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Lesion size and location in recovery from aphasia
ABSTRACT 5ssion she and Iofason are ixqm%ant factors in tJiHmd*tage rwvary. Ikeieov&ry of negative correhition with the exceptio2~ of #~p~~~~ wE& at times shows no correIation or even positive cormiation with lesion size. The patients with hxrgt: lesions, having global or severe BMW’s aphasia, often show a greater improvement of comprehension and patients with smaller lesions, such as anemia, already Me good comprehension, therefore, the c&ing effect lowers the recovery rate. Therefore, large iesions with more recovery and small lesions with less recovery may give rise to a positive correktio~. On the o&e-r hand, there is high negative con-&ion betIesion size sod final outcome. Lesion facation in Broca’s aphasics iodkated that the inferior frontal gyms aad the insula were invohred with both recovered and persisting groups, but the central and supramarginai gyri were usually invoked in cases of poor recovery. Subcortical lesions producing Broca’s aphasia usually have good prognosis. In Wemicke’s aphasia the most consistently involved structure was tht: superior temporal gyros, but in the case of poor recovery, the middle temporal gyms and supramargi~l gyros were si~~dy more ir~voked. Very iarge ksioas involvkg much of the left hemisphere resuft in Me recovery.
ratesshow a trend
Human brain damage, due w s&&e or tmm;l, pr&um de&z&s that recover in two stages. The first stage is related to recovery from the acute effect; of hemorrhage, cellular reaction and chemical alterations. Our interest has: focused on &xond-stage rwovery that takes place months, even years, after injury. The study of recovery from brain timage is more than just a practical, prqnc&ic exercise for the c~~~~~ or a baseline fur therapy. It ah4o provides an Ernest theoretical framework for cerebra1 ~~ga~~ti~~. Monakow’s (1914) expkmation for second-stage x~overy was c&d “diaschisis”” and this is still a valid concept in neurobiology, He thought that in acute injury the damaged brain deprives the surrounding, mostly functionally
50
Joan4 of Nap
VoIunw 3, Number 1 (1988)
connected areas from atrophic influence at innervation causing the initial deficit to be larger than it would have been expected from the original injury; subsequently, these areas recover by acquiring innervation from somewhere else or becoming autonomously functional. Much of what we know about the reorgani~tion of brain function in man comes from the functional analysis of deficits and their relationship to brain lesions. After stroke trauma or infection, human cognition is affected in a complex fashion. The reproducibility of observations is influenced by many biological and psychological factors. The main areas investigated are language, nonverbal cognition, visuomotor performance, and memory. The complexity of deficit analysis in cognition and in aphasia has been recognized and some quantitation has been achieved by several advances in methodology. Firstly, aphasia tests became better standardized and more specific for a language disordered population (Kertesz 1979, 1982; Goodglass and Kaplan 1983). Secondly, the methods of follow-up and the statistical evaluation of change have become more sophisticated. Thirdly, advances in cognitive psychology and linguistics contributed to deficit analysis. Fourthly, neuroimaging allowed us to measure and localize lesions in viva. In this presentation, I am going to describe the main factors in recovery from aphasic deficits . Among the factors important in recovery is initial severity. Early investigators considered initial severity to have a highly predictive value (Godfrey and Douglass 1959; Schuell et al. 1964; Sands et al. 1969; Samo et al. 1970a, b; Cloning et al. 1976; Kertesz and McCabe 1977). The severity of deficit of onset has a considerable effect on comparing recovery rates because mildly affected aphasics do not have much room for recovery (a “ceiling effect”) and severe aphasics often have more potential. Treated patients tend to be selected from the less severe groups and bias the results. Unless initial severity is considered a major factor to be controlled, studies of treatment should not be considered reliable. There are various methods of controlling for initial severity; such as analysis of covariance or using outcome measures instead of recovery rates or the change expressed as percentage of initial severity. The methodology of patient selection is also an important issue. Often patients are entered into recovery studies at various stages on the recovery curve. In our recent studies, we took care to start our evaluation within the acute period, usually between 10 and 45 days after a stroke. Since most of our patients were examined at exactly 14 days after post-onset, this ~pulation is rather homogenous. Only the more severely affected patients, who could not be examined at that time because of intercurrent medical illness or obtundation, were kept until the upper limit of the time period.
Various etiologies were lumped together in many early studies, but this seems a significant disadvantage. Traumatic aphasia, for instance, recovers quickly if it is related to closed head injury. Persisting dysarthria however is common in severe trauma and this often disrupts ~~~i~tion to such a degree that the extent of ~st-t~~atic aphasia is ditBcuh to determine. Penetrating head injury affects a different age group and behaves differently because of the variation in the speed and path of the missiles and the associated concussion. Therefore post-traumatic aphasia is biologically different from the vascular type. There are many similarities, however, indicating that the recurring patterns of aphasic types are not necessarily related to the ~st~bution of vascular lesions. A recent study by Ludlow et al. (1986) on Vietnam Veterans, showed that the lesions that produce persisting asyntactic or Broca’s aphasia are large and involve subcortical structures and the parietal area in addition to Broca’s area, very much the same conclusion that is reached studying stroke recovery. Age or sex does not seem to be a significant factor as long as an adult population with strokes is studied. Prepubertal children recover quite well from injury and even infantile hemispherectomies develop normal speech with only slight limitation on verbal intelligence (Dennis and Kohn 1975). Etiology compounds the age factor since young individuals are much less likely to suffer from stroke. If the factor of etiology is considered carefully, the differences between children and adults in the rate of recovery tends to disappear. Lesion size and location have also been recognized as relevant but complex factors. Until recently, clinicians relied on autopsy correlations but modem neuroimaging has provided an opportunity to study lesion characteristics in vim We presented our first study of lesion size measured on compute~z~ tomography (CT) and recovery from aphasia in 1979 (Kertesz et al. 1979). We found that the larger the lesion the poorer the outcome; in other words, outcome correlated negatively with lesion size. Recovery rates also showed a trend of negative correlation with one unexpected exception. The recovery rate of comp~hension was found to be correlated positively with lesion size! Why this should be, can be best understood if we look at another study of ours in which the best recovered modality was found to be comprehension (Lomas and Kertesz 1978). Patients with large lesions having global or severe Broca’s aphasia, often show greater improvement in comprehension, and patients with smaller lesions, such as anomies, already have good comprehension, therefore they have less room for recovery (a ceiling effect). The large lesions with more recovery and small lesions with little change give rise to a consistently positive correlation unless the initial severity is covaried as was done in our subsequent studies.
52
Journal of Newolingtdsljcs, Volmm 3, Number l(1988)
Since then, various other publications emerged dealing with localization of the lesions in a somewhat different, symptom-oriented approach (Selnes et al. 1983; Knopman et al. 1983). Knopman et al. (1983) looked at lesion size and location and found that in the language area about 60 cm2 was a critical mass, and a larger lesion results in relatively less recovery. They also found that recovery of naming was as good as fluency. They concluded that both pre- and post-central structures are probably needed to maintain fluency. Motor speech has less redundancy and if the surrounding areas are involved, less recovery will take place. Semantic access is severely impaired in Wernicke’s aphasics and in large lesions this recovers less. The symptom-oriented approach generally leads to less focal localization of functional deficits as some of these functions are widely distributed in the brain. Improvement in imaging techniques and in measuring the lesion parameters increased the accuracy of the studies. Most of these rely on CT scan to provide anatomical information. Recently Magnetic Resonance Imaging (MRI) is providing greater white and grey matter contrast and the ability to see the brain in quasi-anatomical sections in any desired plane in viva. The CT scans were somewhat variable with the initial scanning performed with early EM1 instruments but later the acquisition of more up-to-date scanners, such as the GE 8800 and GE 9800 improved the accuracy of lesion sizing and lesion location. Radioisotope scans were also used to confirm localization or to determine the nature of the lesion. Lesion tracing should be performed blindly without knowledge of the patient’s clinical features to avoid bias in locating the anatomical structures that are involved. The issue of direct tracing of lesions or using templates onto which the lesions are drawn cannot be resolved easily. Direct tracing is more reproducible between two observers but because of the variability between head positioning different scanning techniques and the different skull shapes of individuals, tracing on standard templates by a human observer allows mental adjustment for angulation of the head and various differences in the size and shape of the scans of different patients. The digitization of the lesion areas is a fairly standard process and newer scanners have algorithms which provide for an automated pixel count. Even for automatic pixel counts, the human observer has to draw the edges or limits of the lesion. When a lesion is digitized for each slice then the areas can be multiplied by the slice thickness and the volumetric measurement can be obtained. Lesion location is often determined by a check-list of the regions of interest which has been worked out in several laboratories (Selnes et al. 1983; Ludlow et al. 1986) including ours (see below). Most of these regions of interest are similar, except some select areas of equal volume, while others select each with
LedonShemdLocatienbRecoveryfrom~
53
a presumed physiological or cognitive function. The actual involvement in each structure is scored as a percentage of involvement but this is difficult to reproduce and may create a spurious source of variability. A simplified scoring system of less than half, more than half, or total involvement is more realistic.
LANGUAGE AND COGNITIVE MEASURES Various recovery studies used different language examinations. Extremely detailed testing of function does not allow a practical number of follow-up studies. We used the Western Aphasia Battery (WAB) because it covers language functions comprehensively, yet it is practical to administer to most patients, within an hour as far as the oral subtests are concerned (Kertesz 1982). The inter-rater reliability, intratest validity and rationale of the test have been described in detail (Kertesz 1979). It also provides a summary of the language subscores as a measure of overall severity called the aphasia quotient (AQ). Among the subtests, the information content provides a measure of functional communication and it can also be used separately as a measure of recovery. Comprehension is tested with yes-no questions, a pointing task of auditory word recognition, and a syntactically complex sentence comprehension task. Naming of visually presented common objects, sentence completion and responsive speech are measures of lexical access. Repetition is tested with words and sentences of increasing difficulty. The test includes reading, writing and an assessment of praxis, calculation and a section of nonverbal performance, such as Block Design, Raven’s Colored Progressive Matrices (RCPM), drawing and line bisection. The tests were done at 10-45 days, three months, six months and twelve months after stroke. The test has been recently translated and standardized in Japanese and published by Igaku-Shoin. Second stage recovery is more significant in the first 3 months, and recovery curves are initially steeper in all groups and also for the total group. More severely affected aphasics continue to recover at a later stage if they are followed for a sufficient length of time. Some investigators, such as Broida (1977) suggested that recovery continues beyond one year, although this was based on a few selected cases only. In our previous study (Kertesz and McCabe 1977), we found no significant recovery beyond one year when a larger population was looked at. Individual cases, nevertheless, continued to show some improvement beyond one year and certain individual factors, such as environmental stimulation or therapy should not be discounted, as ineffective in a more chronic stage. The recovery scores of writing are of special interest because of the relatively low scores of writing at the onset of an aphasic disturbance. Writing
54
Journal of Neurolinguicrties, Voltme 3, Nm~ber 1(19&I)
appears to be more severely affected and the overall recovery of writing is less than the recovery of oral language function. It is of interest, however, that even anemic aphasics who start at a rather low level show considerable recovery in this group.
LESION SIZE AND RECOVERY
We studied lesion size and recovery in the O-3 month interval in 82 patients in whom unilateral lesions were available on the CT scans for tracing and localization. The analysis was performed for recovery rates, as well as rates controlled for initial severity by using an analysis of covariance. When initial severity is not corrected, a significant positive correlation is obtained for lesion size and performance on yes-no questions, word discrimination tasks, and total comprehension at a .05 level. Raven’s matrices also showed positive correlation at less than .05. When the analysis was performed controlling for initial severity, significant negative correlations were obtained between lesion size and fluency, yes-no questions, sequential commands, repetition, naming, word fluency, sentence completion, drawing and block design tasks. The only correlations not significant were word discrimination, total comprehension and RCPM. Lesion size and 1Zmonth recovery rates were examined in 82 patients. Fifty-eight were also subjects in the O-3 recovery group but the others did not have a 3-month examination. The correlation of lesion size with recovery at 12 months showed slight positive correlation for word finding and writing. Negative correlations were obtained throughout when initial severity was controlled for. These correlations were particularly high for fluency and they were low in the comprehension tasks. Outcome and lesion size, as measured by the last evaluation at 12 months, correlated negatively in a highly significant fashion throughout with lesion size. The recovery of Broca’s and Wernicke’s groups was examined in further detail as they represent important clinical syndromes with double dissociation of functional deficits and variable behaviour on recovery. The recovery of Broca’s aphasics was correlated with lesion size, age, the degree of atrophy, initial severity, and the initial subtests of spontaneous speech, fluency, comprehension, repetition and naming, and the RCPM as a measure of nonverbal performance in each of the follow-up intervals. The most significant correlations were obtained in the outcome measures which showed a negative correlation for lesion size and positive correlation with most other initial language scores. Cerebral atrophy as measured by the ratio of frontal horn width and brain diameter on the horizontal section at the level of the pineal did not correlate significantly.
Leai~~SizeudLocatiaoinRecoveryfromA~
55
Wernicke’s aphasics showed variable recovery. Six patients remained severely affected, and 10 recovered to either anemic or conduction aphasia. The AQ changes were correlated with lesion size, age, initial severity, individual language parameters and RCPM as a nonverbal control test. The results indicate a significant negative correlation between lesion size and recovery, and less than significant correlation for age and outcome. Because of the relatively small number of patients in the Wernicke’s group, a nonparametric comparison of unrecovered, Wernicke’s aphasics with those who recovered completely or towards anemic or conduction aphasia was carried out. The more persistent Wernicke’s aphasics appeared to be slightly older but the difference was not statistically significant. The initial severity was a major factor with the recovering patients being milder to begin with. The lesion size also showed a trend of larger lesions in the persistent group but was not as significant. The possible interaction of cerebral asymmetry or atypically distributed language in the two hemispheres and recovery was explored by Broca’s and Wemicke’s aphasics by measuring the frontal and occipital petalias (prominence of one side or the other) and width on CT scans, according to the methodology of LeMay and Kido (1978). There have been suggestions in the literature that more bilaterally distributed language capacity could result in better recovery in unilateral brain damage (Pieniadz et al. 1983). The “petalias” and width measurements were divided into groups of right larger than left, equal, or left larger than right. Broca’s aphasics were then grouped according to their recovery. Those who remained Broca’s aphasics were compared to those who changed into other categories such as anomies, conduction or transcortical motor aphasia, or recovered completely. Those patients who showed better recovery were in the majority (n = 16). Although there were some trends for the better recovered patients to have less typical cerebral asymmetry with cerebral petalia and width measures, the differences between the two groups were not significant on a chi-square analysis. A similar lack of significance for asymmetries was found in Wernicke’s aphasics. We also split our global group into good and poor recovery taking care to match lesion size. The results of occipital width and protuberance and frontal width and protuberance measurements (see Kertesz et al. 1986 for methodology) are negative. In none of the patients groups could we find a convincing difference in asymmetry pattern between those who recover and those who do not.
LESION LOCATION AND RECOVERY
The CT scan evaluation of lesion locations, using a O-3 point rating of the extent of involvement of each anatomical structure was carried out in 22 Broca’s
56
Journalof Neurolhgdstiq Vdme 3, Nuder 1(1=)
aphasics divided at the median for poor and good recovery. The structures with significant involvement (more than 50X) were the inferior frontal gyrus, especially the pars opercularis and triangularis and the insula in both groups. There were only two patients in whom the posterior inferior frontal gyms was not involved, and all of these patients had significant involvement of the putamen or the caudate nucleus, or both. The difference between the persisting cases of Broca’s aphasia and those which show good recovery was most prominent in the involvement of the pre-central, post-central and supr~ar~nal gyri in the cases of poor recovery. Supramarginal, angular and superior temporal gyri were not involved in those cases where recovery was good. The subcortical regions showed significant differences in the involvement of the putamen and the caudate which was twice as frequent in the persistent cases, while the internal capsule and the central white matter (the corona radiata) was involved equally frequently. Specific structural correlates of recovery were also examined for Wemicke’s aphasia. The individuals were ranked and divided at the median according to the rate of recovery. Those who have better recovery rates have clearly smaller mean lesion volumes and certain structures are less frequently involved, than others. Of the 16 patients who were check-listed, and divided for good recovery and poor recovery status, the most consistently involved structure was the superior temporal gyrus. In cases of poor recovery, the middle temporal gyrus and the supramarginal gyrus are significantly more frequently involved, in addition to the post-central gyrus and the insula which is twice as frequently involved in the unrecovered cases. Involvement of frontal regions is rarely significant. Subcortical structures are also relatively infrequently involved in the unrecovered group. DISCUSSION
A complex interaction of size and location of lesions in addition to time from onset, etiology and initial severity are the main factors in the recovery of cognitive and language loss. Other biological factors such as age, sex and handedness play a less significant role in this rather homogenous stroke population. Rather than anatomical reorgani~tion through axonal regrowth or collateral sprouting that can be demonstrated in the peripheral nervous system, and to a lesser extent in the CNS of animals, such as the rat, probably a functional reorganization underlies recovery in the human brain. Parts of the intact and functionally connected brain substitute for others, and the homologous portion of the contralateral hemisphere may do this to a variable extent but far from completely. Right hemisphere ~om~nsation has been suggested by
LedonSizeandLaathinReuwwyfromAphada
57
Wemicke, himself, and subsequently Henschen (1920-1922) in his large monographs of aphasic and other types of cortical functional deficits. This principle was based on largely anecdotal evidence of large left hemisphere lesions with good recovery. Some patients who became aphasic with a single left hemisphere stroke, and subsequently recover, a second right hemisphere stroke may produce language deficit (Levine and Mohr 1979). These cases are rarely documented and may represent bilateral language organization to begin with, rather than a common mechanism of functional transfer to the contralateral hemispheres after destruction of a certain amount of language related structure in the left hemisphere. One of the most dramatic demonstrations of the residual capacities of the right hemisphere to compensate for the loss of language resulting from left hemisphere lesions’ are the hemispherectomy studies (Smith 1966) which indicated that a picture resembling global aphasia occurs after a left hemispherectomy. Some comprehension recovers but the patient continues to remain nonfluent with only a single word or stereotypical utterances or automatisms. When written or verbal input was separated to each of the hemispheres, it has been demonstrated that the right hemisphere is capable of processing single words, usually concrete nouns (Zaidel 1976). The idea that compensation after a partial left hemisphere damage occurs through right hemisphere functions were supported to some extent by studies of sodium amytal given to aphasics who have recovered (Mempel et al. 1963; Kinsbourne 1971; Czopf 1972). The studies indicated that even though the aphasic disturbance occurred from a left hemisphere lesion it was the right hemispheric injection that increased the language disturbance, indicating that the right hemisphere compensated for the previously occurred deficit produced by the left side. Recent studies of cerebral blood flow with xenon 133 also indicated a right hemisphere participation in recovery to a various degree (Knopman et al. 1984). Positron emission tomography (PET) studies of cerebral metabolism show a great deal of hypometabolism surrounding, and even remote from cerebral infarcts and this also suggested that homologous areas in the opposite hemisphere play a role in compensation (Metter et al. 1981). Our studies, nevertheless, demonstrated the importance of structures that surround the lesion areas in the recovery process. Those left hemisphere structures that are connected sequentially with the opercular and anterior insular regions play a crucial role in recovery from Broca’s aphasia. The results clearly show that patients who have adjacent involvement, especially the inferior portion of the pre-central gyrus and the anterior parietal region, have less recovery than those who spare these areas which probably play a role in recovery.
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JoumdofN eurdineuis3ies, Volume 3, Nmber 1 (l!XB)
In Wernicke’s aphasia the second temporal gyrus, the insular region, and the supramarginal gyrus that surround the superior temporal area must be instrumental in recovery. Damage to these areas result in persisting Wernicke’s syndrome. Larger posterior lesions may destroy access to a potential right hemisphere lexicon (Selnes et al. 1983). Certain aspects of hemispheric specialization may vary according to individuals even though anatomical asymmetries do not seem to play a role in recovery as was suggested. It could be that anatomical asymmetries, as we see them, relate more to handedness variable than language distribution, as suggested by some of our studies in normals (Kertesz et al. 1986) and this is why we are not seeing an effect on language recovery. The individual variations in the intra- and interhemispheric distribution of various functional components may contribute to an important extent to the ability of the mature brain to compensate after a single nonprogressive lesion. Other pathological variations, such as repeated stroke insults, cerebral atrophy, intercurrent latent dementia, etc, remain factors to be considered or even studied directly although they were controlled by exclusion in our study. Lesion size is undoubtedly the most significant factor in the extent of recovery. However, the important exceptions are certain crucial areas in the left hemisphere that are more important for prognosis than others. Motor and premotor phonemic assembly mechanisms are elaborated by a corticalsubcortical network that can be damaged partially with good recovery. However, if both cortical and subcortical components of the network are impaired, recovery is much less likely. This complex integration of various structures also takes place for the processing of language comprehension, although interhemispheric connections may be playing a larger role in comprehension than in motor output. It seems that a restricted deficit in the dominant hemisphere auditory association area, the posterior superior temporal gyrus and the planum temporale can be compensated for by the opposite or homologous hemispheric structures or by surrounding structures in the temporal and inferior parietal regions and in the insula. However, when either of these compensating structures are affected, or when the lesion is large, precluding right hemisphere access, recovery is not likely.
REFERENCES
Broida, H. 1977 “Language Therapy Effects in Long Term Aphasia,” Physical Medicine and Rehabilitation 58, 248-253.
Archives of
Czopf, J. 1972
“Role of the Non~omin~t Hemisphere in the Restitution of Speech in Aphasia,” Archiv fur Psychiarrie und Nerven~r~~iten 216, 162-171. Dennis, M. and B. Kohn 1975 “Comprehension of Syntax in Infantile Hemiplegics After Cerebral Hemid~o~i~tion: Left Hemisphere Superiority, ” Bruin and Language 2,472-482. Gloning, K., R. Trappl, W.D. Heiss, and R. Quatember 1976 Prognosis and Speech Therapy in Aphasia in Neurolinguistics. 4. Recovery in Aphasics, Amsterdam: Swets & Zeitlinger, B.V. Godfrey, CM. and E. Douglass 1959 “The Recovery Process in Aphasia,” C~~ian medical Assoc~tion Journal 80, 618624. Goodglass, H. and E. Kaplan 1983 Boston Naming Test, Philadelphia: Lea and Febiger. Henschen, S.E. 1920 Klinische und Anato~~c~e Beitrage zur Pathol~gie des Gehirns, Vols. 5-7, Stockholm: Nordiska Bokhandel. Kertesz, A. 1979 Aphasia and Associated Disorders, New York: Grune and Stratton. 1982 The Western Aphasia Battery, New York: Grune and Stratton. Kertesz, A., S.E. Black, M. Polk, and J. Howell 1986 “Cerebral Asymmetries on Magnetic Resonance Imaging.” Cortex 22, 117-127. Kertmz, A., W. Harlock, and R. Coates 1979 “Computer Tomographic Localization, Lesion Size and Prognosis in Aphasia,” Brain and Languuge 8, 34-50. Kertesz, A. and P. McCabe 1977 “Recovery Patterns and Prognosis in Aphasia,” Brain 100, l-18. Kinsbourne, M. 1971 “The Minor Cerebral Hemisphere as a Source of Aphasic Speech,” Archives of Neurology 25, 302-306. Knopman, D.S., A.B. Rubens, O.A. Selnes, A.C. Klassen, and M.W. Meyer 1984 “Mechanisms of Recovery from Aphasia: Evidence from Serial Xenon 133 Cerebral Blood Flow Studies,” Annals of Neurology 15.6, 530-535. Knopman, D.S., O.A. Seines, N. Niccum, and A.R. Rubens 1983 “A Lon~tudinal Study of Speech Fluency in Aphasia: CT Scan
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Joumal of Nemolingu&tks, Voltme3, Numberl(1988)
Correlates of Recovery and Persistent Nonfluency,” Neurology 33, 1170-l 178. Lemay, M. and D.K. Kido 1978 “Asymmetries of the Cerebral Hemispheres on Computed Tomograms,” Journal of Computerized Assistant Tomography 2, 471-476. Levine, D.M. and J.P. Mohr 1979 “Language after Bilateral Cerebral Infarctions: Role of the Minor Hemisphere,” Neurology 29, 927-938. Lomas, J. and A. Kertesz 1978 “Patterns of Spontaneous Recovery in Aphasic Groups: A Study of Adult Stroke Patients,” Brain and Language 5, 388-401. Ludlow, C., J. Rosenberg, C. Fair, D. Buck et al. 1986 “Brain Lesions Associated with Nonfluent Aphasia Fifteen Years Following Penetrating Head Injury,” Brain, 109, 55-80. Mempel, E., J. Srebrezynska, J. Subszynskas, and S. Zarski 1963 “Compensation of Speech Disorders by the Non-dominant Cerebral Hemisphere in Adults ,” Journal of Neurology, Neurosurgery and Psychiatry 26, 96.
Metter, E.J., C.G. Wasterlain, D.E. Kuhl, W.R. Hanson, and M.E. Phelps 1981 “FGD Positron Emission Computed Tomography in a Study of Aphasia,” Annals of Neurology 10, 173-183. Monakow, C. von 1914 Die Lokalisation im Grosshirn und der Abbau der Funktionen Durch Corticale Herde, Bergmann: Wiesbaden. Pieniadz, J.M., M.A. Naeser, E. Koff, and H.L. Levine 1983 “CT Scan Cerebral Hemispheric Asymmetry Measurements in Stroke Cases with Global Aphasia: Atypical Asymmetries Associated with Improved Recovery,“Cortex 19, 371-393. Sands, E., M.T. Sat-no, and D. Shankweiler 1969 “Long-term Assessment of Language Function in Aphasia Due to Stroke,” Archives of Physical Medicine and Rehabilitation SO, 202-222.
Sarno, M.T., M. Silverman, and E. Levita 1970 “Psychosocial Factors and Recovery in Geriatric Patients with Severe Aphasia,” Journal of American Geriatric Society 18,405-409.
1970 “Speech Therapy
and Language
Recovery
in Severe Aphasia,”
Journal of Speech and Hearing Research 13, 607-623.
Schuell, A., J.J. Jenkins, and J. Pabon 1964 Aphasia in Adults, New York: Harper Row
Lesion Size and Lwation in Recovery from Apbmda
61
Selnes, O.A., D.S. Knopman, N. Niccum, and A.B. Rubens 1983 “CT Scan Correlates of Auditory Comprehension Deficits in Aphasia: A Prospective Recovery Study,” Annals of Neurology 13, 558-566. Smith, A. 1966 “Speech and Other Functions after Left (Dominant) Hemispherectomy,” Journal of Neurology, Neurosurgery and Psychiatry 29, 467-47 1.
Zaidel, E. 1976
“Auditory Vocabulary in the Right Hemisphere Following Brain Bisection or Hemidecortication,” Cortex 12, 191-211.
ratesshow a trend
Human brain damage, due w s&&e or tmm;l, pr&um de&z&s that recover in two stages. The first stage is related to recovery from the acute effect; of hemorrhage, cellular reaction and chemical alterations. Our interest has: focused on &xond-stage rwovery that takes place months, even years, after injury. The study of recovery from brain timage is more than just a practical, prqnc&ic exercise for the c~~~~~ or a baseline fur therapy. It ah4o provides an Ernest theoretical framework for cerebra1 ~~ga~~ti~~. Monakow’s (1914) expkmation for second-stage x~overy was c&d “diaschisis”” and this is still a valid concept in neurobiology, He thought that in acute injury the damaged brain deprives the surrounding, mostly functionally
50
Joan4 of Nap
VoIunw 3, Number 1 (1988)
connected areas from atrophic influence at innervation causing the initial deficit to be larger than it would have been expected from the original injury; subsequently, these areas recover by acquiring innervation from somewhere else or becoming autonomously functional. Much of what we know about the reorgani~tion of brain function in man comes from the functional analysis of deficits and their relationship to brain lesions. After stroke trauma or infection, human cognition is affected in a complex fashion. The reproducibility of observations is influenced by many biological and psychological factors. The main areas investigated are language, nonverbal cognition, visuomotor performance, and memory. The complexity of deficit analysis in cognition and in aphasia has been recognized and some quantitation has been achieved by several advances in methodology. Firstly, aphasia tests became better standardized and more specific for a language disordered population (Kertesz 1979, 1982; Goodglass and Kaplan 1983). Secondly, the methods of follow-up and the statistical evaluation of change have become more sophisticated. Thirdly, advances in cognitive psychology and linguistics contributed to deficit analysis. Fourthly, neuroimaging allowed us to measure and localize lesions in viva. In this presentation, I am going to describe the main factors in recovery from aphasic deficits . Among the factors important in recovery is initial severity. Early investigators considered initial severity to have a highly predictive value (Godfrey and Douglass 1959; Schuell et al. 1964; Sands et al. 1969; Samo et al. 1970a, b; Cloning et al. 1976; Kertesz and McCabe 1977). The severity of deficit of onset has a considerable effect on comparing recovery rates because mildly affected aphasics do not have much room for recovery (a “ceiling effect”) and severe aphasics often have more potential. Treated patients tend to be selected from the less severe groups and bias the results. Unless initial severity is considered a major factor to be controlled, studies of treatment should not be considered reliable. There are various methods of controlling for initial severity; such as analysis of covariance or using outcome measures instead of recovery rates or the change expressed as percentage of initial severity. The methodology of patient selection is also an important issue. Often patients are entered into recovery studies at various stages on the recovery curve. In our recent studies, we took care to start our evaluation within the acute period, usually between 10 and 45 days after a stroke. Since most of our patients were examined at exactly 14 days after post-onset, this ~pulation is rather homogenous. Only the more severely affected patients, who could not be examined at that time because of intercurrent medical illness or obtundation, were kept until the upper limit of the time period.
Various etiologies were lumped together in many early studies, but this seems a significant disadvantage. Traumatic aphasia, for instance, recovers quickly if it is related to closed head injury. Persisting dysarthria however is common in severe trauma and this often disrupts ~~~i~tion to such a degree that the extent of ~st-t~~atic aphasia is ditBcuh to determine. Penetrating head injury affects a different age group and behaves differently because of the variation in the speed and path of the missiles and the associated concussion. Therefore post-traumatic aphasia is biologically different from the vascular type. There are many similarities, however, indicating that the recurring patterns of aphasic types are not necessarily related to the ~st~bution of vascular lesions. A recent study by Ludlow et al. (1986) on Vietnam Veterans, showed that the lesions that produce persisting asyntactic or Broca’s aphasia are large and involve subcortical structures and the parietal area in addition to Broca’s area, very much the same conclusion that is reached studying stroke recovery. Age or sex does not seem to be a significant factor as long as an adult population with strokes is studied. Prepubertal children recover quite well from injury and even infantile hemispherectomies develop normal speech with only slight limitation on verbal intelligence (Dennis and Kohn 1975). Etiology compounds the age factor since young individuals are much less likely to suffer from stroke. If the factor of etiology is considered carefully, the differences between children and adults in the rate of recovery tends to disappear. Lesion size and location have also been recognized as relevant but complex factors. Until recently, clinicians relied on autopsy correlations but modem neuroimaging has provided an opportunity to study lesion characteristics in vim We presented our first study of lesion size measured on compute~z~ tomography (CT) and recovery from aphasia in 1979 (Kertesz et al. 1979). We found that the larger the lesion the poorer the outcome; in other words, outcome correlated negatively with lesion size. Recovery rates also showed a trend of negative correlation with one unexpected exception. The recovery rate of comp~hension was found to be correlated positively with lesion size! Why this should be, can be best understood if we look at another study of ours in which the best recovered modality was found to be comprehension (Lomas and Kertesz 1978). Patients with large lesions having global or severe Broca’s aphasia, often show greater improvement in comprehension, and patients with smaller lesions, such as anomies, already have good comprehension, therefore they have less room for recovery (a ceiling effect). The large lesions with more recovery and small lesions with little change give rise to a consistently positive correlation unless the initial severity is covaried as was done in our subsequent studies.
52
Journal of Newolingtdsljcs, Volmm 3, Number l(1988)
Since then, various other publications emerged dealing with localization of the lesions in a somewhat different, symptom-oriented approach (Selnes et al. 1983; Knopman et al. 1983). Knopman et al. (1983) looked at lesion size and location and found that in the language area about 60 cm2 was a critical mass, and a larger lesion results in relatively less recovery. They also found that recovery of naming was as good as fluency. They concluded that both pre- and post-central structures are probably needed to maintain fluency. Motor speech has less redundancy and if the surrounding areas are involved, less recovery will take place. Semantic access is severely impaired in Wernicke’s aphasics and in large lesions this recovers less. The symptom-oriented approach generally leads to less focal localization of functional deficits as some of these functions are widely distributed in the brain. Improvement in imaging techniques and in measuring the lesion parameters increased the accuracy of the studies. Most of these rely on CT scan to provide anatomical information. Recently Magnetic Resonance Imaging (MRI) is providing greater white and grey matter contrast and the ability to see the brain in quasi-anatomical sections in any desired plane in viva. The CT scans were somewhat variable with the initial scanning performed with early EM1 instruments but later the acquisition of more up-to-date scanners, such as the GE 8800 and GE 9800 improved the accuracy of lesion sizing and lesion location. Radioisotope scans were also used to confirm localization or to determine the nature of the lesion. Lesion tracing should be performed blindly without knowledge of the patient’s clinical features to avoid bias in locating the anatomical structures that are involved. The issue of direct tracing of lesions or using templates onto which the lesions are drawn cannot be resolved easily. Direct tracing is more reproducible between two observers but because of the variability between head positioning different scanning techniques and the different skull shapes of individuals, tracing on standard templates by a human observer allows mental adjustment for angulation of the head and various differences in the size and shape of the scans of different patients. The digitization of the lesion areas is a fairly standard process and newer scanners have algorithms which provide for an automated pixel count. Even for automatic pixel counts, the human observer has to draw the edges or limits of the lesion. When a lesion is digitized for each slice then the areas can be multiplied by the slice thickness and the volumetric measurement can be obtained. Lesion location is often determined by a check-list of the regions of interest which has been worked out in several laboratories (Selnes et al. 1983; Ludlow et al. 1986) including ours (see below). Most of these regions of interest are similar, except some select areas of equal volume, while others select each with
LedonShemdLocatienbRecoveryfrom~
53
a presumed physiological or cognitive function. The actual involvement in each structure is scored as a percentage of involvement but this is difficult to reproduce and may create a spurious source of variability. A simplified scoring system of less than half, more than half, or total involvement is more realistic.
LANGUAGE AND COGNITIVE MEASURES Various recovery studies used different language examinations. Extremely detailed testing of function does not allow a practical number of follow-up studies. We used the Western Aphasia Battery (WAB) because it covers language functions comprehensively, yet it is practical to administer to most patients, within an hour as far as the oral subtests are concerned (Kertesz 1982). The inter-rater reliability, intratest validity and rationale of the test have been described in detail (Kertesz 1979). It also provides a summary of the language subscores as a measure of overall severity called the aphasia quotient (AQ). Among the subtests, the information content provides a measure of functional communication and it can also be used separately as a measure of recovery. Comprehension is tested with yes-no questions, a pointing task of auditory word recognition, and a syntactically complex sentence comprehension task. Naming of visually presented common objects, sentence completion and responsive speech are measures of lexical access. Repetition is tested with words and sentences of increasing difficulty. The test includes reading, writing and an assessment of praxis, calculation and a section of nonverbal performance, such as Block Design, Raven’s Colored Progressive Matrices (RCPM), drawing and line bisection. The tests were done at 10-45 days, three months, six months and twelve months after stroke. The test has been recently translated and standardized in Japanese and published by Igaku-Shoin. Second stage recovery is more significant in the first 3 months, and recovery curves are initially steeper in all groups and also for the total group. More severely affected aphasics continue to recover at a later stage if they are followed for a sufficient length of time. Some investigators, such as Broida (1977) suggested that recovery continues beyond one year, although this was based on a few selected cases only. In our previous study (Kertesz and McCabe 1977), we found no significant recovery beyond one year when a larger population was looked at. Individual cases, nevertheless, continued to show some improvement beyond one year and certain individual factors, such as environmental stimulation or therapy should not be discounted, as ineffective in a more chronic stage. The recovery scores of writing are of special interest because of the relatively low scores of writing at the onset of an aphasic disturbance. Writing
54
Journal of Neurolinguicrties, Voltme 3, Nm~ber 1(19&I)
appears to be more severely affected and the overall recovery of writing is less than the recovery of oral language function. It is of interest, however, that even anemic aphasics who start at a rather low level show considerable recovery in this group.
LESION SIZE AND RECOVERY
We studied lesion size and recovery in the O-3 month interval in 82 patients in whom unilateral lesions were available on the CT scans for tracing and localization. The analysis was performed for recovery rates, as well as rates controlled for initial severity by using an analysis of covariance. When initial severity is not corrected, a significant positive correlation is obtained for lesion size and performance on yes-no questions, word discrimination tasks, and total comprehension at a .05 level. Raven’s matrices also showed positive correlation at less than .05. When the analysis was performed controlling for initial severity, significant negative correlations were obtained between lesion size and fluency, yes-no questions, sequential commands, repetition, naming, word fluency, sentence completion, drawing and block design tasks. The only correlations not significant were word discrimination, total comprehension and RCPM. Lesion size and 1Zmonth recovery rates were examined in 82 patients. Fifty-eight were also subjects in the O-3 recovery group but the others did not have a 3-month examination. The correlation of lesion size with recovery at 12 months showed slight positive correlation for word finding and writing. Negative correlations were obtained throughout when initial severity was controlled for. These correlations were particularly high for fluency and they were low in the comprehension tasks. Outcome and lesion size, as measured by the last evaluation at 12 months, correlated negatively in a highly significant fashion throughout with lesion size. The recovery of Broca’s and Wernicke’s groups was examined in further detail as they represent important clinical syndromes with double dissociation of functional deficits and variable behaviour on recovery. The recovery of Broca’s aphasics was correlated with lesion size, age, the degree of atrophy, initial severity, and the initial subtests of spontaneous speech, fluency, comprehension, repetition and naming, and the RCPM as a measure of nonverbal performance in each of the follow-up intervals. The most significant correlations were obtained in the outcome measures which showed a negative correlation for lesion size and positive correlation with most other initial language scores. Cerebral atrophy as measured by the ratio of frontal horn width and brain diameter on the horizontal section at the level of the pineal did not correlate significantly.
Leai~~SizeudLocatiaoinRecoveryfromA~
55
Wernicke’s aphasics showed variable recovery. Six patients remained severely affected, and 10 recovered to either anemic or conduction aphasia. The AQ changes were correlated with lesion size, age, initial severity, individual language parameters and RCPM as a nonverbal control test. The results indicate a significant negative correlation between lesion size and recovery, and less than significant correlation for age and outcome. Because of the relatively small number of patients in the Wernicke’s group, a nonparametric comparison of unrecovered, Wernicke’s aphasics with those who recovered completely or towards anemic or conduction aphasia was carried out. The more persistent Wernicke’s aphasics appeared to be slightly older but the difference was not statistically significant. The initial severity was a major factor with the recovering patients being milder to begin with. The lesion size also showed a trend of larger lesions in the persistent group but was not as significant. The possible interaction of cerebral asymmetry or atypically distributed language in the two hemispheres and recovery was explored by Broca’s and Wemicke’s aphasics by measuring the frontal and occipital petalias (prominence of one side or the other) and width on CT scans, according to the methodology of LeMay and Kido (1978). There have been suggestions in the literature that more bilaterally distributed language capacity could result in better recovery in unilateral brain damage (Pieniadz et al. 1983). The “petalias” and width measurements were divided into groups of right larger than left, equal, or left larger than right. Broca’s aphasics were then grouped according to their recovery. Those who remained Broca’s aphasics were compared to those who changed into other categories such as anomies, conduction or transcortical motor aphasia, or recovered completely. Those patients who showed better recovery were in the majority (n = 16). Although there were some trends for the better recovered patients to have less typical cerebral asymmetry with cerebral petalia and width measures, the differences between the two groups were not significant on a chi-square analysis. A similar lack of significance for asymmetries was found in Wernicke’s aphasics. We also split our global group into good and poor recovery taking care to match lesion size. The results of occipital width and protuberance and frontal width and protuberance measurements (see Kertesz et al. 1986 for methodology) are negative. In none of the patients groups could we find a convincing difference in asymmetry pattern between those who recover and those who do not.
LESION LOCATION AND RECOVERY
The CT scan evaluation of lesion locations, using a O-3 point rating of the extent of involvement of each anatomical structure was carried out in 22 Broca’s
56
Journalof Neurolhgdstiq Vdme 3, Nuder 1(1=)
aphasics divided at the median for poor and good recovery. The structures with significant involvement (more than 50X) were the inferior frontal gyrus, especially the pars opercularis and triangularis and the insula in both groups. There were only two patients in whom the posterior inferior frontal gyms was not involved, and all of these patients had significant involvement of the putamen or the caudate nucleus, or both. The difference between the persisting cases of Broca’s aphasia and those which show good recovery was most prominent in the involvement of the pre-central, post-central and supr~ar~nal gyri in the cases of poor recovery. Supramarginal, angular and superior temporal gyri were not involved in those cases where recovery was good. The subcortical regions showed significant differences in the involvement of the putamen and the caudate which was twice as frequent in the persistent cases, while the internal capsule and the central white matter (the corona radiata) was involved equally frequently. Specific structural correlates of recovery were also examined for Wemicke’s aphasia. The individuals were ranked and divided at the median according to the rate of recovery. Those who have better recovery rates have clearly smaller mean lesion volumes and certain structures are less frequently involved, than others. Of the 16 patients who were check-listed, and divided for good recovery and poor recovery status, the most consistently involved structure was the superior temporal gyrus. In cases of poor recovery, the middle temporal gyrus and the supramarginal gyrus are significantly more frequently involved, in addition to the post-central gyrus and the insula which is twice as frequently involved in the unrecovered cases. Involvement of frontal regions is rarely significant. Subcortical structures are also relatively infrequently involved in the unrecovered group. DISCUSSION
A complex interaction of size and location of lesions in addition to time from onset, etiology and initial severity are the main factors in the recovery of cognitive and language loss. Other biological factors such as age, sex and handedness play a less significant role in this rather homogenous stroke population. Rather than anatomical reorgani~tion through axonal regrowth or collateral sprouting that can be demonstrated in the peripheral nervous system, and to a lesser extent in the CNS of animals, such as the rat, probably a functional reorganization underlies recovery in the human brain. Parts of the intact and functionally connected brain substitute for others, and the homologous portion of the contralateral hemisphere may do this to a variable extent but far from completely. Right hemisphere ~om~nsation has been suggested by
LedonSizeandLaathinReuwwyfromAphada
57
Wemicke, himself, and subsequently Henschen (1920-1922) in his large monographs of aphasic and other types of cortical functional deficits. This principle was based on largely anecdotal evidence of large left hemisphere lesions with good recovery. Some patients who became aphasic with a single left hemisphere stroke, and subsequently recover, a second right hemisphere stroke may produce language deficit (Levine and Mohr 1979). These cases are rarely documented and may represent bilateral language organization to begin with, rather than a common mechanism of functional transfer to the contralateral hemispheres after destruction of a certain amount of language related structure in the left hemisphere. One of the most dramatic demonstrations of the residual capacities of the right hemisphere to compensate for the loss of language resulting from left hemisphere lesions’ are the hemispherectomy studies (Smith 1966) which indicated that a picture resembling global aphasia occurs after a left hemispherectomy. Some comprehension recovers but the patient continues to remain nonfluent with only a single word or stereotypical utterances or automatisms. When written or verbal input was separated to each of the hemispheres, it has been demonstrated that the right hemisphere is capable of processing single words, usually concrete nouns (Zaidel 1976). The idea that compensation after a partial left hemisphere damage occurs through right hemisphere functions were supported to some extent by studies of sodium amytal given to aphasics who have recovered (Mempel et al. 1963; Kinsbourne 1971; Czopf 1972). The studies indicated that even though the aphasic disturbance occurred from a left hemisphere lesion it was the right hemispheric injection that increased the language disturbance, indicating that the right hemisphere compensated for the previously occurred deficit produced by the left side. Recent studies of cerebral blood flow with xenon 133 also indicated a right hemisphere participation in recovery to a various degree (Knopman et al. 1984). Positron emission tomography (PET) studies of cerebral metabolism show a great deal of hypometabolism surrounding, and even remote from cerebral infarcts and this also suggested that homologous areas in the opposite hemisphere play a role in compensation (Metter et al. 1981). Our studies, nevertheless, demonstrated the importance of structures that surround the lesion areas in the recovery process. Those left hemisphere structures that are connected sequentially with the opercular and anterior insular regions play a crucial role in recovery from Broca’s aphasia. The results clearly show that patients who have adjacent involvement, especially the inferior portion of the pre-central gyrus and the anterior parietal region, have less recovery than those who spare these areas which probably play a role in recovery.
58
JoumdofN eurdineuis3ies, Volume 3, Nmber 1 (l!XB)
In Wernicke’s aphasia the second temporal gyrus, the insular region, and the supramarginal gyrus that surround the superior temporal area must be instrumental in recovery. Damage to these areas result in persisting Wernicke’s syndrome. Larger posterior lesions may destroy access to a potential right hemisphere lexicon (Selnes et al. 1983). Certain aspects of hemispheric specialization may vary according to individuals even though anatomical asymmetries do not seem to play a role in recovery as was suggested. It could be that anatomical asymmetries, as we see them, relate more to handedness variable than language distribution, as suggested by some of our studies in normals (Kertesz et al. 1986) and this is why we are not seeing an effect on language recovery. The individual variations in the intra- and interhemispheric distribution of various functional components may contribute to an important extent to the ability of the mature brain to compensate after a single nonprogressive lesion. Other pathological variations, such as repeated stroke insults, cerebral atrophy, intercurrent latent dementia, etc, remain factors to be considered or even studied directly although they were controlled by exclusion in our study. Lesion size is undoubtedly the most significant factor in the extent of recovery. However, the important exceptions are certain crucial areas in the left hemisphere that are more important for prognosis than others. Motor and premotor phonemic assembly mechanisms are elaborated by a corticalsubcortical network that can be damaged partially with good recovery. However, if both cortical and subcortical components of the network are impaired, recovery is much less likely. This complex integration of various structures also takes place for the processing of language comprehension, although interhemispheric connections may be playing a larger role in comprehension than in motor output. It seems that a restricted deficit in the dominant hemisphere auditory association area, the posterior superior temporal gyrus and the planum temporale can be compensated for by the opposite or homologous hemispheric structures or by surrounding structures in the temporal and inferior parietal regions and in the insula. However, when either of these compensating structures are affected, or when the lesion is large, precluding right hemisphere access, recovery is not likely.
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