi J, ed. Cerebral palsy. In: Diseases of the nervous system in childhood. London: MacKeith Press, 1992: defects are of large size or of small size, either 330-74. spanning the whole cerebral mantle or sepa- 7 Wiklund LM, Uvebrant P, Flodmark 0. Morphology of cerebral lesions in children with congenital hemiplegia. rated from the ventricle by a thin layer of tis- Neuroradiology 1990;32: 179-86. sue with a virtual cleft, the two walls of the 8 Aniskiewicz AS, Frumkin NL, Brady DE, Moore JB, Pera A. Magnetic resonance imaging and neurobehavioral cor- lesion being apposed to form a pia-arachnoid relates in schizencephaly. Arch Neurol 1990;40:911-6. seam.'6 1' The central region is the most typical 9 Ambrosetto G. Treatable partial epilepsy and unilateral opercular neuronal migration disorder. Epilepsia 1993; location of the cleft but the frontal or any 34:604-8. other region can be involved as well.'4 In the 10 Guerrini R, Dravet C, Raybaud C, et al. Epilepsy and focal gyral anomalies detected by MRI: electroclinico-morpho- central region, differentiating a true poren- logical correlations and follow-up. Dev Med Child Neurol cephalic cleft from a deeply enlarged and dys- 1992;34:706-18. 56 Sebire, Husson, Dusser, Navelet, Tardieu, Landrieu

11 Menezes L, Aicardi J, Goutieres F. Absence of the septum Neurol 1946;5: 169-205. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.61.1.52 on 1 July 1996. Downloaded from pellucidum with porencephalia. A neuroradiologic syn- 18 Dekaban A. Large defects in cerebral hemisphere associ- drome with variable clinical expression. Arch Neurol ated with cortical dysgenesis. _7 Neuropathol Exp Neurol 1988;45:542-5. 1965;24:512-30. 12 Barkovich AJ, Kjos BO. Schizencephaly: correlation of clin- 19 Lyon G, Robain 0. Etude comparative des encepha- ical findings with MR characteristics. A3rNR Anm 7 lopathies circulatoires prenatales et paranatales- Neuroradiol 1992;13:85-94. hydranencephalies, porencphalies et encephalopathies 13 Miller GM, Stears JC, Guggenheim MA, Wilkening GN. kystiques de la substance blanche. Acta Neroparhol Schizencephaly: a clinical and CT study. Neurology 1963;9:79-98. 1984;34:997-1001. 20 Levine DN, Fisher MA, Caviness V. Porencephaly with 14 Friede RL, ed. Porencephaly, hydranencephaly, multicystic microgyria, a pathological study. Acta Neuropath 1974; encephalopathy. In: Developmental neuropathology. Berlin: 29:99-113. Springer Verlag, 1991:28-30. 21 Bordarier C, Robain 0, Ponsot G. Bilateral porencephalic 15 Aicardi J, Goutieres F. The syndrome of absence of the defect in a newborn after injection of benzol during preg- septum pellucidum with porencephalies and other devel- nancy. Brail Dev 1991;13:126-9. opmental defects. Neuropediatrics 1981;12:319-29. 22 Dominguez R, Vila-Coro AA, Slopis JM, Bohan TP. Brain 16 Yakovlev PI, Wadsworth RC. Schizencephalies. A study of and ocular abnormalities in infants with in utero expo- the congenital clefts in the cerebral mantle. I. Clefts with sure to cocaine and other street drugs. A3tDC 1991; fused lips. 7 Neuropathol Exp Neurol 1946;5: 116-30. 145:688-95. 17 Yakovlev PI, Wadsworth RC. Schizencephalies. A study of 23 Landrieu P, Lacroix C. Schizencephaly, consequence of a the congenital clefts in the cerebral mantle. II. Clefts with developmental vasculopathy? A clinicopathological and lips separated. 7 Neuropathol Exp report. Clin1 Neuropathol 1994;13:1-5.

Gerstmann's syndrome and Herrmann, Schilder, Kroll, and Lange; the syn- drome found acceptance in the contemporary corpus In the 19th century, there flourished the concept of of neurological teaching, but was later seriously chal- localising organic function to discrete areas or "cen- lenged. tres" in the brain. It was extended to attempts to pro- The entity proclaimed by Gerstmann has been seri- vide accurate localisation for the more problematical ously arraigned, notably by Critchley in a classic and higher cortical and psychological dysfunctions. Of critical review.' He demurred at the idea of an many such syndromes described at the turn of the 20th autonomous, independent syndrome, and at its alleged century, the syndrome of Gerstmann is a good and oft localising value. Benton too, harshly but probably cited example: justly, regarded it: "an artifact of defective and biased "The subject of this paper .. I first described observation having little support for its alleged focal several years ago (1924)' under the name of 'finger diagnostic significance."4 Further, the description was agnosia'. It manifests itself as an isolated distur- not original: Anton (1899) and Hartmann (1902) bance in the recognition, naming, choosing, and dif- described similar cases (though with bilateral pathol- ferential exhibition of the various fingers of both ogy and therefore not strictly comparable). Critchley hands-one's own fingers as well as those of another assigned priority to Jules Badal, ophthalmologist in person.... Furthermore, I will discuss the associa- Bordeaux, who in 1888 accurately reported the essential tion that I noted between this symptom and a dis- features in a patient named Valerie, suffering the post- turbance in right-left orientation (in one's own as eclamptic state.' well as in another's body), agraphia and acalculia. Josef Gerstmann (1887-1969) of Vienna was a pupil ... in some it existed as an independent condi- of the Nobel prize winner Wagner von Jauregg; he

tion from the beginning, while in others-though became professor of neurology and psychiatry and http://jnnp.bmj.com/ seldom it was a residual syndrome after regression director at the Maria-Thereisen-Schlossel. He fled the of a more complex deficit. oncoming Nazi regime in 1938, but continued his ... In its selective form ... , apraxia, work in the United States and wrote several papers on agnosia have been lacking. Furthermore, the other the variation of symptoms, pathology, and the localising signs that have sometimes been associated with the value of his syndrome. syndrome (such as right hemianopsia, diminution of opticokinetic nystagmus, amnestic disturbance of 1 Gerstmann J. Fingeragnosie: Eine umschriebene Storung word-finding, impairment in reading ability,...) der Orientierung am eigenen Korper. Wien klin1 Wschr- can be characterised as neighbouring or bordering 1924;37: 1010-2. on September 25, 2021 by guest. Protected copyright. symptoms because of their variable appearance and 2 Gerstmann J. Zur Symptomatologie der Hirnlasionen im mildness. The phenomenon of finger agnosia itself Ubergangsgebiet der unteren Parietal-und mittleren Occipitalwindung. (Das Syndrom: Fingeragnosie, always appeared as an essential disturbance of Rechts-Links-Storung, Agraphie, Akalkulie). Nerveniarzt recognition and orientation. 1 930;3:69 1-5. ... It has become evident that the syndrome of 3 Critchley M. The enigma of Gerstmann's syndrome. Brain be to a focal 1 966;89: 183-98. finger agnosia, agraphia etc can related 4 Benton AL. The fiction of Gerstmann's syndrome. 7 disturbance in the area of transition between the Neurol Neurosurg Psychiatry 1961;24:176-9. angular and second occipital convolution.... the 5 Badal J. Arch Ophthal (Paris) 1888, 8:97 cited by is caused a unilateral lesion in the Critchley. syndrome by J M S PEARCE left hemisphere in right-handed individuals."2 304 Beverley Road, Anlaby Gerstmann referred to corroborative cases of Potzl Hull HU10 7BG, UK