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The mechanism of transition of interictal spiking foci into ictal seizure discharges Part II: Observations in man
T H E M E C H A N I S M OF T R A N S I T I O N OF I N T E R I C T A L S P I K I N G F O C I I N T O I C T A L SEIZURE DISCHARGES P A R T II: OBSERVATIONS IN M A N t
BRUCEL. RALSTON,M.D. and CHRISTOSA. PAPATHEODOROU,M.D. Department o~ Neurological Surgery, The Mount Sinai Hospital, New York (Received for publication: March 19, 1959)
Previous experimental studies have shown (Ralston 1958) that the transition from interictal spiking into ictal seizure discharge is usually not accomplished by progressive increase of spike frequency to the point of rhythmical discharge, but rather by the interpolation of a new form of electrical activity, the afterdischarge (fig. 1). The afterdischarge is a rapid, rhythmical, low voltage activity that characteristically occurs upon the terminal slow wave of the spike complex. It is, in actuality, an embryo seizure. From it, rather than by fusion of the interictal spike complexes, more extensive seizure activity develops in the great majority of observations made in cats and monkeys, utilizing penicillin as the epileptogenic agent. The recognition of afterdischarge might be a matter of great clinical import, because, unlike the spike itself, which may be projected widely from its origin, the afterdischarge tends to be sharply localized to the epileptic focus itself, or to be projected over only a very limited area. There is considerable difficulty in ascertaining whether homologous activity exists in cases of human convulsive disorder. The low voltage, rapid afterdischarge might not be picked up in scalp EEG recordings or might be obscured by muscle activity. Spontaneous seizures are uncommonly recorded during electrocorticography done for seizure disorder, and even then one is not sure whether the electrodes are on the primary or a projected spike focus. Electrically induced seizures
during craniotomy are not helpful in the solution of this problem, because the morphology of the electrically induced afterdischarge and seizure is quite different from that resulting from a spiking focus. Two questions were raised pursuant to this problem in man. The first, was whether a penicillin-induced focus would behave in the manner typical of the cat and monkey; i.e. pass from spiking to spiking with afterdischarge, and then to more prominent seizure activity. The second, was whether afterdischarge could be observed in a case of epilepsy and whether it could be correlated with clinical evidence of seizure activity.
1. Active Frontal Spiking Focus Induced with Penicillin. No Afterdischarge or Seizure Activity The patient was a 65 year old male with a small (1 cm. diameter) metastatic lesion, primary unknown in the right frontal lobe. Right frontal craniotomy was carried out under nitrous oxide and Pentothal anesthesia. There were no surface abnormalities. Electrodes were placed as indicated in figure 2. Numbers 9, 8, and 7 are located on a Grass depth electrode respectively, at surface, 1 cm. and 2 cm. below the surface. Following preliminary electrocorticography which failed to disclose any epileptiform abnormalities, a cotton pledget, saturated with penicillin (10 e units/cc.) was placed at point P just adjacent to the position of the depth electrode. Within 3 rain. a very active spiking focus was produced which grew in both intensity and sharpness. Although the frequency of occurrence 1 This investigation was supported by a research was as rapid as 3/sec., there was no indication grant from the National Institute of Neurological Diseases and Blindness, of the National Institutes of afterdischarge or of seizure activity during of Health, Public Health Service. the 30 min. period of observation. [ 29~ ]
298
I~RUCE L, RALSTON amt CHRISTOS A. ~'APATHEODOR()U
2. Active Frontal Spiking Focus Induced with Penicillin. Afterdischarge Followed by Focal Seizure The patient was a 56 year old woman who 10 months previously had undergone a complete right temporal lobectomy for glioblastoma multiforme. She had been well for 9 months and had then suffered a return of
. . . . . . . . . . . . . . . . .
ities, ~t pledget of penieilliil-soaked cotton was placed at point P in proximity to electrode 3 h circumscribed spiking focus was established in a few minutes. Within 10 rain. (fig. 3a arrow), a spike complex was observed, followed by a somewhat irregular afterdischarge, and then by another somewhat difo ferent spike complex. This took place at a
-- . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
19-B J
..............................
l .......................
23-x
!
23-~
-]. ............................
!
! ............
-
~:~
i i I
!
2 sec
. . . . . . . . . . . . . . . . ;2c-( . . . . . . . . . . . . . . . . . . . . . "47-'~. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4,-~i
-
i;~
,6-, !
i Fig. 1 Examples of spike and spike-afterdischarge induced by penicillin application in the cat. # 18, 19, 23, 30, 55-tbalamie (VI~, VA, VPL, YL, CM). # 43. 44, 46, 4?-cingulate. Note the variability in appearance of the rhythmical afterdiseharge. Included for comparison of after-discharge with t h a t in man. * Reprinted from 2EI~G Clin. N e u r o p h y s i o L 1958, 10: 217-232.
symptoms. Under nitrous oxide-Pentothal time when spiking was not occurring very anesthesia, the convexity of the entire right rapidly. The configuration of this irregular hemisphere was exposed for the purpose of afterdischarge is somewhat similar to one obcarrying out a hemispherectomy. The elec- served in the cat (fig. 1, 44-B). Following the spikc-afterdischarge, regtrodes were placed as in figure 3. Numbers 3, 2, and 1 were located on a Grass depth elec- ular spike complexes occurred for the next trode respectively, on surface, 1 cm. and 2 minute, although increasing in frequency. The cm. below surface. Following preliminary elec- beginning of the focal seizure is recorded in trocortieography, which showed no abnormal- figure 3b. Here, following the 6th large
EPILEPTIC TRANSITIONAL MECHANISMS IN MAN spike complex, a 7th follows immediately, showing irregular rhythmical waves on the slow component. The 8th and 9th large spike complexes show activity very similar to that observed in the afterdischarge, and following the 9th, there is rapid rhythmical activity
299
afterdischarge and much of the rapid seizure activity is not. In another case, an active spiking focus was produced in the occipital pole. This progressed to afterdischarge but no further during the 30 min. period of observation. In an-
I.J.
CV )-4
t SEC
Fig. 2 Active frontal spiking focus induced by penicillin placed in proximity to electrode 9. No evidence of afterdischarge or seizure formation. For details, see text. which continues, interspersed with large spike complexes. With the onset of this rhythmical activity there is a brief decrease in the frequency of occurrence of the large spike complexes. Although the spiking is transmitted to the depth electrode 1 cm. deep to the focus, the
other instance, a frontal focus was established and activated with Metrazol. A seizure developed, characterized by the development of rapid rhythmical activity between the large spike complexes but not clearly related to the terminal slow wave. In all of the observations on penicillin-
BRUCE L. ~ A L S T O N a~(:l CHRISTOS A. PAPATIIEODOROU
300
induced loci in the human, the loci can be followed only for a relatively short period of time, as compared to hours or days in the experimental animal.
seizures at age 10 years. There was a constant aura of epigastrie sensation, frequently painful, radiating upwards to the head. Following this she wonhl lose consciousness, her fac~:,
t
It 1-2
2-3
"
II~,
,,'k,
k,">j
I!!
Fig. 3 Active frontal spiking focus induced by penicillin placed in proximity to electrode 3. Spiking with afterdischarge leading to focal seizure. For details, see text.
3. Spontaneous Spike-Afterdischarge in a would become red and then she would smack Case of Temporal Lobe Epilepsy. Correla- her lips, chew or rub her genitalia. These tion of Afterdischarge with Onset of Aura attacks had increased in frequency despite The patient was a 44 year old housewife who at the age of 6 months had a generalized seizure associated with high fever. She had no further episodes until the onset of habitual
adequate medication. The patient also had outbreaks of violent temper and claimed that she had extra-sensory perception. Neurological examination was negative. E E G disclosed
EPILEPTIC TRANSITIONAL MECHANISMS IN MAN paroxysmal bursts of 2 c/sec., 50 ~V. activity in the right temporal leads. Metrazol activation resulted in an attack characterized by automatism without aphasia, and preceded by spiking in the right temporal region. Exposure of the right temporal and inferior fronto-parietal region was carried out
301
even more strongly obtained from a depth electrode placed 3 cm. in depth, located 3 cm. back from the temporal tip, presumably in the peri-insular gray or amygdala region.
|
|
C
1-2
r
~
2-$
3-4
4-5
"$ENSAT]ON IN MY STOMAGH"
4-5
7-8 s-
8-9
:Fig. 4
a - polar spiking in a case of temporal lobe epilepsy. b - - o n s e t of spike-afterdischarge coincident with onset of epigastric sensation.
under local anesthesia, without preliminary medication. The postcentral gyrus was identified by threshold stimulation. The epigastric aura could be elicited by electrical stimulation from the first temporal convolution just anterior and posterior to the point of intersection of the central with the Sylvian fissures. It was
9-10
J2Sl
IIC¥
Fig. 5 a, b, c -- examples of spontaneous spike after-discharge occurring coincident with aura. For details, see text. Prior to stimulation, electrocorticography was carried out. There was no spiking activity above the fissure of Sylvius, except for minor projections. Active spiking was obtain-
BRUCE 1,. RALSTON and CHRISTOS A. PAPATHEODOROU
302
ed from the temporal tip at the level of the 2nd and 3rd temporal convolutions (fig. 4a), with slight pickup more posteriorly. At this time the patient did not have any aura. Several minutes later (figure 4b), she complained of her usual epigastric aura. The first spike complex at electrodes 1 and 6 in this illustration has grown in size and is multiphasic but
45
"FIGHTING OFF AN
gradually decreasing in number. This type of afterdischarge is similar to one induced in the cat with penicillin (fig. 1, 43-B). Although the spike is picked up, attenuated, at electrode 2, 2 cm. further posteriorly, there is no transmission of the afterdischarge. Figure 5 (A, B, C) shows placement above and below the fissure of Sylvius. There are
ATTACK"
69
910
.~,~
,%:.
.,
::-\
Fig. 6
Recording made during intense rising epigastric aura. Tracing characterized by recurrent spike-afterdischarge and sharp spikes, mostly restricted to temporal pole (electrode arrangements the same as in figure 4). For details, see text. with no definite afterdiseharge on the slow component. However, the second spike complex shows a well-defined rapid (50/sec.) low voltage afterdischarge. The relation~ship of the afterdischarge to the terminal slow wave is particularly well seen in the third complex, which is followed by a burst of rapid spikes,
large spike complexes with afterdischargc in the anterior temporal region with slight transmission posteriorly and above the fissure of the spike but not the afterdiseharge. As in the previous figure, the spike-afterdischarge is usually followed by additional spikes. In figure 6, the electrodes are arranged
EPILEPTIC TRANSITIONAL MECHANISMS IN MAN
303
as in figure 4. At this time, the epigastrie sensation was very strong and the patient thought that she would lose consciousness. The record is characterized by continuous spike-afterdischarge, mingled with sharp spikes, at the temporal tip. Although the spike complexes are almost of the same intensity at electrodes 1 and 6, and they are separated by only 3 cm., there is more afterdischarge at electrode 1. Following studies, an anterior and middle temporal lobectomy was carried out. Postexcisional tracings showed no spiking from the cortex, insula, or cut surface of the hippocampus. The patient has had no seizures or epigastric aura since surgery.
queney of this occurrence is not yet known. We have not as yet seen a seizure develop simply through an increase in frequency of interictal spike complexes until they are organized into runs of rhythmical activity. The same mechanism of spike-afterdischarge has been found to be operative in a case of temporal lobe epilepsy, where its appearance could be correlated with the onset of the epigastric aura. The detection of spike-afterdischarge should prove to be a means of differentiating the primary spiking focus from a transmitted spike at surgery, both in the resting record and during activation.
DISCUSSION
CONCLUSIONS
It was concluded in a previous study (Ralston 1958), that the phenomenon of spike-afterdiseharge is not a species peculiarity, being obtained with equal facility in the cat and monkey. It is not the property of any single epileptogenie agent, having been recorded with several substances other than penicillin (Chang 1953; Chusid et al. 1953; Hanbery and Ajmone-Marsan 1954). It was also felt that it had a probable counterpart in human epilepsy. Very little is known of the results of application of epileptogenie drugs to the human cortex. Walker (1945) has reported spike discharges following the application of penicillin but there is no description of the transitional mechanism under discussion. With regards to this mechanism of seizure formation in patients with epilepsy, even less is known. A few possible examples of spike-afterdischarge have been culled from the literature (Ralston 1958). The infrequency of occurrence of seizures during electrocorticography for convulsive disorder and the uncertainty of identifying a primary from a projected spike, all contribute to the difficulty. Our experience with the effects of penicillin placed on human cortex, prior to its surgical removal, has shown that spike-afterdischarge may be easily elicited, and may progress to a fully developed seizure. The fre-
1. Application of penicillin to the human cortex has resulted in spike-afterdiseharge, progressing to seizure activity, similar to that observed previously in the cat and the monkey. 2. Spike-afterdiseharge has also been observed in a case of temporal lobe epilepsy and correlated with the onset of aura. R~SUM~ 1. L'applieation de la p~nieilline au cortex humain a donn~ lieu ~ une apr~s-d~eharge en pointe, ~voluant ~ l'activit6 comitiale, sereblable ~ celle observ~e au pr6alable chez le chat et chez le singe. 2. L'apr~s-d~eharge a ~galement ~t~ observ~e chez un eas d'~pilepsie du lobe temporal, e t a ~t~ mise en correlation avec le d~but de l'aura. ZUSAMMENFASSUNG 1. Die Applikation yon Penizillin auf die menschliehe Gehirnrinde erzeugte eine Spitzen-Nachentladung, welche zur AnfaUs-Aktivit~it fortschritt, in ~ihnlicher Weise wie das friiher bei der Katze und beim Affen beobachtet wurde. 2. Die Spitzen-Naehentladung wurde ebenfalls in einem Fall yon Sehl~fenlappenepilepsie beobaehtet und stand mit dem Anfang der Aura in Beziehung.
304
BRUCE L. RALSTON and CHRISTOS A. PAPATHEODOI~OU REFERENCES
(;HANG, H. Similarity in action between curare and strychnine on cortical neurons. J. NeurophysioL, 1953, I 6 : 221-233. CHUSID, J . G., KOPELOFF, L. ~¢~. and KOPELOFF, •. Experimental epilepsy in the monkey following multiple intracerebral injections of alumina cream. BuZl. N.Y. Acad., 1 9 ~ , 39: 898-904. HAI~BERY, J. W. and AJ~ONE-I~CIKRSA~, C. Intrathecal injection and cortical application of chloramphenicol - - an experimental study with a review of
the local action of antibiotics on the central nervous system. J. ,Veuropath. exp. Neurol., 1954, 13: 297-317. RALSTON, B. L. The mechanism of transition of interictal spiking foci into ictal seizure discharges. JgEG Clin. Neurophysiol., 1958, 1 0 : 2 1 7 232. WALKER, A. E., JOHNSOI~, •. C. and KOLLR0S, J. J. Penicillin convulsions. The convulsive effects of penicillin applied to the cortex of monkey and man. Surg. Gynec. Obst., 1945, 8l: 692-701.
Reference: RALS~'ON, B. L. and FAPATHEODOEOU, C . A . The mechanism of transition of intorictat spiking foci into ictal selzure discharges. P a r t I I : Observations in man. E E G C~in. Neurophysiol., 1980, I~: 297-304.
BRUCEL. RALSTON,M.D. and CHRISTOSA. PAPATHEODOROU,M.D. Department o~ Neurological Surgery, The Mount Sinai Hospital, New York (Received for publication: March 19, 1959)
Previous experimental studies have shown (Ralston 1958) that the transition from interictal spiking into ictal seizure discharge is usually not accomplished by progressive increase of spike frequency to the point of rhythmical discharge, but rather by the interpolation of a new form of electrical activity, the afterdischarge (fig. 1). The afterdischarge is a rapid, rhythmical, low voltage activity that characteristically occurs upon the terminal slow wave of the spike complex. It is, in actuality, an embryo seizure. From it, rather than by fusion of the interictal spike complexes, more extensive seizure activity develops in the great majority of observations made in cats and monkeys, utilizing penicillin as the epileptogenic agent. The recognition of afterdischarge might be a matter of great clinical import, because, unlike the spike itself, which may be projected widely from its origin, the afterdischarge tends to be sharply localized to the epileptic focus itself, or to be projected over only a very limited area. There is considerable difficulty in ascertaining whether homologous activity exists in cases of human convulsive disorder. The low voltage, rapid afterdischarge might not be picked up in scalp EEG recordings or might be obscured by muscle activity. Spontaneous seizures are uncommonly recorded during electrocorticography done for seizure disorder, and even then one is not sure whether the electrodes are on the primary or a projected spike focus. Electrically induced seizures
during craniotomy are not helpful in the solution of this problem, because the morphology of the electrically induced afterdischarge and seizure is quite different from that resulting from a spiking focus. Two questions were raised pursuant to this problem in man. The first, was whether a penicillin-induced focus would behave in the manner typical of the cat and monkey; i.e. pass from spiking to spiking with afterdischarge, and then to more prominent seizure activity. The second, was whether afterdischarge could be observed in a case of epilepsy and whether it could be correlated with clinical evidence of seizure activity.
1. Active Frontal Spiking Focus Induced with Penicillin. No Afterdischarge or Seizure Activity The patient was a 65 year old male with a small (1 cm. diameter) metastatic lesion, primary unknown in the right frontal lobe. Right frontal craniotomy was carried out under nitrous oxide and Pentothal anesthesia. There were no surface abnormalities. Electrodes were placed as indicated in figure 2. Numbers 9, 8, and 7 are located on a Grass depth electrode respectively, at surface, 1 cm. and 2 cm. below the surface. Following preliminary electrocorticography which failed to disclose any epileptiform abnormalities, a cotton pledget, saturated with penicillin (10 e units/cc.) was placed at point P just adjacent to the position of the depth electrode. Within 3 rain. a very active spiking focus was produced which grew in both intensity and sharpness. Although the frequency of occurrence 1 This investigation was supported by a research was as rapid as 3/sec., there was no indication grant from the National Institute of Neurological Diseases and Blindness, of the National Institutes of afterdischarge or of seizure activity during of Health, Public Health Service. the 30 min. period of observation. [ 29~ ]
298
I~RUCE L, RALSTON amt CHRISTOS A. ~'APATHEODOR()U
2. Active Frontal Spiking Focus Induced with Penicillin. Afterdischarge Followed by Focal Seizure The patient was a 56 year old woman who 10 months previously had undergone a complete right temporal lobectomy for glioblastoma multiforme. She had been well for 9 months and had then suffered a return of
. . . . . . . . . . . . . . . . .
ities, ~t pledget of penieilliil-soaked cotton was placed at point P in proximity to electrode 3 h circumscribed spiking focus was established in a few minutes. Within 10 rain. (fig. 3a arrow), a spike complex was observed, followed by a somewhat irregular afterdischarge, and then by another somewhat difo ferent spike complex. This took place at a
-- . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
19-B J
..............................
l .......................
23-x
!
23-~
-]. ............................
!
! ............
-
~:~
i i I
!
2 sec
. . . . . . . . . . . . . . . . ;2c-( . . . . . . . . . . . . . . . . . . . . . "47-'~. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4,-~i
-
i;~
,6-, !
i Fig. 1 Examples of spike and spike-afterdischarge induced by penicillin application in the cat. # 18, 19, 23, 30, 55-tbalamie (VI~, VA, VPL, YL, CM). # 43. 44, 46, 4?-cingulate. Note the variability in appearance of the rhythmical afterdiseharge. Included for comparison of after-discharge with t h a t in man. * Reprinted from 2EI~G Clin. N e u r o p h y s i o L 1958, 10: 217-232.
symptoms. Under nitrous oxide-Pentothal time when spiking was not occurring very anesthesia, the convexity of the entire right rapidly. The configuration of this irregular hemisphere was exposed for the purpose of afterdischarge is somewhat similar to one obcarrying out a hemispherectomy. The elec- served in the cat (fig. 1, 44-B). Following the spikc-afterdischarge, regtrodes were placed as in figure 3. Numbers 3, 2, and 1 were located on a Grass depth elec- ular spike complexes occurred for the next trode respectively, on surface, 1 cm. and 2 minute, although increasing in frequency. The cm. below surface. Following preliminary elec- beginning of the focal seizure is recorded in trocortieography, which showed no abnormal- figure 3b. Here, following the 6th large
EPILEPTIC TRANSITIONAL MECHANISMS IN MAN spike complex, a 7th follows immediately, showing irregular rhythmical waves on the slow component. The 8th and 9th large spike complexes show activity very similar to that observed in the afterdischarge, and following the 9th, there is rapid rhythmical activity
299
afterdischarge and much of the rapid seizure activity is not. In another case, an active spiking focus was produced in the occipital pole. This progressed to afterdischarge but no further during the 30 min. period of observation. In an-
I.J.
CV )-4
t SEC
Fig. 2 Active frontal spiking focus induced by penicillin placed in proximity to electrode 9. No evidence of afterdischarge or seizure formation. For details, see text. which continues, interspersed with large spike complexes. With the onset of this rhythmical activity there is a brief decrease in the frequency of occurrence of the large spike complexes. Although the spiking is transmitted to the depth electrode 1 cm. deep to the focus, the
other instance, a frontal focus was established and activated with Metrazol. A seizure developed, characterized by the development of rapid rhythmical activity between the large spike complexes but not clearly related to the terminal slow wave. In all of the observations on penicillin-
BRUCE L. ~ A L S T O N a~(:l CHRISTOS A. PAPATIIEODOROU
300
induced loci in the human, the loci can be followed only for a relatively short period of time, as compared to hours or days in the experimental animal.
seizures at age 10 years. There was a constant aura of epigastrie sensation, frequently painful, radiating upwards to the head. Following this she wonhl lose consciousness, her fac~:,
t
It 1-2
2-3
"
II~,
,,'k,
k,">j
I!!
Fig. 3 Active frontal spiking focus induced by penicillin placed in proximity to electrode 3. Spiking with afterdischarge leading to focal seizure. For details, see text.
3. Spontaneous Spike-Afterdischarge in a would become red and then she would smack Case of Temporal Lobe Epilepsy. Correla- her lips, chew or rub her genitalia. These tion of Afterdischarge with Onset of Aura attacks had increased in frequency despite The patient was a 44 year old housewife who at the age of 6 months had a generalized seizure associated with high fever. She had no further episodes until the onset of habitual
adequate medication. The patient also had outbreaks of violent temper and claimed that she had extra-sensory perception. Neurological examination was negative. E E G disclosed
EPILEPTIC TRANSITIONAL MECHANISMS IN MAN paroxysmal bursts of 2 c/sec., 50 ~V. activity in the right temporal leads. Metrazol activation resulted in an attack characterized by automatism without aphasia, and preceded by spiking in the right temporal region. Exposure of the right temporal and inferior fronto-parietal region was carried out
301
even more strongly obtained from a depth electrode placed 3 cm. in depth, located 3 cm. back from the temporal tip, presumably in the peri-insular gray or amygdala region.
|
|
C
1-2
r
~
2-$
3-4
4-5
"$ENSAT]ON IN MY STOMAGH"
4-5
7-8 s-
8-9
:Fig. 4
a - polar spiking in a case of temporal lobe epilepsy. b - - o n s e t of spike-afterdischarge coincident with onset of epigastric sensation.
under local anesthesia, without preliminary medication. The postcentral gyrus was identified by threshold stimulation. The epigastric aura could be elicited by electrical stimulation from the first temporal convolution just anterior and posterior to the point of intersection of the central with the Sylvian fissures. It was
9-10
J2Sl
IIC¥
Fig. 5 a, b, c -- examples of spontaneous spike after-discharge occurring coincident with aura. For details, see text. Prior to stimulation, electrocorticography was carried out. There was no spiking activity above the fissure of Sylvius, except for minor projections. Active spiking was obtain-
BRUCE 1,. RALSTON and CHRISTOS A. PAPATHEODOROU
302
ed from the temporal tip at the level of the 2nd and 3rd temporal convolutions (fig. 4a), with slight pickup more posteriorly. At this time the patient did not have any aura. Several minutes later (figure 4b), she complained of her usual epigastric aura. The first spike complex at electrodes 1 and 6 in this illustration has grown in size and is multiphasic but
45
"FIGHTING OFF AN
gradually decreasing in number. This type of afterdischarge is similar to one induced in the cat with penicillin (fig. 1, 43-B). Although the spike is picked up, attenuated, at electrode 2, 2 cm. further posteriorly, there is no transmission of the afterdischarge. Figure 5 (A, B, C) shows placement above and below the fissure of Sylvius. There are
ATTACK"
69
910
.~,~
,%:.
.,
::-\
Fig. 6
Recording made during intense rising epigastric aura. Tracing characterized by recurrent spike-afterdischarge and sharp spikes, mostly restricted to temporal pole (electrode arrangements the same as in figure 4). For details, see text. with no definite afterdiseharge on the slow component. However, the second spike complex shows a well-defined rapid (50/sec.) low voltage afterdischarge. The relation~ship of the afterdischarge to the terminal slow wave is particularly well seen in the third complex, which is followed by a burst of rapid spikes,
large spike complexes with afterdischargc in the anterior temporal region with slight transmission posteriorly and above the fissure of the spike but not the afterdiseharge. As in the previous figure, the spike-afterdischarge is usually followed by additional spikes. In figure 6, the electrodes are arranged
EPILEPTIC TRANSITIONAL MECHANISMS IN MAN
303
as in figure 4. At this time, the epigastrie sensation was very strong and the patient thought that she would lose consciousness. The record is characterized by continuous spike-afterdischarge, mingled with sharp spikes, at the temporal tip. Although the spike complexes are almost of the same intensity at electrodes 1 and 6, and they are separated by only 3 cm., there is more afterdischarge at electrode 1. Following studies, an anterior and middle temporal lobectomy was carried out. Postexcisional tracings showed no spiking from the cortex, insula, or cut surface of the hippocampus. The patient has had no seizures or epigastric aura since surgery.
queney of this occurrence is not yet known. We have not as yet seen a seizure develop simply through an increase in frequency of interictal spike complexes until they are organized into runs of rhythmical activity. The same mechanism of spike-afterdischarge has been found to be operative in a case of temporal lobe epilepsy, where its appearance could be correlated with the onset of the epigastric aura. The detection of spike-afterdischarge should prove to be a means of differentiating the primary spiking focus from a transmitted spike at surgery, both in the resting record and during activation.
DISCUSSION
CONCLUSIONS
It was concluded in a previous study (Ralston 1958), that the phenomenon of spike-afterdiseharge is not a species peculiarity, being obtained with equal facility in the cat and monkey. It is not the property of any single epileptogenie agent, having been recorded with several substances other than penicillin (Chang 1953; Chusid et al. 1953; Hanbery and Ajmone-Marsan 1954). It was also felt that it had a probable counterpart in human epilepsy. Very little is known of the results of application of epileptogenie drugs to the human cortex. Walker (1945) has reported spike discharges following the application of penicillin but there is no description of the transitional mechanism under discussion. With regards to this mechanism of seizure formation in patients with epilepsy, even less is known. A few possible examples of spike-afterdischarge have been culled from the literature (Ralston 1958). The infrequency of occurrence of seizures during electrocorticography for convulsive disorder and the uncertainty of identifying a primary from a projected spike, all contribute to the difficulty. Our experience with the effects of penicillin placed on human cortex, prior to its surgical removal, has shown that spike-afterdischarge may be easily elicited, and may progress to a fully developed seizure. The fre-
1. Application of penicillin to the human cortex has resulted in spike-afterdiseharge, progressing to seizure activity, similar to that observed previously in the cat and the monkey. 2. Spike-afterdiseharge has also been observed in a case of temporal lobe epilepsy and correlated with the onset of aura. R~SUM~ 1. L'applieation de la p~nieilline au cortex humain a donn~ lieu ~ une apr~s-d~eharge en pointe, ~voluant ~ l'activit6 comitiale, sereblable ~ celle observ~e au pr6alable chez le chat et chez le singe. 2. L'apr~s-d~eharge a ~galement ~t~ observ~e chez un eas d'~pilepsie du lobe temporal, e t a ~t~ mise en correlation avec le d~but de l'aura. ZUSAMMENFASSUNG 1. Die Applikation yon Penizillin auf die menschliehe Gehirnrinde erzeugte eine Spitzen-Nachentladung, welche zur AnfaUs-Aktivit~it fortschritt, in ~ihnlicher Weise wie das friiher bei der Katze und beim Affen beobachtet wurde. 2. Die Spitzen-Naehentladung wurde ebenfalls in einem Fall yon Sehl~fenlappenepilepsie beobaehtet und stand mit dem Anfang der Aura in Beziehung.
304
BRUCE L. RALSTON and CHRISTOS A. PAPATHEODOI~OU REFERENCES
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