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Isolated Retrograde Amnesia: Different Etiologies, Same Mechanisms?
NOTE ISOLATED RETROGRADE AMNESIA: DIFFERENT ETIOLOGIES, SAME MECHANISMS? 1 Elkhonon Goldberg, James E.O. Hughes, Steven Mattis and Sanford P. Autin (Downstate Medical Center of SUNY, St. Luke's-Roosevelt Medical Center, Montefiore Hospital and Harbor CAT Scan, Neurology Center, New York)
Roman-Campos, Poser and Wood (1980) reported a case of transient global amnesia (TGA) accompanied by a recent memory deficit and retrograde amnesia 10 years deep. The episode resolved itself in a virtually complete recovery from the recent memory deficit but the patient was left with persistent retrograde amnesia more than 5 years deep. On re-evaluation one year after the TGA episode, the retrograde amnesia was still present but no deficit of recent memory was observed. The neurological examination was unremarkable; repeated EEG studies revealed theta activity arising from the left temporal area; CT scan and brain scan examinations were negative. The authors point out that the case is extremely unusual in that ordinarily complete recovery of remote memory takes place following TGA episodes, with the exception of the memory for events which occurred during a limited period of time during and surrounding the attack. Also, the general finding of a persistent retrograde amnesia unaccompanied by an appreciable anterograde amnesia is highly unusual in itself. On the basis of the EEG findings, the patient's performance on motor tests and occasional neologisms, the authors conclude that a mild left temporal dysfunction is present, possibly a unilateral infarction of the medial aspect of the left temporal lobe. The authors point out, however, that the lesion sustained by the patient must have been "more extensive than that which produces transient global amnesia in order to account for the persistent retrograde memory deficit" (p. 517), and that the possibility of lesions other than or in addition to the left temporal one cannot be discounted. The authors raise the intriguing issue of the mechanisms of an isolated retrograde amnesia. 1 A comment on the report by G. Roman-Campos, C.M. Poser and F.B. Wood, "Persistent retrograde memory deficit after transient global amnesia."
Cortex (1982) 18, 459-462
460
Elkhonon Goldberg, James E.O. Hughes, Steven Mattis and Sanford P. Antin
A post-head trauma case with profound and relatively isolated retrograde amnesia was recently reported by Goldberg et al. (1981). As in the case described by Roman-Campos et al., there was an initial picture of profound anterograde and profound retrograde amnesia. Over a period of two years, there was considerable recovery from anterograde amnesia as measured both by clinical observations and formal tests. By the end of the two-year period, the deficit of recent memory ceased to be a limiting factor in real life situations for the patient, and was considerably reduced, albeit still present on formal tests. The patient's Wechsler Memory Quotient recovered during this period in parallel with his WAIS IQ; both reached the normal range and were mutually consistent. Remote memory deficits, on the other hand, did not show any improvement either with respect to general or personal knowledge, as measured either by formal tests or clinical observations. Two years after the accident leading to the head trauma, the patient still had massive retrograde amnesia spanning about 20 years back. The two cases are similar also in that motor and intellectual skills (e.g. driving, tennis playing, reading, spelling, computations) were intact; chronological border between the period of lucid memories and that of amnesia was fuzzy; and some isolated recognition of names or faces was occasionally observed even with respect to the years for which massive retrograde amnesia was obvious. In the case ·described by Goldberg et al., CT scan examinations revealed bilateral temporal involvement, moderate dilation of the ventricular system and a tegmental mesencephalic lesion extending from the ventral tegmental portion of the upper mesencephalon caudally to the ventral portion of the ponto-mesencephalic junction. In the latter area, reticular nuclei and pathways are found which project to and receive projections from the limbic structures most often implicated in memory: mammillary bodies and hippocampi (Shute and Lewis, 1967; Moore and Bloom, 1979). It was proposed by Goldberg et al. that the interruption of the reticular projections due to the tegmental lesion was responsible for the relatively isolated retrograde amnesia observed in the patient. The rationale behind the hypothesis was the assumption that selective phasic activation of the aforementioned limbic structures is a critical component in the mechanisms of long-term retrieval. Although the etiologies are entirely different in the two cases described, the cognitive phenomenology is quite similar, and the question naturally arises whether similar mechanisms are behind them. Roma'nCampos et al. point out in their discussion that "in the majority of cases of TGA, a bilateral transitory ischemia of the hippocampus has been postulated" (p. 516), due to deficient circulation either in the anterior choroidal artery or the vertebrobasilar system territories. Both arterial systems
Isolated Retrograde Amnesia
461
provide blood supply to hippocampi and both of them are involved with blood supply to the mesencephalic and pontine areas where reticular nuclei are found. Anterior choroidal artery supplies the hippocampal formation and large portions of the posterior limb of the internal capsule where frontopontine and cortico-reticular fibers are found (Carpenter, 1976). The vertebral basilar system is the source of blood supply for the medial surface of the temporal lobes and to virtually entire pons and mesencephalon including tegmentum (Carpenter, 1976). It is possible that the anterior choroidal and/ or vertebrobasilar insufficiency can lead both to bilateral hippocampal ischemia thus producing a TGA attack, and to some permanent damage to mesencephalic and/ or pontine structures, e.g. infarction thus producing a lesion similar to the one described by Goldberg et al. Given the size of mesencephalic tegmentum, the density of wiring within it, and its being the "bottleneck" for ventrally distributed reticular pathways, it is quite conceivable that a very small lesion in that area can have profound cognitive consequences. The same applies to ventral pontine structures. The tegmental mesencephalic area of hypodensity described by Goldberg et al. was small, such that it could not be revealed by CT scan examinations using 8 mm thickness of cuts; it could be revealed, however, when 5 mm thickness was used. The study by Goldberg et al. was conducted in 1979, three years after Ramon-Campos et al. examined their patient (in 1976). The maximum resolution of CT scanners available in 1976 hardly exceeded 10 mm thickness. It is probable that a CT scan re-examination, using finer resolution which became available with the arrival of recent generations of CT scanners, would shed further light on the mechanisms responsible for memory deficits in the extremely interesting patient described by Roman-Campos et aLit is possible that it would reveal a mesencephalic or (less likely) pontine lesion in the region where it would be likely to destroy reticular nuclei or pathways. Given that the degree of differentiation of reticular projections increases upward along the neural axis and is greater in the mesencephalon than in the pons (Carpenter, 1976) one can expect on a priori grounds that isolated retrograde amnesia would follow mesencephalic tegmental rather than ventral pontine damage. The latter, on the other hand, would be more likely to produce a more generalized deficit involving arousal. Cases of isolated persistent retrograde amnesia are quite rare but not unheard of. It is possible that such cases share not only common cognitive symptomatology but also common neural mechanisms. If this is the case, then a new, distinct neurological and neuropsychological syndrome may
462
Elkhonon Goldberg, James E.O. Hughes, Steven Mattis and Sanford P. Antin
be emerging. The tegmental mesencephalic hypothesis formulated by Goldberg et al, was an attempt to define such mechanisms as a step toward describing this syndrome. Given the rarity of an isolated retrograde amnesia unaccompanied by a comparably severe anterograde amnesia or general arousal deficit, every case is of considerable interest. Further, careful studies of instances of this intriguing condition may contribute in important ways both to theoretical neuroscience and to clinical neurological and neuropsychological taxonomy. ABSTRACT
Two cases of persistent retrograde amnesia are compared. Although etiologies are different (head trauma and transient global amnesia sequelae), it is possible that mechanisms are the same: impairment of selective reticulo-limbic interactions due to brain-stem damage. REFERENCES CARPENTER, M.D. (1976) Human Neuroanatomy, Williams and Wilkins, Baltimore. GOLDBERG, E., ANTIN, S.P., BILDER, R.M., GERSTMAN, L.J. HUGHES, J.E.O., and MATTIS, S. ( 1981) Retrograde amnesia: Possible role of mesencephalic reticular activation in long-term memory, Science, 213, 1392-1394. MOORE, R.Y., and BLOOM, F.E. (1979) Central catecholacemic neuron systems. Anatomy and physiology of the norepinephrine and epinephrine systems, Ann. Rev. Neurosci., 2,
113-168.
ROMAN-CAMPOS, G., POSER, C.M., and WooD, F. (1980) Persistent retrograde memory deficit after transient global amnesia, Cortex, 16, 509-518. SHUTE, D.D.C., and LEWIS, P.R. (1967) The ascending cholinergic reticular system. Neocortical, olfactory and subcortical projections, Brain, 90, 497-520. Elkhonon Goldberg, P.O. Box 88, Department of Psychiatry, Downstate Medical Center of SUNY, 450 Clarkson Avenue, Brooklyn, N.Y. 11203
Roman-Campos, Poser and Wood (1980) reported a case of transient global amnesia (TGA) accompanied by a recent memory deficit and retrograde amnesia 10 years deep. The episode resolved itself in a virtually complete recovery from the recent memory deficit but the patient was left with persistent retrograde amnesia more than 5 years deep. On re-evaluation one year after the TGA episode, the retrograde amnesia was still present but no deficit of recent memory was observed. The neurological examination was unremarkable; repeated EEG studies revealed theta activity arising from the left temporal area; CT scan and brain scan examinations were negative. The authors point out that the case is extremely unusual in that ordinarily complete recovery of remote memory takes place following TGA episodes, with the exception of the memory for events which occurred during a limited period of time during and surrounding the attack. Also, the general finding of a persistent retrograde amnesia unaccompanied by an appreciable anterograde amnesia is highly unusual in itself. On the basis of the EEG findings, the patient's performance on motor tests and occasional neologisms, the authors conclude that a mild left temporal dysfunction is present, possibly a unilateral infarction of the medial aspect of the left temporal lobe. The authors point out, however, that the lesion sustained by the patient must have been "more extensive than that which produces transient global amnesia in order to account for the persistent retrograde memory deficit" (p. 517), and that the possibility of lesions other than or in addition to the left temporal one cannot be discounted. The authors raise the intriguing issue of the mechanisms of an isolated retrograde amnesia. 1 A comment on the report by G. Roman-Campos, C.M. Poser and F.B. Wood, "Persistent retrograde memory deficit after transient global amnesia."
Cortex (1982) 18, 459-462
460
Elkhonon Goldberg, James E.O. Hughes, Steven Mattis and Sanford P. Antin
A post-head trauma case with profound and relatively isolated retrograde amnesia was recently reported by Goldberg et al. (1981). As in the case described by Roman-Campos et al., there was an initial picture of profound anterograde and profound retrograde amnesia. Over a period of two years, there was considerable recovery from anterograde amnesia as measured both by clinical observations and formal tests. By the end of the two-year period, the deficit of recent memory ceased to be a limiting factor in real life situations for the patient, and was considerably reduced, albeit still present on formal tests. The patient's Wechsler Memory Quotient recovered during this period in parallel with his WAIS IQ; both reached the normal range and were mutually consistent. Remote memory deficits, on the other hand, did not show any improvement either with respect to general or personal knowledge, as measured either by formal tests or clinical observations. Two years after the accident leading to the head trauma, the patient still had massive retrograde amnesia spanning about 20 years back. The two cases are similar also in that motor and intellectual skills (e.g. driving, tennis playing, reading, spelling, computations) were intact; chronological border between the period of lucid memories and that of amnesia was fuzzy; and some isolated recognition of names or faces was occasionally observed even with respect to the years for which massive retrograde amnesia was obvious. In the case ·described by Goldberg et al., CT scan examinations revealed bilateral temporal involvement, moderate dilation of the ventricular system and a tegmental mesencephalic lesion extending from the ventral tegmental portion of the upper mesencephalon caudally to the ventral portion of the ponto-mesencephalic junction. In the latter area, reticular nuclei and pathways are found which project to and receive projections from the limbic structures most often implicated in memory: mammillary bodies and hippocampi (Shute and Lewis, 1967; Moore and Bloom, 1979). It was proposed by Goldberg et al. that the interruption of the reticular projections due to the tegmental lesion was responsible for the relatively isolated retrograde amnesia observed in the patient. The rationale behind the hypothesis was the assumption that selective phasic activation of the aforementioned limbic structures is a critical component in the mechanisms of long-term retrieval. Although the etiologies are entirely different in the two cases described, the cognitive phenomenology is quite similar, and the question naturally arises whether similar mechanisms are behind them. Roma'nCampos et al. point out in their discussion that "in the majority of cases of TGA, a bilateral transitory ischemia of the hippocampus has been postulated" (p. 516), due to deficient circulation either in the anterior choroidal artery or the vertebrobasilar system territories. Both arterial systems
Isolated Retrograde Amnesia
461
provide blood supply to hippocampi and both of them are involved with blood supply to the mesencephalic and pontine areas where reticular nuclei are found. Anterior choroidal artery supplies the hippocampal formation and large portions of the posterior limb of the internal capsule where frontopontine and cortico-reticular fibers are found (Carpenter, 1976). The vertebral basilar system is the source of blood supply for the medial surface of the temporal lobes and to virtually entire pons and mesencephalon including tegmentum (Carpenter, 1976). It is possible that the anterior choroidal and/ or vertebrobasilar insufficiency can lead both to bilateral hippocampal ischemia thus producing a TGA attack, and to some permanent damage to mesencephalic and/ or pontine structures, e.g. infarction thus producing a lesion similar to the one described by Goldberg et al. Given the size of mesencephalic tegmentum, the density of wiring within it, and its being the "bottleneck" for ventrally distributed reticular pathways, it is quite conceivable that a very small lesion in that area can have profound cognitive consequences. The same applies to ventral pontine structures. The tegmental mesencephalic area of hypodensity described by Goldberg et al. was small, such that it could not be revealed by CT scan examinations using 8 mm thickness of cuts; it could be revealed, however, when 5 mm thickness was used. The study by Goldberg et al. was conducted in 1979, three years after Ramon-Campos et al. examined their patient (in 1976). The maximum resolution of CT scanners available in 1976 hardly exceeded 10 mm thickness. It is probable that a CT scan re-examination, using finer resolution which became available with the arrival of recent generations of CT scanners, would shed further light on the mechanisms responsible for memory deficits in the extremely interesting patient described by Roman-Campos et aLit is possible that it would reveal a mesencephalic or (less likely) pontine lesion in the region where it would be likely to destroy reticular nuclei or pathways. Given that the degree of differentiation of reticular projections increases upward along the neural axis and is greater in the mesencephalon than in the pons (Carpenter, 1976) one can expect on a priori grounds that isolated retrograde amnesia would follow mesencephalic tegmental rather than ventral pontine damage. The latter, on the other hand, would be more likely to produce a more generalized deficit involving arousal. Cases of isolated persistent retrograde amnesia are quite rare but not unheard of. It is possible that such cases share not only common cognitive symptomatology but also common neural mechanisms. If this is the case, then a new, distinct neurological and neuropsychological syndrome may
462
Elkhonon Goldberg, James E.O. Hughes, Steven Mattis and Sanford P. Antin
be emerging. The tegmental mesencephalic hypothesis formulated by Goldberg et al, was an attempt to define such mechanisms as a step toward describing this syndrome. Given the rarity of an isolated retrograde amnesia unaccompanied by a comparably severe anterograde amnesia or general arousal deficit, every case is of considerable interest. Further, careful studies of instances of this intriguing condition may contribute in important ways both to theoretical neuroscience and to clinical neurological and neuropsychological taxonomy. ABSTRACT
Two cases of persistent retrograde amnesia are compared. Although etiologies are different (head trauma and transient global amnesia sequelae), it is possible that mechanisms are the same: impairment of selective reticulo-limbic interactions due to brain-stem damage. REFERENCES CARPENTER, M.D. (1976) Human Neuroanatomy, Williams and Wilkins, Baltimore. GOLDBERG, E., ANTIN, S.P., BILDER, R.M., GERSTMAN, L.J. HUGHES, J.E.O., and MATTIS, S. ( 1981) Retrograde amnesia: Possible role of mesencephalic reticular activation in long-term memory, Science, 213, 1392-1394. MOORE, R.Y., and BLOOM, F.E. (1979) Central catecholacemic neuron systems. Anatomy and physiology of the norepinephrine and epinephrine systems, Ann. Rev. Neurosci., 2,
113-168.
ROMAN-CAMPOS, G., POSER, C.M., and WooD, F. (1980) Persistent retrograde memory deficit after transient global amnesia, Cortex, 16, 509-518. SHUTE, D.D.C., and LEWIS, P.R. (1967) The ascending cholinergic reticular system. Neocortical, olfactory and subcortical projections, Brain, 90, 497-520. Elkhonon Goldberg, P.O. Box 88, Department of Psychiatry, Downstate Medical Center of SUNY, 450 Clarkson Avenue, Brooklyn, N.Y. 11203