SEMINARS IN NEUROLOGY-VOLUME
11, N O . 1 MARCH 1991
Neuropathologic Correlates of Learning Disabilities
The phrase "learning disabilities" (LD) refers to a heterogeneous group of disorders characterized by singular difficulties with learning academic materials, usually of one type or just a few types, LD therefore represent a group of disorders that are conceptualized, diagnosed, and treated on thc basis of educational criteria and are not formally viewed in the light of contemporary developmental neuroscience, including child neurology, or developmental cognitive science, including child neuropsychology. Yet, even this academically based diagnosis stipulates in most accepted definitions that the child in question not have generalized mental retardation or other tangible neurologic deficits (including blindness or hearing loss), mental illness, severe contributing motivational factors, or social deprivation. However, the educationally based nosology of LD is a focus of continual debate and revision (for a recent treatment of the problem of definition, the reader is referred to Hammill'), which has the practical effect of either including or excluding large numbers of children from fiscal programs aimed at diagnosis and remediation, but which does not shed any new light on the biologic underpinnings. Thus, it is important to be aware of the fact that any contemporary neurologic approach to the understanding of this group of conditions, including neuroanatomic and imaging studies, must rely on essentially nonbiologic markers. Such approaches have the side effect of leading to biologically inhomogeneous test groups and an unknown number of cryptic cases among control samples. One of the most common and best understood forms of learning disabilities is developmental dyslexia, in which the learning deficit is best demonstrated in written language. Dyslexics show special difficulty learning to read and write, but often they also exhibit milder problems with oral language,
arithmetic, attention, and motor coordination."" As with other forms of LD, dyslexia is also heterog e n e ~ u s which ,~ means that a large number of neurologic studies on dyslexia will need to be done before a clear idea about the range of neuroanatomic substrates can emerge. Thus far, postmortem data are available on brains of 11 dyslexic individuals,j-' nnlne brains were studied in our laboratory, and data from seven have been p~blished.~-" T h e documentation of the dyslexia is not uniform, in either the number or the types of testing instruments used to establish the diagnosis. However, it can be stated with confidence that all of the patients had difficulty with learning to read and achieved a level of reading competence that was far below that expected on the basis of intelligence, motivation, effort, and opportunity. In some but not all of the cases, this level was known to be at least 2 standard deviations below expectation, and in all the diagnosis of dyslexia was made during life by a special education expert. This article will deal with the neuroanatomic findings in the 11 cases of developmental dyslexia in which brain tissue was available fbr examination. In all but one of the cases, all or a substantial portion of the brain was studied at autopsy; in the remaining case, the brain tissue was removed during epilepsy surgery. In addition, 1 will review data from experimental animal models used in this laboratory to investigate various aspects of the neuroanatomic and neuropathologic findings made in the human material.
BRAIN ASYMMETRY The eventual presence of brain change in developmental dyslexia need not signify pathologic
Associate Professor of Neurology (Neuroscience), Department of Neurology, Harvard Medical School and Beth Israel Hospital, Boston, Massachusetts Reprint requests: Dr. Galaburda, 330 Brookline Avenue, Koston, MA 02215 Copyright 0 1991 by Thienie Medical Publishers, Inc., 381 Park Avenue South, New York, NY 10016. All rights reserved.
Downloaded by: Universite Laval. Copyrighted material.
Albert M . Galaburda, M.D.
Figure 1. Line diagram of the plana temporalia (PT), which show the standard pattern of asymmetry. The preponderance of the left side is often severalfold. In the dyslexic specimens, the plana have been consistently symmetrical. HG: Heschl's Gyrus.
bruins studied at autopsy, and increased symmetry"," or reversal of asymmetryN' is found in the imaging studies. Although the distribution of planum asymmetry has not been investigated with respect to handedness, a related asymmetry involving the Sylvian fissure shows a less striking left bias in lefthanders, who instead are symmetrical as often as 50% of the Some of the dyslexic individuals were left-handed. However, even with this under consideration, there is a significant excess of symmetrical plana in dyslexic samples. In the next section I will address the possible significance of symmetry inferred from experimental studies.
ANIMAL STUDIES OF ASYMMETRY For a review of the literature on neuroanatomic asymmetry in nonhuman brains, the reader is referred to Sherman et al." I n general, it may be stated that some cortical and subcortical areas in nonhuman mammals, including rodents, are apt to be asymmetrical with a subset showing symmetry, as is the case in the human planum temporale. O n e difference, which is not relevant to the present argument but which is often raised in discussions, is that among nonhuman animals the magnitude of asymmetry is less and there is a lesser population bias in favor of the left o r the right side. I n other words, in these animals, the left-largers, right-largers, and symmetricals are more evenly distributed in the sample. Thinking phrenologically, it is reasonable to conjecture that the absence of asymmetry in the dyslexic sample means that the usually larger left planum has failed to develop to the appropriate size needed to support linguistic capacity, hence the language disability. Instead, symmetrical brain areas are larger than asymmetrical homologues. Thus, for example, when the planum temporale in the human brain o r the visual o r somesthetic cortices in the rat brain are asymmetrical, there is, respectively, less overall planum, visual cortex, o r somesthetic cortex than when the same areas are symmetrical.'H~'"Furthermore, the presence of symmetry in the planum temporale signifies that the usually smaller right side has grown big and not that the usually larger left side has failed to develop. In other words, dyslexic brains have a n excess, not a deficiency, of the amount of posterior language area. T h e elements of the cortex that might constitute the excess found in the symmetrical cases were analyzed in the rat visual cortex. It was fbund that the large side differs in the number of neurons instead of in the packing density of neuron^.'^
Downloaded by: Universite Laval. Copyrighted material.
change. Indeed, there has long been an interest in the effect of size and shape of parts of the brain on intellectual aptitude and response to injury (the phrenological period), which continues today through studies employing neuroimaging devices. Changes in overall brain size have not charactcrized the brains of dyslexics, although in o u r laboratory particularly the brains of dyslexic males tend to be large (>I500 gm). Deviations from the expected pattern of hemispheric asymmetry of one of the language areas have, however, been a consistent finding in the nine cerebra studied in this laboratoryi-!' and in studies during life by means of computed tomography (CT) o r magnetic resonance imaging (MRI) scans."'-" Neither the case reported by Drake%or that of Levine et alf' provided information about brain asymmetry. T h e cerebral hemispheres in toto tend to be symmetrical in size if not in shape.'Wowever, when specific cortical and subcortical areas are assessed by linear, areal, and volumetric measurements, both grossly and architectonically, asymmetries emerge.I4 One of the best known and replicated of these asymmetries is that of the planum temporale'VFig. 1). This gross anatomic landmark contains several architectonic subdivisions and portions of auditory-related cortexl%nd has been implicated in lesions that can cause Wernickc's aphasia-hence its importance to language function and possibly dyslexia. About two thirds of brains free of pathologic change show linear15," and areallx asymmetry of this structure in favor of the left side. Between 20 and 25% of brains, depending on whether length o r surface area is measured, show no asymmetry, with the remaining brains having asymmetry in favor of the right side. Symmetry is the rule i n the planum temporale of dyslexic
21
22
CEREBROCORTICAL ANOMALIES Although it is interesting to postulate that disturbances in asymmetry of language areas in dyslexics, with their attendant exuberance in ~ieuronal numbers and connectivity, may contribute to the cognitive disorder, the significance of these finclings remains speculative in that very little is known regarding the effect of brain symmetry and asymmetry on cognitive function. Laterality is thought to affect strategies for solving some linguistic tasks,:" and anomalous lateralization, such as that postulated for the dyslexic brain, may lead to the loss of essential strategies for learning to read. Although this is an attractive hypothesis that still needs a great deal of experimental confirmation, it is also part of the anatomic picture of developmental dyslexia that frank neuropathologic changes are present. These will be detailed in this section. Previous to any report on brain findings in dyslexia, there was a report of a case of congenital aphasia, in which bilateral malacia in the perisylvian regions, presumably of perinatal origin, was found."" T h e first case report of brain findings in dyslexia was that of Drake,%hicich specified abnormalities in cortical folding, size of the corpus callosum, and abnormal location of neurons. T h e parietal cortex was abnormally convoluted bilaterally, the cerebral cortex was more massive than normal, the corpus callosum was thin in areas related to that abnormal parietal cortex, and diffusely distributed ectopic neurons were present in the subcortical white matter. T h e patient died of a hemorrhage into an arteriovenous malformation involving the vermis o f t h e cerebellum. A second case was reported by Levirle et a]." 'The brain findings obtained from a left temporal lobectomy specimen consisted of glial scarring and an arteriovenous malformation. No mention was made of cortical anomalies o r subcortical heterotopias, but focal disturbances of cortical architecture are common in association with parenchymal arteriovenous anomalies. O u r laboratory has analyzed and published four male cases of dyslexia studied in whole brain serial sectioi~s'.~ and partial histologic information is available in two additional cases. Also, whole brain histologic data were obtained from three female cases, which have been reported separately." MZCROGYRZA, MZCRODYSGENESZS, AND OTHER ANOMALIES
Two of the male cases exhibited focal microgyria. They consisted of the classic picture of lo-
Downloaded by: Universite Laval. Copyrighted material.
Others have reported asymmetries in cell numbers in subcortical and cortical structures in monkey In other words, dyslexic brains may sufer from having too many neurons in the posterior language areas, specfically the right side. T h e hypothesis thus far would be that the exuberance of neurons in the dyslexic brains is causally related to the cognitive disorder. This represents a departure from standard hypotheses in most neurologic disorders, which instead tend to implicate neuronal poverty o r loss in the causation of symptoms and signs. T h e properties of the brain depend in large part on the number and types of neurons but also on the number and pattern of connections. Abnormalities of connections in developmental disorders, such as strabismus," o r in acquired injury,"-'"' such as callosal disconnection, may lead to neurologic, including behavioral, deficits. We compared callosal connections in rats with symmetrical and asymmetrical visual and somesthetic cortices.'" As suspected on the basis of increased number of neurons, there were increased callosal projections in symmetrical areas. Moreover, the pattern of connections also differed. A larger proportion of symmetrical areas received callosal terrriiriatioris than that in symmetrical areas. 71'herefore it is possible that the posterior language areas i r ~the dyslexic brains are involved in an altered degree and pattern of' interhemispheric communication. T h e developmental timing of the differences between symmetrical and asymmetrical brain areas can only be approximated in the human brain. I n the rodent, neuronal production is virtually complete by the end of gestation, and neuronal migration to the neocortex as well as postmigrational neuronal death continue for a short while after birth. Establishment of' callosal connectivity, which includes pruning and redirection of early-generated axons, goes on during the first 2 postnatal weeks. In the human, production of cortical neurons ends just before the middle of pregnancy, after which neuronal migration and maturation and establishment of connections continue into gestation and the early postnatal period. Most of the experimental evidence would tentatively place the production of symmetrical and asymmetrical cortical areas and their axonal connections in the human mostly within the second half of gestation. Recent work in this laboratory has showed that the determination of neuronal numbers to produce asymmetry o r lack thereof occurs during early growth of the germinal zones rather than during late neuronal proliferation."' It is estimated that developmental factors that alter these relationships with respect to the brain o f t h e dyslexic act mostly during this period.
cally increased folding of the cortex, fused ~nolecular layers, indistinct o r decr-eased lamination, and associated abnormal corticallpial vessels. In one case the microgyria involved auditory areas of' the left hemisphere; in the other no language-relev2int area was affected. All of the male cases and two of the three ftmale cases contained a variable number arid distribution of small areas of cortical dysgenesis, termed micr-odysgenesis (Fig. 2). This finding has been more uriifi)rm than microgyria. T h e rnicrodysgeriesis consisted most often of ectopic nests of neurons and glia in the molecular layer, often accompanied by sut?jacerit, focal disturbances in cortical lamination, intracortical tufts of rnyelinated fibers perpendicular to the pia, and a central 11lood vessel. 'I'he foci varied in riu~nt)er-sfrom :10 to 150 and tended to be lateralized to the left liemisphere; some cases, however, showed a syrrimetrical distribution. Fl'he h c i did riot necessarily involve the posterior language areas, but they c o ~ i sisteritly clustered near the foot of' the inferior frolital gyrus in the vicinity of' the classic Broca's area. I n some cases the tiistribution was I-eminiscent of portions of the vascular borderzorie between the anterior, mitltlle, arid posterior cerebral arteries (Fig. 4).
Downloaded by: Universite Laval. Copyrighted material.
Figure 2. Example of cerebrocortical microdysgenesis. Note the disruption of the pial surface by the wartlike excrescence. There is an associated abnormal vessel and subjacent dysplasia of the cortical laminae.
'Iivo of the three female and one of the male dyslexic brairis showed a different torn1 of histopathologic change, albeit in a similar distribution in the cortex (Fig. 4). l'hese lesions consisted of small diameter intracortical scars (less than 700 p n ) located mostly in the arterial borderzone. O n cell stains there were neuronal loss and gliosis; some hemosiderin accumulation in macrophages; and, occasionally, abnormal blood vessels with either wall thickening o r inflammatory cells. Many of these lesions were myelinated, thus suggesting that the irijury took place some time before the end of the second o r third year of lift."'4 In one of'the fernale cases these cortical scars could be seen in the vicinity of molecular layer ectopias (Fig. 3). An attempt has been ~ n a d eto examine appropriate control brains. This has not been an easy task because available normative specimens usually come from elderly individuals for whom accurate records o r family-derived i11fi)rmation to exclude the presence of a learning disability is absent. Furthermore, reports of control brains in the literature d o not usually include findings in serially sectioned whole specimens, which are the only appropriate controls for the dyslexic cases. We have relied on the serially sectiorleti whole brains from 2 :1
,11/\K(,'H 1991
cases,"Vn contrast to the much larger number in the dyslexic cases. Furthermore, in the control cases with microdysgenesis the planum temporale showed the usual asymmetrical configuration. Many foci of myelinated small scars similar to those of the dyslexic patients were seen in two o f t h e normals." In the latter, however, the frontal portions of the vascular borderzones were not involved, in contrast to the dyslexic cases. We may conclude, although pending confirmation in larger series, that symmetry of the planum temporule and involv~mentoftthe inferior ,frontal
11, N O . 1 MARCH 1991
Neuropathologic Correlates of Learning Disabilities
The phrase "learning disabilities" (LD) refers to a heterogeneous group of disorders characterized by singular difficulties with learning academic materials, usually of one type or just a few types, LD therefore represent a group of disorders that are conceptualized, diagnosed, and treated on thc basis of educational criteria and are not formally viewed in the light of contemporary developmental neuroscience, including child neurology, or developmental cognitive science, including child neuropsychology. Yet, even this academically based diagnosis stipulates in most accepted definitions that the child in question not have generalized mental retardation or other tangible neurologic deficits (including blindness or hearing loss), mental illness, severe contributing motivational factors, or social deprivation. However, the educationally based nosology of LD is a focus of continual debate and revision (for a recent treatment of the problem of definition, the reader is referred to Hammill'), which has the practical effect of either including or excluding large numbers of children from fiscal programs aimed at diagnosis and remediation, but which does not shed any new light on the biologic underpinnings. Thus, it is important to be aware of the fact that any contemporary neurologic approach to the understanding of this group of conditions, including neuroanatomic and imaging studies, must rely on essentially nonbiologic markers. Such approaches have the side effect of leading to biologically inhomogeneous test groups and an unknown number of cryptic cases among control samples. One of the most common and best understood forms of learning disabilities is developmental dyslexia, in which the learning deficit is best demonstrated in written language. Dyslexics show special difficulty learning to read and write, but often they also exhibit milder problems with oral language,
arithmetic, attention, and motor coordination."" As with other forms of LD, dyslexia is also heterog e n e ~ u s which ,~ means that a large number of neurologic studies on dyslexia will need to be done before a clear idea about the range of neuroanatomic substrates can emerge. Thus far, postmortem data are available on brains of 11 dyslexic individuals,j-' nnlne brains were studied in our laboratory, and data from seven have been p~blished.~-" T h e documentation of the dyslexia is not uniform, in either the number or the types of testing instruments used to establish the diagnosis. However, it can be stated with confidence that all of the patients had difficulty with learning to read and achieved a level of reading competence that was far below that expected on the basis of intelligence, motivation, effort, and opportunity. In some but not all of the cases, this level was known to be at least 2 standard deviations below expectation, and in all the diagnosis of dyslexia was made during life by a special education expert. This article will deal with the neuroanatomic findings in the 11 cases of developmental dyslexia in which brain tissue was available fbr examination. In all but one of the cases, all or a substantial portion of the brain was studied at autopsy; in the remaining case, the brain tissue was removed during epilepsy surgery. In addition, 1 will review data from experimental animal models used in this laboratory to investigate various aspects of the neuroanatomic and neuropathologic findings made in the human material.
BRAIN ASYMMETRY The eventual presence of brain change in developmental dyslexia need not signify pathologic
Associate Professor of Neurology (Neuroscience), Department of Neurology, Harvard Medical School and Beth Israel Hospital, Boston, Massachusetts Reprint requests: Dr. Galaburda, 330 Brookline Avenue, Koston, MA 02215 Copyright 0 1991 by Thienie Medical Publishers, Inc., 381 Park Avenue South, New York, NY 10016. All rights reserved.
Downloaded by: Universite Laval. Copyrighted material.
Albert M . Galaburda, M.D.
Figure 1. Line diagram of the plana temporalia (PT), which show the standard pattern of asymmetry. The preponderance of the left side is often severalfold. In the dyslexic specimens, the plana have been consistently symmetrical. HG: Heschl's Gyrus.
bruins studied at autopsy, and increased symmetry"," or reversal of asymmetryN' is found in the imaging studies. Although the distribution of planum asymmetry has not been investigated with respect to handedness, a related asymmetry involving the Sylvian fissure shows a less striking left bias in lefthanders, who instead are symmetrical as often as 50% of the Some of the dyslexic individuals were left-handed. However, even with this under consideration, there is a significant excess of symmetrical plana in dyslexic samples. In the next section I will address the possible significance of symmetry inferred from experimental studies.
ANIMAL STUDIES OF ASYMMETRY For a review of the literature on neuroanatomic asymmetry in nonhuman brains, the reader is referred to Sherman et al." I n general, it may be stated that some cortical and subcortical areas in nonhuman mammals, including rodents, are apt to be asymmetrical with a subset showing symmetry, as is the case in the human planum temporale. O n e difference, which is not relevant to the present argument but which is often raised in discussions, is that among nonhuman animals the magnitude of asymmetry is less and there is a lesser population bias in favor of the left o r the right side. I n other words, in these animals, the left-largers, right-largers, and symmetricals are more evenly distributed in the sample. Thinking phrenologically, it is reasonable to conjecture that the absence of asymmetry in the dyslexic sample means that the usually larger left planum has failed to develop to the appropriate size needed to support linguistic capacity, hence the language disability. Instead, symmetrical brain areas are larger than asymmetrical homologues. Thus, for example, when the planum temporale in the human brain o r the visual o r somesthetic cortices in the rat brain are asymmetrical, there is, respectively, less overall planum, visual cortex, o r somesthetic cortex than when the same areas are symmetrical.'H~'"Furthermore, the presence of symmetry in the planum temporale signifies that the usually smaller right side has grown big and not that the usually larger left side has failed to develop. In other words, dyslexic brains have a n excess, not a deficiency, of the amount of posterior language area. T h e elements of the cortex that might constitute the excess found in the symmetrical cases were analyzed in the rat visual cortex. It was fbund that the large side differs in the number of neurons instead of in the packing density of neuron^.'^
Downloaded by: Universite Laval. Copyrighted material.
change. Indeed, there has long been an interest in the effect of size and shape of parts of the brain on intellectual aptitude and response to injury (the phrenological period), which continues today through studies employing neuroimaging devices. Changes in overall brain size have not charactcrized the brains of dyslexics, although in o u r laboratory particularly the brains of dyslexic males tend to be large (>I500 gm). Deviations from the expected pattern of hemispheric asymmetry of one of the language areas have, however, been a consistent finding in the nine cerebra studied in this laboratoryi-!' and in studies during life by means of computed tomography (CT) o r magnetic resonance imaging (MRI) scans."'-" Neither the case reported by Drake%or that of Levine et alf' provided information about brain asymmetry. T h e cerebral hemispheres in toto tend to be symmetrical in size if not in shape.'Wowever, when specific cortical and subcortical areas are assessed by linear, areal, and volumetric measurements, both grossly and architectonically, asymmetries emerge.I4 One of the best known and replicated of these asymmetries is that of the planum temporale'VFig. 1). This gross anatomic landmark contains several architectonic subdivisions and portions of auditory-related cortexl%nd has been implicated in lesions that can cause Wernickc's aphasia-hence its importance to language function and possibly dyslexia. About two thirds of brains free of pathologic change show linear15," and areallx asymmetry of this structure in favor of the left side. Between 20 and 25% of brains, depending on whether length o r surface area is measured, show no asymmetry, with the remaining brains having asymmetry in favor of the right side. Symmetry is the rule i n the planum temporale of dyslexic
21
22
CEREBROCORTICAL ANOMALIES Although it is interesting to postulate that disturbances in asymmetry of language areas in dyslexics, with their attendant exuberance in ~ieuronal numbers and connectivity, may contribute to the cognitive disorder, the significance of these finclings remains speculative in that very little is known regarding the effect of brain symmetry and asymmetry on cognitive function. Laterality is thought to affect strategies for solving some linguistic tasks,:" and anomalous lateralization, such as that postulated for the dyslexic brain, may lead to the loss of essential strategies for learning to read. Although this is an attractive hypothesis that still needs a great deal of experimental confirmation, it is also part of the anatomic picture of developmental dyslexia that frank neuropathologic changes are present. These will be detailed in this section. Previous to any report on brain findings in dyslexia, there was a report of a case of congenital aphasia, in which bilateral malacia in the perisylvian regions, presumably of perinatal origin, was found."" T h e first case report of brain findings in dyslexia was that of Drake,%hicich specified abnormalities in cortical folding, size of the corpus callosum, and abnormal location of neurons. T h e parietal cortex was abnormally convoluted bilaterally, the cerebral cortex was more massive than normal, the corpus callosum was thin in areas related to that abnormal parietal cortex, and diffusely distributed ectopic neurons were present in the subcortical white matter. T h e patient died of a hemorrhage into an arteriovenous malformation involving the vermis o f t h e cerebellum. A second case was reported by Levirle et a]." 'The brain findings obtained from a left temporal lobectomy specimen consisted of glial scarring and an arteriovenous malformation. No mention was made of cortical anomalies o r subcortical heterotopias, but focal disturbances of cortical architecture are common in association with parenchymal arteriovenous anomalies. O u r laboratory has analyzed and published four male cases of dyslexia studied in whole brain serial sectioi~s'.~ and partial histologic information is available in two additional cases. Also, whole brain histologic data were obtained from three female cases, which have been reported separately." MZCROGYRZA, MZCRODYSGENESZS, AND OTHER ANOMALIES
Two of the male cases exhibited focal microgyria. They consisted of the classic picture of lo-
Downloaded by: Universite Laval. Copyrighted material.
Others have reported asymmetries in cell numbers in subcortical and cortical structures in monkey In other words, dyslexic brains may sufer from having too many neurons in the posterior language areas, specfically the right side. T h e hypothesis thus far would be that the exuberance of neurons in the dyslexic brains is causally related to the cognitive disorder. This represents a departure from standard hypotheses in most neurologic disorders, which instead tend to implicate neuronal poverty o r loss in the causation of symptoms and signs. T h e properties of the brain depend in large part on the number and types of neurons but also on the number and pattern of connections. Abnormalities of connections in developmental disorders, such as strabismus," o r in acquired injury,"-'"' such as callosal disconnection, may lead to neurologic, including behavioral, deficits. We compared callosal connections in rats with symmetrical and asymmetrical visual and somesthetic cortices.'" As suspected on the basis of increased number of neurons, there were increased callosal projections in symmetrical areas. Moreover, the pattern of connections also differed. A larger proportion of symmetrical areas received callosal terrriiriatioris than that in symmetrical areas. 71'herefore it is possible that the posterior language areas i r ~the dyslexic brains are involved in an altered degree and pattern of' interhemispheric communication. T h e developmental timing of the differences between symmetrical and asymmetrical brain areas can only be approximated in the human brain. I n the rodent, neuronal production is virtually complete by the end of gestation, and neuronal migration to the neocortex as well as postmigrational neuronal death continue for a short while after birth. Establishment of' callosal connectivity, which includes pruning and redirection of early-generated axons, goes on during the first 2 postnatal weeks. In the human, production of cortical neurons ends just before the middle of pregnancy, after which neuronal migration and maturation and establishment of connections continue into gestation and the early postnatal period. Most of the experimental evidence would tentatively place the production of symmetrical and asymmetrical cortical areas and their axonal connections in the human mostly within the second half of gestation. Recent work in this laboratory has showed that the determination of neuronal numbers to produce asymmetry o r lack thereof occurs during early growth of the germinal zones rather than during late neuronal proliferation."' It is estimated that developmental factors that alter these relationships with respect to the brain o f t h e dyslexic act mostly during this period.
cally increased folding of the cortex, fused ~nolecular layers, indistinct o r decr-eased lamination, and associated abnormal corticallpial vessels. In one case the microgyria involved auditory areas of' the left hemisphere; in the other no language-relev2int area was affected. All of the male cases and two of the three ftmale cases contained a variable number arid distribution of small areas of cortical dysgenesis, termed micr-odysgenesis (Fig. 2). This finding has been more uriifi)rm than microgyria. T h e rnicrodysgeriesis consisted most often of ectopic nests of neurons and glia in the molecular layer, often accompanied by sut?jacerit, focal disturbances in cortical lamination, intracortical tufts of rnyelinated fibers perpendicular to the pia, and a central 11lood vessel. 'I'he foci varied in riu~nt)er-sfrom :10 to 150 and tended to be lateralized to the left liemisphere; some cases, however, showed a syrrimetrical distribution. Fl'he h c i did riot necessarily involve the posterior language areas, but they c o ~ i sisteritly clustered near the foot of' the inferior frolital gyrus in the vicinity of' the classic Broca's area. I n some cases the tiistribution was I-eminiscent of portions of the vascular borderzorie between the anterior, mitltlle, arid posterior cerebral arteries (Fig. 4).
Downloaded by: Universite Laval. Copyrighted material.
Figure 2. Example of cerebrocortical microdysgenesis. Note the disruption of the pial surface by the wartlike excrescence. There is an associated abnormal vessel and subjacent dysplasia of the cortical laminae.
'Iivo of the three female and one of the male dyslexic brairis showed a different torn1 of histopathologic change, albeit in a similar distribution in the cortex (Fig. 4). l'hese lesions consisted of small diameter intracortical scars (less than 700 p n ) located mostly in the arterial borderzone. O n cell stains there were neuronal loss and gliosis; some hemosiderin accumulation in macrophages; and, occasionally, abnormal blood vessels with either wall thickening o r inflammatory cells. Many of these lesions were myelinated, thus suggesting that the irijury took place some time before the end of the second o r third year of lift."'4 In one of'the fernale cases these cortical scars could be seen in the vicinity of molecular layer ectopias (Fig. 3). An attempt has been ~ n a d eto examine appropriate control brains. This has not been an easy task because available normative specimens usually come from elderly individuals for whom accurate records o r family-derived i11fi)rmation to exclude the presence of a learning disability is absent. Furthermore, reports of control brains in the literature d o not usually include findings in serially sectioned whole specimens, which are the only appropriate controls for the dyslexic cases. We have relied on the serially sectiorleti whole brains from 2 :1
,11/\K(,'H 1991
cases,"Vn contrast to the much larger number in the dyslexic cases. Furthermore, in the control cases with microdysgenesis the planum temporale showed the usual asymmetrical configuration. Many foci of myelinated small scars similar to those of the dyslexic patients were seen in two o f t h e normals." In the latter, however, the frontal portions of the vascular borderzones were not involved, in contrast to the dyslexic cases. We may conclude, although pending confirmation in larger series, that symmetry of the planum temporule and involv~mentoftthe inferior ,frontal
