Electroencephalography and Clinical Neurophysiology, 1979, 46: 7P--14P
7P
© Elsevier/North-Holland Scientific Publishers, Ltd. Society proceedings EASTERN ASSOCIATION OF ELECTROENCEPHALOGRAPHERS WITH THE AMERICAN EPILEPSY SOCIETY)
(JOINT MEETING
New York City, November 29--30, 1977
Secretary-Treasurer: Dr. G. ERBA Department of Neurology, Seizure Unit, Children's Hospital Medical Center, 300 Longwood Avenue, Boston, Mass. 02115 (U.S.A.) 1. Clinical significance of the epileptogenic properties of psychotropic d r u g s . - T.M. Itil and C. Soldatos (New York, N.Y.) Neuroleptics generally increase spikes, sharp waves and paroxysmal groups in the EEG. Potently sedative neuroleptics induce epileptic activity and clinical convulsions more frequently than less sedative but extrapyramidally more effective neuroleptics. Antidepressants in higher doses may increase epileptic activity only in epileptic patients. Lithium alone has definite epileptogenic properties. Anxiolytics have antiepileptic effects, although some epileptic effects have been rarely reported. Other psychotropic drugs (reserpine, hallucinogenics, etc.) also were found epileptogenic by some authors. Epileptogenic effects depend on the convulsive properties of the drug, its dosage and the predisposition of the subject. For example, phenothiazines with aliphatic chains are more epileptogenic, whereas piperazine phenothiazines elicit minimal convulsive activity. Even less epileptogenic drugs, however, may induce epileptic activity in higher doses or with sudden changes in the dosage. The subject's convulsive threshold is most important. Individual predisposition, especially in patients with organic brain syndrome and epileptics, must be carefully considered before starting medication using EEG, medical history and neurological examination. However, psychotropic drugs in proper dosage and combined with antiepileptic medication are not contraindicated in carefully selected psychotic patients with seizures. Systematic EEG monitoring is helpful. Epileptogenic drug effects are practically negligible for subjects without low convulsive thresholds.
2. The EEG in a New York City municipal chronic disease h o s p i t a l . - - R . S . April (Roosevelt Island, N.Y.) The purpose of this report is to analyze statistically the EEGs recorded at Bird S. Coler Hospital,
an active 1246 bed municipal hospital for chronic diseases. The results of 740 consecutive EEGs during the years 1975 and 1976 will be presented with the patients' clinical diagnoses, anatomical confirmations, age and sex. Our EEG laboratory serves a unique population, the majority of whom come from ethnic and racial minorities, are at the poverty level, and suffer from chronic vascular, traumatic, degenerative, and genetic neurologic diseases. EEGs in this setting will be compared to those in published surveys from general hospitals. The differences will be described and illustrated in order to demonstrate the application and usefulness of EEG in our unique clinical population.
3. A piezoelectrical hypothesis for the origin of the alpha rhythm. -- R. Cohn (Washington, D.C. ) In an earlier study of the parametric nature of the concatenated EEG it was suggested that the alpha rhythm might be a direct result of the intermittent pressure of the blood mass on the cortical nervous net. The experimental design to develop this idea was to effect the cessation of all the blood to the brain. Initially this was attempted by unilateral vagus nerve stimulation; this method was not effective. Consequently, decapitation was employed. The electrical effect of decapitation of the gerbil forms the basis of this report. During the initial first 1/2 sec after the operation there was a remarkably decreased EEG output; this was succeeded for the next 1.5 sec by high voltage slow waves. For the next 10 sec there was a rapidly progressive decrease to zero of the electric activity. The initial 1/2 sec response was considered to be the direct effect of the cessation of intermittent pressure. The subsequent electrical activities were believed to be the result of irritative and other random agonal potential variations. The observed phenomena, although obviously not conclusive, do point to a possible piezoelectrical origin of the concatenated alpha rhythm.
8P 4. A predictor o f spike-wave bursts in petit mal EEG. - - A . Siegel, A.F. Mirsky and C.L. Grady (Boston, Mass. ) We previously r e p o r t e d a signal in pre-ictal EEG of approaching spike-wave bursts, highly successful in one patient. Pursuing this work, we have tested it on another patient, whose inter-ictal EEG is m u c h less normal. Inter-ictal fluctuations made the signals m u c h m o r e erratic in this case. It thus became necessary to test for this patient the basic hypothesis o f the existence of a feature in pre-burst EEG significantly correlated with the occurrence of bursts. We averaged spectra f r o m r a n d o m l y selected epochs of pre-bursts. T w o tendencies were observed: a decrease in energy at higher frequencies (above 10 Hz), and a more than compensating increase at lower frequencies. The quantity, energy increase at lower frequencies minus energy decrease at higher frequencies, was used as a statistic in the Wilcoxon rank-sum test; pre-burst samples outranked the others, with P < 0.0002. The procedure used was data-independent t h r o u g h o u t . It should be a straightforward m a t t e r to synthesize a pre-burst signal f r o m the above statistic, roughly as successful as that found with the first patient. The present m e t h o d is m u c h more readily adaptable to individual variations in inter-ictal EEG.
5. Periodic discharge of unusually slow character in neonatal status epilepticus caused by necrotizing encephalitis (herpes s i m p l e x ) . - F. Fineyre (Paris, France and Baltimore, Md.) An eleven-day-old n e w b o r n acutely developed the clinical s y m p t o m a t o l o g y of a CNS infection. Convulsions associated with h y p e r t h e r m i a started 3 days later. Initial EEG examinations showed no abnormalities. On the 16th day o f life, a status epilepticus with irregular and chiefly clonic convulsions materialized involving the right limbs to a greater degree. The infant was placed under massive dosages of anticonvulsants. At this stage, the EEG was severely abnormal with a periodic discharge consistently localized over the right temporal region. In the inter-ictal state, the discharge occurred at intervals of 2--4 sec, mostly against a featureless background. At the start of each seizure, ictal activity originated f r o m the right central area with repetitive spikes (about 1/sec). The slow periodic discharge over right t e m p o r a l area o f t e n persisted during the attacks. In the following, the discharge became bitemporal. Without p r o f o u n d coma, the EEG gradually flattened and the infanf died one m o n t h later. A u t o p s y c o n f i r m e d the clinical diagnosis o f herpes
SOCIETY PROCEEDINGS simplex encephalitis; there was marked necrosis in b o t h temporal lobes. This type of very slowly repetitive discharge is probably analogous to the periodic discharge of adult life herpes simplex encephalitis and differs f r o m o t h e r periodic patterns.
6. A unique EEG pattern in mucolipidosis. -- D. Bergen (Chicago, Ill.) This reports unique EEG features in a patient with mucolipidosis. A s y n d r o m e combining features of both the sphingolipidoses and the mucopolysaccharidoses has been well d o c u m e n t e d . A 19-year-old man with this disease was retarded and had generalized seizures. His EEG showed e x t r e m e l y sharp, bilateral spikes and polyspikes with striking and unusual characteristics: they usually appeared to be positive at the vertex, with a large field extending anteriorly and posteriorly parasagittally; they were n o t seen, or occurred with m u c h lower amplitude, in the temporal region. Bursts of polyspikes were often followed by slow waves but at o t h e r times occurred on the crest of such waves. These positive spikes were seen with the patient awake and asleep, and were clearly different in form and distribution from '14 and 6 positive spikes'. Spike duration was usually less than 20 msec, and some spikes were so sharp as to appear similar to muscle potentials. This pattern is entirely unlike any described previously in patients with either sphingolipidoses or mucopolysaccharidoses. It is, however, identical to that r e p o r t e d in another patient with mucolipidosis. These very sharp positive spikes may represent a unique EEG pattern which may be diagnostic for this rare disease.
7. F I R D A , periventricular edema and normal pressure hydrocephalus.--W.H. Leschey, Jr., R.C. Briggs and L.R. Altemus (Portland, Maine) A case of a 73-year-old w o m a n with typical clinical and radiological manifestations of normal pressure hydrocephalus (NPH) is presented. Pre-shunting and post-shunting psychometrics, EEGs, isotope cisternograms and CT scans are shown. The preoperative EEG consisted of f r e q u e n t frontal i n t e r m i t t e n t r h y t h m i c delta activity ( F I R D A ) bursts superimposed on a normal background. The postoperative EEG was essentially normal with no F I R D A . Analysis of the cisternographic data suggested transmural ventricular absorption of isotope. The CT scans were interpreted as showing varying degrees of periventricular edema. The reversibility of the F I R D A pattern and of the clinical and radiological signs of NPH suggests a probable significant relationship. The relevant pathophysiology of F I R D A , NPH and periventricular
EASTERN ASSOCIATION OF EEGers edema is discussed. Periventricular edema independent of pressure and ventricular size is postulated as the major factor in the production of F I R D A in obstructive hydrocephalus. Further study of F I R D A as a physiological prognosticator in NPH and clarification of the relationship with periventricular edema are needed.
8. EEG studies in hepatic encephalopathy. 'Blind' EEG evaluation. -- T. Riley, F. Fineyre, W.C. Maddrey and E. Niedermeyer (Baltimore, Md.) The treatment of 3 patients (age 32, 47 and 59 years) with advanced cirrhosis of the liver and recurrent episodes of hepatic encephalopathy was monitored by bi-weekly EEG evaluations. A total of 43 records were obtained. All patients were on a protein restricted diet (30 g/day) and were receiving lactulose (90 mg/day) throughout. The study therapies were calcium and arginine salts of ketoanalogues of branched chain amino acids. The electroencephalographers remained without information about the patient's clinical condition and therapy. In addition to visual analysis, power spectra were used occasionally. The degree of slow activity was reflected by graded abnormalities ranging from minimally to very abnormal. All 3 patients responded to the study treatment; decreased lethargy, disappearance of asterixis and improved cortical function testing were observed with treatment. In two patients, improvement and deterioration of the EEG coincided with initiation and discontinuation of treatment but EEG normalization did not materialize. The third patient had normal records between bouts of worsening but the first normalization occurred already in the state of baseline treatment (diet, lactulose). This study provides further evidence for the quick EEG response to changes of the clinical picture of hepatic encephalopathy.
9. 'Ambiguous' REM-NREM in progressive supranuclear palsy treated with L - D O P A . - C. Stafford and L. Green (Philadelphia, Pa.) A single case of progressive supranuclear palsy, treated with L-DOPA showed inter-stage sleep for prolonged periods during an all night sleep study. During these episodes, the EEG showed well formed spindles and vertex activity while striking REM and muscular atony were present. Ambiguous sleep stages have been seen frequently in narcoleptic patients, particularly on amphetamine therapy. Previous studies of sleep parameters in Steel-Richardson syndrome demonstrated suppressed REM and abnormal stage
9P 2 sleep but not ambiguous sleep. Monoamine medication may be involved in the development of prolonged inter-stage sleep.
10. Alcohol, alcoholism (New York, N.Y.)
and
epilepsy. -- R.
Jaffe
The direct relationship of alcohol ingestion to seizure and to epilepsy in general is one of the axioms of epileptology. Critical review of the literature raises serious questions as to the validity of this axiom based on limited early studies reporting high incidence of abnormal EEGs in alcoholics with seizures. Other reports derive from populations not clearly defined either clinically or electroencephalographically. There is recent evidence that 'alcoholic epilepsy' is a condition associated with a normal EEG, and without therapeutic response to phenytoin. This report presents data derived from EEGs of patients admitted for alcoholism and seizures. Out of 75 consecutive admissions in one institution, 52 EEGs were normal and 23 abnormal. Out of 33 admissions in the second institution, 28 EEGs were normal and 5 abnormal. Differences between institutions are attributable to socio-economic factors distinguishing the patient populations. None of the EEG abnormalities was characteristically 'epileptiform'; most were explained on the basis of previous head injuries, CVA, etc. The hypothesis is offered that 'alcoholic epilepsy' is a condition sui generis, and that the presumed relationship of alcohol to the illness defined as 'primary generalized epilepsy', or its manifestations, may be coincidental rather than causal. 11. Stereoelectroencephalographic (SEEG) study of five cases of primary amygdalo-hippocampal epilepsy. -- J.-M. Saint-Hilaire, G. Bouvier, A. Leduc and G. Bouillon (Montreal, Canada) A very precise system has been developed to record clinical epileptic seizures from scalp and depth electrodes, to allow exact anatomical, electrical and clinical correlations (Un. reed. Can., 1976, 105: 1538--1541, and Epilepsia, 1977, 18: 285). We studied 5 cases of primary amygdalo-hippocampal seizures; 3 from the hippocampus and 2 from the amygdala. To differentiate primary involvement of the amygdala from the hippocampus, we have studied various parameters: (1) interictal slow and epileptiform activity recorded from scalp and depth electrodes, (2) ictal activity during numerous spontaneous seizures, (3) results of electrical stimulation, and (4) detailed clinical analysis of spontaneous seizures and of symptoms induced by electrical stimulation.
]0P In primary hippocampal epilepsy, EEG slow activity tends to appear more diffusely over the involved hemisphere and epileptic activity takes a bilaterally synchronous form, p r e d o m i n a t i n g over the involved hemisphere. In primary epilepsy of the amygdala, the epileptic and slow activities are m o r e localized to the corresponding t e m p o r a l lobe. In the depth, hippocampal epilepsy gives rise to ictal activity which spreads more diffusely, particularly to the cingulate and frontal cortex. Clinically, the study of s p o n t a n e o u s seizures and electrical stimulation showed that 'fear' and ' c h e w i n g ' probably originate in the amygdala while 'nausea' comes from the hippocampus.
12. A m i n o acid levels in 3/see spike-wave epilepsy. -N. Aslam, J.D. Metrackos, K. Metrackos and N.J. Van Gelder (Montreal, Canada) The mean serum levels o f 14 free amino acids from 14 patients with 3/sec spike-wave epilepsy were compared with 22 controls. The m e a n values for certain simple and c o m p o u n d ratios of these acids were also compared. Statistically significant differences, some at the 0.001% levels, were o b t a i n e d f r o m 4 o f the 3 amino acids tested and for 4 of the ratios. On the basis of the amino acid levels alone and e m p l o y i n g a m o d i f i c a t i o n of the Walker index for multivariant analysis, it has been possible to separate the epileptics f r o m the controls with a very high degree of reliability. The possible neurobiochemical significance o f these findings, particularly in reference to aspartic acid, glutamic acid and taurine will be discussed.
13. A microprocessor device for data acquisition and averaging of brain stem auditory r e s p o n s e s . R.G. Bickford, D.A. Brittain, K.R. Hanson and D.S. Karnaze (La Jolla, Calif.) Brain stem evoked response techniques (far-field) have rapidly established their clinical value in the diagnosis o f neuronal m a t u r a t i o n in the newborn and a variety of a u d i t o r y and brain stem lesions in older patients. Since this technique is frequently used in the nursery and the ICU with ill or c o m a t o s e patients, there is need for specially designed, c o m p a c t equipm e n t for easy use under these difficult environmental circumstances. The ' E R A ' (evoked response averager) system has been designed specifically for o p e r a t i o n under these conditions. It consists of the following modules contained in a single carrying case weighing 34 lb (15.5 kg): (a) click generator with stepwise dB intensity adjustment; (b) stimulus c o u n t e r ; (c) elect r o d e impedance tester; (d) bioamplifiers of a p p r o -
SOCIETY PROCEEDINGS priate band pass ( 1 0 0 - - 3 0 0 0 Hz); (e) amplitude editor (manual or a u t o m a t i c ) for suppression of 'overload artifact'; (f) microprocessor (Intel 8080) unit for response averaging; (g) oscilloscope for display of EEG or accumulating average during the e x p e r i m e n t ; (h) manually movable cursor for amplitude and latency measures. The system works with a small separate m i n i p l o t t e r (Simpson) w h e n a hard copy or superimposed traces are required. Testing in normal subjects and patients has shown excellent utility of the system under trying conditions of the emergency r o o m , ICU, and nursery. Examples of its clinical application will be shown.
14. Automatic high speed detection of human sleep variables using a hardware pre-processor.- R. Broughton, D. Green, O. Sherif, J. Mary and B. da Costa (Ottawa, Canada) A hybrid approach has been chosen to perform high speed, automatic, inexpensive analysis of h u m a n sleep. It combines a hardware pre-processor to detect E E G polygraphic events with subsequent staging by a microprocessor. Recordings c o m e f r o m a m b u l a n t subjects using portable 4-channel recorders permitting acquisition of 24 h of data on one cassette. Playback and detection is at 20x recording speed. Only those variables essential for h u m a n sleep staging are detected. Their accuracy is c o m p a r e d to multiple (3) blind h u m a n scoring. Alpha r h y t h m is detected by a circuit using a phase-locked loop (PLL) which gives an analogue pulse for presence or absence of a 8--12.5 c/sec, over 20 pV, more or less sinusoidal, activity from a referential occipital-ear derivation. Concordance with consensus h u m a n scoring to these criteria was 92%. Spindles are detected by a similar PLL circuit for 11.5--15 c/sec, over 25 pV, sinusoidal bursts, lasting 0.5 sec or more, in a central-ear derivation: concordance was 85%. K c o m p l e x e s are detected with 91% c o n c o r d a n c e by a m a t c h e d filter approach, based on a charge-coupled device. Delta activity is detected by baseline crossing and period analysis, s u p p l e m e n t e d by an amplitude criterion, for 0.3--2.5 c/sec, over 75/2V activity and c o n c o r d e d 92%. REMs and muscle t o n e are also detected.
15. Brain stem auditory evoked responses: normal variations in humans and utility of monaural stimulation in clinical neurology. --K.H. Chiappa and K.S. Gladstone (Boston, Mass.) In brain stem auditory evoked responses (BAER), the I, III and IV--V waves are the ones m o s t comm o n l y used for evaluation of possible abnormalities
EASTERN ASSOCIATION OF EEGers in patiens. BAERs were recorded from 50 normal subjects. Six different patterns of the wave IV--V complex and 2 forms of wave III were recognized. About half the subjects had similar wave forms in both ears; the other half had dissimilar wave forms, although the degree of dissimilarity was usually less than that seen between different subjects. Repeat recordings, in some subjects over up to 1 year, showed these patterns to remain essentially unchanged. Masking white noise in the unstimulated ear changed the shape of the IV--V complex. Monaural stimulation is also often useful in clinical neurological cases (examples of this will be shown).
16. Somatosensory evoked far-field potentials in patients with multiple sclerosis.- B.J. Anziska, R.Q. Cracco, A.W. Cook and E. Feld (Brooklyn, N.Y.) Somatosensory evoked far-field potentials to separate stimulation of the left and right median nerves were recorded from the scalp of 15 normal subjects and 26 patients with definite multiple sclerosis (McAlpine's criteria). In normal subjects these farfield potentials consist of 3 positive potentials thought to arise in subcortical regions including the brain stem and diencephalon, followed by a negative potential which is thought to reflect the arrival of the afferent volley in cerebral cortical elements. The criteria for abnormality in the patient group were (a) absence of components consistently recorded in normal subjects, and (b) statistically significant component peak latency differences in patients compared to controls. Over 80% of the patients were judged to be abnormal based on these criteria. Most of the patients had absence of some component(s) consistently recorded in normal subjects. Sequential recordings obtained in 4 patients revealed loss or appearance of components or latency changes. Significant alterations in the evoked potentials were observed in some of these patients in the absence of apparent clinical change. It seems that this method will prove useful in the evaluation of some patients with brain stem and diencephalic dysfunction.
17.Deviant topography of somatosensory evoked potentials in s c h i z o p h r e n i a . - G. Shagass, R.A. Roemer, J.J. Straumanis and M. Amadeo (Philadelphia., Pa. ) In studies aimed at establishing evoked potential (EP) correlates of psychiatric illness, the topographic dimension has hitherto received little attention. We
11P present here results obtained by comparing somatosensory (SEP) topography in schizophrenics, nonpsychotic psychiatric patients, and non-patients matched for age and sex (25 in each group). Patients were free of drugs for a median of 10 days. Right and left median nerves were stimulated with 0.1 msec duration pulses 10 mA above sensory threshold. SEPs were recorded from 14 scalp leads and an EOG lead (linked ear reference). Successive SEP peaks were visually detected with a cursor program in the contralateral post-central leads; their latencies were stored and used to measure amplitudes automatically in all leads at these latencies. Spatial distributions of individual peaks were plotted and amplitude differences between groups were compared by multivariate analysis of variance and profile analysis. The main findings showed significant posterior displacement of P30 and N60 peaks in the schizophrenic patients, compared to non-psychotic patients and controls; topographies were similar in the latter two groups. Deviant SEP topography in chronic schizophrenics appears to parallel the posteriorly displaced regional cerebral blood flow reported in such patients by other investigators.
18. EEG changes with seizures induced by immunologic assault in the rat. - - J . G . Franke, V.A. Lennon, C.S. Selzor and R.G. Bickford (La Jolla, Calif. ) The occurrence of generalized and focal seizures was observed in the course of hyperacute autoimmune allergic encephalomyelitis (HEAE) experiments in the rat (V. Shorn, Neurosci. Abstr., 1976: 19). Additional experiments now define the model. Thirteen Lewis rats were prepared as follows: (a) 5 rats were injected with guinea pig myelin basic protein; (b) 3 rats were adrenalectomized and then treated by passive transfer of 'activated lymphocytes' from HEAE rats; (c) 5 rats were treated as controls for the above procedures. In all animals, EEG was recorded with skull screws and low noise cable before, during, and after procedures with spectral estimates (CSA). (1) The normal rat EEG shows considerable change with behavior, and many sharp transients and 'epileptiform patterns' are observed. (2) Rats developing clinical seizures show significant spectral changes in the pre-seizure period. (3) The animals with clinical seizures show florid focal and generalized patterns including diffuse synchronized spike and wave. (4) Seizure activity occurred in all animals of groups (a) and (b). Now seizures or significant discharges occurred in control animals. This immunologic model of epilepsy in the rat is of current interest in view of reported findings of
12P immunologic abnormalities in patients with constitutional type of epilepsy.
19. Effects o f changes in cortical excitability upon the spike and wave bursts in generalized penicillin epilepsy o f the cat. -- A. Pellegrini and P. Gloor (Montreal, Canada) Previous studies had suggested that the spike and wave bursts of feline generalized epilepsy represent the response of hyperexcitable cortex to thalamocortical volleys normally evoking spindles. If this were the ease, it should be possible to convert spike and wave bursts in generalized penicillin epilepsy into spindles by decreasing the excitability of cortical neurons. Cortical excitability was decreased (a) by hypoxia, (b) by topical application to the cortex of KC1, (c) GABA, or (d) barbiturates. During generalized penicillin epilepsy, KC1 induced spreading depression and hypoxia abolished spike and wave bursts which were replaced by spindles. Topical application of GABA or of barbiturates reduced or inverted the negative spikes of the spike and wave complexes, while augmenting the negative slow waves, or revealing them clearly when they had been poorly developed. This effect is probably due to selective inactivation of the superficial cortical layers. These results are compatible with the hypothesis that spike and wave complexes are induced by corticopetal volleys normally involved in spindle genesis. This is further supported by the fact that if spindles and spike and waves occurring in the same animal are compared, a direct correlation between the frequencies of these two rhythms can be demonstrated.
20. 'Drop epileptic seizures': atonic, tonic, myoclonic components ; clinical and electrophysiological c o r r e l a t e s . - C.T. Lombroso and G. Erba (Boston, Mass.) By utilizing techniques of continuous EEG, video, and at times EMG monitoring, we have analyzed closely a group of epileptic patients in whom 'drop seizures' were common. We observed a spectrum of clinical manifestations ranging from single or repetitive head drops, to whole body akinesia, mixed on some occasions with what appear myoclonic or tonic manifestations. Concomitant EEG discharges varied from bursts of slow waves or spike waves to fast recruiting rhythms or a combination of the three. Fast recruiting discharges very often accompanying major atonic seizures could not be distinguished from those accompanying a tonic seizure. Likewise, spikewave bursts during an atonic head drop did not appear different from those occurring in absences
SOCIETY PROCEEDINGS with or without head bobbing or with tonic upward deviation of the eyes. It appears that opposite peripheral phenomena such as paroxysmal increase or decrease in tonic muscular activity may be accompanied by similar EEG correlates. Thus, EEG discharges alone, although always generalized and synchronous, are in these cases not specific for various ictal phenotypes. A subcortical, possibly brain stem origin, might explain the above variability in EEG and peripheral ictal phenomena implying now excitatory, now inhibitory influences upon spinal m o t o r function.
21. Computed EEG topography (CET) of paroxysmal and background activity in seizure d i s o r d e r s . R.N. Harner and K.A. Ostergren (Philadelphia, Pa.) Computed EEG topography (CET) is a new method that displays individual waves according to their amplitude, duration, and channel of origin, producing a quasi-anatomical 'head'. and stores data for off-line display or computation. The CET retains and quantifies much information that is useful for clinical EEG interpretation ( E l e c t r o e n c e p h . clin. N e u r o p h y s i o l . , 1977, 42: 721). However, the real test of such a method is its applicability to the study of epilepsy. During 8 months, 45 CETs obtained from persons referred for seizures were interpreted independently of the routine EEG or the clinical history. CET findings in 21 cases with underlying gross lesion included focal abnormalities in 17, paroxysmal features in 10 (1 bilateral spike-wave) and focal depression of background activity in 11. In 10 cases with focal seizures and no gross lesion, 9 CETs were focal, 8 paroxysmal (1 bilateral spike-wave) and no instance of focal depression, In 14 non-focal cases, the CET showed focal spikes in 2, bilateral paroxysmal features in 8 (7 spike-wave), and no focal depression. The CET retains significant information concerning the nature and location of EEG disturbances in epilepsy. A combination of visual display and quantitative output effectively summarizes that information for clinical use.
22. Cycloheximide suppression of kindling is not an anticonvulsant effect. -- E. Kessler, E. Moneta and F. Morrell (Chicago, Ill.) Morrell et al. (1975) reported that inhibition of protein synthesis by eycloheximide (CXM) was associated with failure to kindle epileptogenic lesions in frog hippocampal cortex. Ogata (1977), in rabbits, confirmed that systemic CXM blocked kindling but
E A S T E R N A S S O C I A T I O N OF EEGers c o n c l u d e d that the effect was due to anticonvulsant action of CXM rather than to protein synthesis inhibition. Our report compares the ' a n t i c o n v u l s a n t ' action of c y c l o h e x i m i d e with that of phenobarbital. Paralyzed bullfrogs were stimulated hourly in hippocampal c o r t e x as previously described. Contrary to the original study, CXM was withheld until kindling was well underway as measured by increasing A D duration and increasing n u m b e r of spontaneous epileptiform potentials (SEPs). A f t e r the 5--6th stimulation, CXM (50 mg/kg) was injected i.p. Hourly stimulation continued. F o l l o w i n g CXM the AD duration curve flattened but did not decline, i.e., further kindling was blocked but there was no interference with established A D or with threshold to electrical stimulation. In fact, SEP counts s o m e t i m e s continued to rise after CXM. In contrast, phenobarbital (30 mg/kg; blood levels, 35.0--38.0 p g / m l ) caused dramatic decrease in A D duration and abolition of SEPs. We conclude that, at least in the frog, the CXM effect is not attributable to conventional anticonvulsant action; the protein synthesis hypothesis remains tenable. (Supported in part by NIMH Grant MH24069.)
23. Electro-clinical and ultrastructural changes associated with subconvulsant doses of pentylenet e t r a z o l . - E. Rodin, M. Rodin, L. Lavine and J. Deremo (Detroit, Mich.) A variety of ultrastructural changes have been reported after convulsive seizures or focal epileptogenic lesions, leaving the question open whether they represent cause or effect. A series of rats was therefore subjected to subconvulsant and convulsant doses of p e n t y l e n e t e t r a z o l and the brains e x a m i n e d electron microscopically. A f t e r establishing baseline doses, rats were chronically implanted with cortical bipolar electrodes in frontal and parietal areas bilaterally. One week postoperatively, t h e y received on 4 successive days subconvulsant doses (10--20 mg/kg) of pentylenetetrazol. A l t h o u g h thresholds varied considerably m o r e than in cats, the following electroclinical evolution was characteristic: focal spiking in some of the sampled areas, followed by asymptomatic low voltage 'spike-wave' bursts, which were in turn followed by higher voltage, m o r e diffuse 'spikewave' bursts associated with whisker twitching. The animals were sacrificed on the fourth or fifth day before a full convulsive seizure occurred. E l e c t r o n micrographs showed increased spaces around cell structures and blood vessels suggesting cerebral edema as well as loss of neurofibrils and neurotubules. It is concluded that ultrastructural changes can be demonstrated prior to overt major seizures and with-
13P o u t damage to the cortex, as would be present in experiments dealing with topical application of convulsant agents.
24. Epileptiform seizure activity induced by antibodies to gangliosides. -- S.E. Karpiak, S.P. Mahadik and M.M. Rapport (New York, N.Y.) Intraventricular or intracortical injections of antiserum to some brain c o m p o n e n t s can induce nonclinical seizures in several animal species. A n t i s e r u m to synaptic m e m b r a n e s is particularly effective in eliciting such epileptiform activity, and it is important to establish which c o m p o n e n t s of the synaptic m e m b r a n e the antibodies are directed against. Various ganglioside structures are found in relatively high c o n c e n t r a t i o n s in synaptic membranes. We have found that antisera directed against one of these, GM1 ganglioside, are effective in inducing sustained, recurrent seizure activity, and that removal of the antibodies by specific absorption of the antiserum with pure GM1 eliminates the effect (Science, 1976). The availability and specificity of these reagents creates a potential for developing a highly reproducible m o d e l of epilepsy involving antibodies. Our m o s t recent efforts have been directed to replacing antiserum by highly purified antiganglioside antibodies prepared by affinity chromatography. A single injection of purified anti-GMl ganglioside antibodies injected into the sensorimotor c o r t e x of rats resulted, after 24 h, in focal high voltage spiking activity, initially localized but subsequently spreading both ipsilaterally and contralaterally, lasting up to 2 months. Purified a n t i b o d y appears to be more effective than antiserum since it induces abnormal discharges of greater intensity (frequency and amplitude) and longer duration.
25. Basal ganglia and limbic system aggressive seizures.-- O.J. Andy, L.P. Giurintano, S.L. Giurintano and J.W. Laing (Jackson, Miss.) The objective of the present study was to correlate the behavioral changes with the seizure patterns occurring subsequent to electrical stimulation of the basal ganglia and limbic system structures. In 13 freely moving adult cats, 840 electrically induced seizures were evaluated. Limbic and basal ganglia structures were stimulated individually and in various combinations. Hissing and growling during a seizure were considered as expressions of aggression. Interictal aggression seldom occurred. Simultaneous stimulation of two structures facilitated the d e v e l o p m e n t of aggressive seizures. Single structure stimulation was less effective. Simultaneous stimula-
14P tion of the septum and the globus pallidus was more effective than septum and amygdala. Sequential stimulations of limbic and basal ganglia structures increased the probability of inducing aggressive seizures. Limbic discharges of 10--20 c/sec and basal ganglia discharges of 2--7 c/sec which remained in isolation were not associated with aggressive behavior. In contrast, aggression occurred when a mixture of
SOCIETY PROCEEDINGS the slow basal ganglia and fast limbic frequencies simultaneously existed. Manifestations of aggression would immmediately cease if either the fast or the slow component of the after-discharge stopped. These studies suggest that simultaneous limbic and basal ganglia discharges are the neural subsystems subserving aggression associated with psychomotor seizures.
7P
© Elsevier/North-Holland Scientific Publishers, Ltd. Society proceedings EASTERN ASSOCIATION OF ELECTROENCEPHALOGRAPHERS WITH THE AMERICAN EPILEPSY SOCIETY)
(JOINT MEETING
New York City, November 29--30, 1977
Secretary-Treasurer: Dr. G. ERBA Department of Neurology, Seizure Unit, Children's Hospital Medical Center, 300 Longwood Avenue, Boston, Mass. 02115 (U.S.A.) 1. Clinical significance of the epileptogenic properties of psychotropic d r u g s . - T.M. Itil and C. Soldatos (New York, N.Y.) Neuroleptics generally increase spikes, sharp waves and paroxysmal groups in the EEG. Potently sedative neuroleptics induce epileptic activity and clinical convulsions more frequently than less sedative but extrapyramidally more effective neuroleptics. Antidepressants in higher doses may increase epileptic activity only in epileptic patients. Lithium alone has definite epileptogenic properties. Anxiolytics have antiepileptic effects, although some epileptic effects have been rarely reported. Other psychotropic drugs (reserpine, hallucinogenics, etc.) also were found epileptogenic by some authors. Epileptogenic effects depend on the convulsive properties of the drug, its dosage and the predisposition of the subject. For example, phenothiazines with aliphatic chains are more epileptogenic, whereas piperazine phenothiazines elicit minimal convulsive activity. Even less epileptogenic drugs, however, may induce epileptic activity in higher doses or with sudden changes in the dosage. The subject's convulsive threshold is most important. Individual predisposition, especially in patients with organic brain syndrome and epileptics, must be carefully considered before starting medication using EEG, medical history and neurological examination. However, psychotropic drugs in proper dosage and combined with antiepileptic medication are not contraindicated in carefully selected psychotic patients with seizures. Systematic EEG monitoring is helpful. Epileptogenic drug effects are practically negligible for subjects without low convulsive thresholds.
2. The EEG in a New York City municipal chronic disease h o s p i t a l . - - R . S . April (Roosevelt Island, N.Y.) The purpose of this report is to analyze statistically the EEGs recorded at Bird S. Coler Hospital,
an active 1246 bed municipal hospital for chronic diseases. The results of 740 consecutive EEGs during the years 1975 and 1976 will be presented with the patients' clinical diagnoses, anatomical confirmations, age and sex. Our EEG laboratory serves a unique population, the majority of whom come from ethnic and racial minorities, are at the poverty level, and suffer from chronic vascular, traumatic, degenerative, and genetic neurologic diseases. EEGs in this setting will be compared to those in published surveys from general hospitals. The differences will be described and illustrated in order to demonstrate the application and usefulness of EEG in our unique clinical population.
3. A piezoelectrical hypothesis for the origin of the alpha rhythm. -- R. Cohn (Washington, D.C. ) In an earlier study of the parametric nature of the concatenated EEG it was suggested that the alpha rhythm might be a direct result of the intermittent pressure of the blood mass on the cortical nervous net. The experimental design to develop this idea was to effect the cessation of all the blood to the brain. Initially this was attempted by unilateral vagus nerve stimulation; this method was not effective. Consequently, decapitation was employed. The electrical effect of decapitation of the gerbil forms the basis of this report. During the initial first 1/2 sec after the operation there was a remarkably decreased EEG output; this was succeeded for the next 1.5 sec by high voltage slow waves. For the next 10 sec there was a rapidly progressive decrease to zero of the electric activity. The initial 1/2 sec response was considered to be the direct effect of the cessation of intermittent pressure. The subsequent electrical activities were believed to be the result of irritative and other random agonal potential variations. The observed phenomena, although obviously not conclusive, do point to a possible piezoelectrical origin of the concatenated alpha rhythm.
8P 4. A predictor o f spike-wave bursts in petit mal EEG. - - A . Siegel, A.F. Mirsky and C.L. Grady (Boston, Mass. ) We previously r e p o r t e d a signal in pre-ictal EEG of approaching spike-wave bursts, highly successful in one patient. Pursuing this work, we have tested it on another patient, whose inter-ictal EEG is m u c h less normal. Inter-ictal fluctuations made the signals m u c h m o r e erratic in this case. It thus became necessary to test for this patient the basic hypothesis o f the existence of a feature in pre-burst EEG significantly correlated with the occurrence of bursts. We averaged spectra f r o m r a n d o m l y selected epochs of pre-bursts. T w o tendencies were observed: a decrease in energy at higher frequencies (above 10 Hz), and a more than compensating increase at lower frequencies. The quantity, energy increase at lower frequencies minus energy decrease at higher frequencies, was used as a statistic in the Wilcoxon rank-sum test; pre-burst samples outranked the others, with P < 0.0002. The procedure used was data-independent t h r o u g h o u t . It should be a straightforward m a t t e r to synthesize a pre-burst signal f r o m the above statistic, roughly as successful as that found with the first patient. The present m e t h o d is m u c h more readily adaptable to individual variations in inter-ictal EEG.
5. Periodic discharge of unusually slow character in neonatal status epilepticus caused by necrotizing encephalitis (herpes s i m p l e x ) . - F. Fineyre (Paris, France and Baltimore, Md.) An eleven-day-old n e w b o r n acutely developed the clinical s y m p t o m a t o l o g y of a CNS infection. Convulsions associated with h y p e r t h e r m i a started 3 days later. Initial EEG examinations showed no abnormalities. On the 16th day o f life, a status epilepticus with irregular and chiefly clonic convulsions materialized involving the right limbs to a greater degree. The infant was placed under massive dosages of anticonvulsants. At this stage, the EEG was severely abnormal with a periodic discharge consistently localized over the right temporal region. In the inter-ictal state, the discharge occurred at intervals of 2--4 sec, mostly against a featureless background. At the start of each seizure, ictal activity originated f r o m the right central area with repetitive spikes (about 1/sec). The slow periodic discharge over right t e m p o r a l area o f t e n persisted during the attacks. In the following, the discharge became bitemporal. Without p r o f o u n d coma, the EEG gradually flattened and the infanf died one m o n t h later. A u t o p s y c o n f i r m e d the clinical diagnosis o f herpes
SOCIETY PROCEEDINGS simplex encephalitis; there was marked necrosis in b o t h temporal lobes. This type of very slowly repetitive discharge is probably analogous to the periodic discharge of adult life herpes simplex encephalitis and differs f r o m o t h e r periodic patterns.
6. A unique EEG pattern in mucolipidosis. -- D. Bergen (Chicago, Ill.) This reports unique EEG features in a patient with mucolipidosis. A s y n d r o m e combining features of both the sphingolipidoses and the mucopolysaccharidoses has been well d o c u m e n t e d . A 19-year-old man with this disease was retarded and had generalized seizures. His EEG showed e x t r e m e l y sharp, bilateral spikes and polyspikes with striking and unusual characteristics: they usually appeared to be positive at the vertex, with a large field extending anteriorly and posteriorly parasagittally; they were n o t seen, or occurred with m u c h lower amplitude, in the temporal region. Bursts of polyspikes were often followed by slow waves but at o t h e r times occurred on the crest of such waves. These positive spikes were seen with the patient awake and asleep, and were clearly different in form and distribution from '14 and 6 positive spikes'. Spike duration was usually less than 20 msec, and some spikes were so sharp as to appear similar to muscle potentials. This pattern is entirely unlike any described previously in patients with either sphingolipidoses or mucopolysaccharidoses. It is, however, identical to that r e p o r t e d in another patient with mucolipidosis. These very sharp positive spikes may represent a unique EEG pattern which may be diagnostic for this rare disease.
7. F I R D A , periventricular edema and normal pressure hydrocephalus.--W.H. Leschey, Jr., R.C. Briggs and L.R. Altemus (Portland, Maine) A case of a 73-year-old w o m a n with typical clinical and radiological manifestations of normal pressure hydrocephalus (NPH) is presented. Pre-shunting and post-shunting psychometrics, EEGs, isotope cisternograms and CT scans are shown. The preoperative EEG consisted of f r e q u e n t frontal i n t e r m i t t e n t r h y t h m i c delta activity ( F I R D A ) bursts superimposed on a normal background. The postoperative EEG was essentially normal with no F I R D A . Analysis of the cisternographic data suggested transmural ventricular absorption of isotope. The CT scans were interpreted as showing varying degrees of periventricular edema. The reversibility of the F I R D A pattern and of the clinical and radiological signs of NPH suggests a probable significant relationship. The relevant pathophysiology of F I R D A , NPH and periventricular
EASTERN ASSOCIATION OF EEGers edema is discussed. Periventricular edema independent of pressure and ventricular size is postulated as the major factor in the production of F I R D A in obstructive hydrocephalus. Further study of F I R D A as a physiological prognosticator in NPH and clarification of the relationship with periventricular edema are needed.
8. EEG studies in hepatic encephalopathy. 'Blind' EEG evaluation. -- T. Riley, F. Fineyre, W.C. Maddrey and E. Niedermeyer (Baltimore, Md.) The treatment of 3 patients (age 32, 47 and 59 years) with advanced cirrhosis of the liver and recurrent episodes of hepatic encephalopathy was monitored by bi-weekly EEG evaluations. A total of 43 records were obtained. All patients were on a protein restricted diet (30 g/day) and were receiving lactulose (90 mg/day) throughout. The study therapies were calcium and arginine salts of ketoanalogues of branched chain amino acids. The electroencephalographers remained without information about the patient's clinical condition and therapy. In addition to visual analysis, power spectra were used occasionally. The degree of slow activity was reflected by graded abnormalities ranging from minimally to very abnormal. All 3 patients responded to the study treatment; decreased lethargy, disappearance of asterixis and improved cortical function testing were observed with treatment. In two patients, improvement and deterioration of the EEG coincided with initiation and discontinuation of treatment but EEG normalization did not materialize. The third patient had normal records between bouts of worsening but the first normalization occurred already in the state of baseline treatment (diet, lactulose). This study provides further evidence for the quick EEG response to changes of the clinical picture of hepatic encephalopathy.
9. 'Ambiguous' REM-NREM in progressive supranuclear palsy treated with L - D O P A . - C. Stafford and L. Green (Philadelphia, Pa.) A single case of progressive supranuclear palsy, treated with L-DOPA showed inter-stage sleep for prolonged periods during an all night sleep study. During these episodes, the EEG showed well formed spindles and vertex activity while striking REM and muscular atony were present. Ambiguous sleep stages have been seen frequently in narcoleptic patients, particularly on amphetamine therapy. Previous studies of sleep parameters in Steel-Richardson syndrome demonstrated suppressed REM and abnormal stage
9P 2 sleep but not ambiguous sleep. Monoamine medication may be involved in the development of prolonged inter-stage sleep.
10. Alcohol, alcoholism (New York, N.Y.)
and
epilepsy. -- R.
Jaffe
The direct relationship of alcohol ingestion to seizure and to epilepsy in general is one of the axioms of epileptology. Critical review of the literature raises serious questions as to the validity of this axiom based on limited early studies reporting high incidence of abnormal EEGs in alcoholics with seizures. Other reports derive from populations not clearly defined either clinically or electroencephalographically. There is recent evidence that 'alcoholic epilepsy' is a condition associated with a normal EEG, and without therapeutic response to phenytoin. This report presents data derived from EEGs of patients admitted for alcoholism and seizures. Out of 75 consecutive admissions in one institution, 52 EEGs were normal and 23 abnormal. Out of 33 admissions in the second institution, 28 EEGs were normal and 5 abnormal. Differences between institutions are attributable to socio-economic factors distinguishing the patient populations. None of the EEG abnormalities was characteristically 'epileptiform'; most were explained on the basis of previous head injuries, CVA, etc. The hypothesis is offered that 'alcoholic epilepsy' is a condition sui generis, and that the presumed relationship of alcohol to the illness defined as 'primary generalized epilepsy', or its manifestations, may be coincidental rather than causal. 11. Stereoelectroencephalographic (SEEG) study of five cases of primary amygdalo-hippocampal epilepsy. -- J.-M. Saint-Hilaire, G. Bouvier, A. Leduc and G. Bouillon (Montreal, Canada) A very precise system has been developed to record clinical epileptic seizures from scalp and depth electrodes, to allow exact anatomical, electrical and clinical correlations (Un. reed. Can., 1976, 105: 1538--1541, and Epilepsia, 1977, 18: 285). We studied 5 cases of primary amygdalo-hippocampal seizures; 3 from the hippocampus and 2 from the amygdala. To differentiate primary involvement of the amygdala from the hippocampus, we have studied various parameters: (1) interictal slow and epileptiform activity recorded from scalp and depth electrodes, (2) ictal activity during numerous spontaneous seizures, (3) results of electrical stimulation, and (4) detailed clinical analysis of spontaneous seizures and of symptoms induced by electrical stimulation.
]0P In primary hippocampal epilepsy, EEG slow activity tends to appear more diffusely over the involved hemisphere and epileptic activity takes a bilaterally synchronous form, p r e d o m i n a t i n g over the involved hemisphere. In primary epilepsy of the amygdala, the epileptic and slow activities are m o r e localized to the corresponding t e m p o r a l lobe. In the depth, hippocampal epilepsy gives rise to ictal activity which spreads more diffusely, particularly to the cingulate and frontal cortex. Clinically, the study of s p o n t a n e o u s seizures and electrical stimulation showed that 'fear' and ' c h e w i n g ' probably originate in the amygdala while 'nausea' comes from the hippocampus.
12. A m i n o acid levels in 3/see spike-wave epilepsy. -N. Aslam, J.D. Metrackos, K. Metrackos and N.J. Van Gelder (Montreal, Canada) The mean serum levels o f 14 free amino acids from 14 patients with 3/sec spike-wave epilepsy were compared with 22 controls. The m e a n values for certain simple and c o m p o u n d ratios of these acids were also compared. Statistically significant differences, some at the 0.001% levels, were o b t a i n e d f r o m 4 o f the 3 amino acids tested and for 4 of the ratios. On the basis of the amino acid levels alone and e m p l o y i n g a m o d i f i c a t i o n of the Walker index for multivariant analysis, it has been possible to separate the epileptics f r o m the controls with a very high degree of reliability. The possible neurobiochemical significance o f these findings, particularly in reference to aspartic acid, glutamic acid and taurine will be discussed.
13. A microprocessor device for data acquisition and averaging of brain stem auditory r e s p o n s e s . R.G. Bickford, D.A. Brittain, K.R. Hanson and D.S. Karnaze (La Jolla, Calif.) Brain stem evoked response techniques (far-field) have rapidly established their clinical value in the diagnosis o f neuronal m a t u r a t i o n in the newborn and a variety of a u d i t o r y and brain stem lesions in older patients. Since this technique is frequently used in the nursery and the ICU with ill or c o m a t o s e patients, there is need for specially designed, c o m p a c t equipm e n t for easy use under these difficult environmental circumstances. The ' E R A ' (evoked response averager) system has been designed specifically for o p e r a t i o n under these conditions. It consists of the following modules contained in a single carrying case weighing 34 lb (15.5 kg): (a) click generator with stepwise dB intensity adjustment; (b) stimulus c o u n t e r ; (c) elect r o d e impedance tester; (d) bioamplifiers of a p p r o -
SOCIETY PROCEEDINGS priate band pass ( 1 0 0 - - 3 0 0 0 Hz); (e) amplitude editor (manual or a u t o m a t i c ) for suppression of 'overload artifact'; (f) microprocessor (Intel 8080) unit for response averaging; (g) oscilloscope for display of EEG or accumulating average during the e x p e r i m e n t ; (h) manually movable cursor for amplitude and latency measures. The system works with a small separate m i n i p l o t t e r (Simpson) w h e n a hard copy or superimposed traces are required. Testing in normal subjects and patients has shown excellent utility of the system under trying conditions of the emergency r o o m , ICU, and nursery. Examples of its clinical application will be shown.
14. Automatic high speed detection of human sleep variables using a hardware pre-processor.- R. Broughton, D. Green, O. Sherif, J. Mary and B. da Costa (Ottawa, Canada) A hybrid approach has been chosen to perform high speed, automatic, inexpensive analysis of h u m a n sleep. It combines a hardware pre-processor to detect E E G polygraphic events with subsequent staging by a microprocessor. Recordings c o m e f r o m a m b u l a n t subjects using portable 4-channel recorders permitting acquisition of 24 h of data on one cassette. Playback and detection is at 20x recording speed. Only those variables essential for h u m a n sleep staging are detected. Their accuracy is c o m p a r e d to multiple (3) blind h u m a n scoring. Alpha r h y t h m is detected by a circuit using a phase-locked loop (PLL) which gives an analogue pulse for presence or absence of a 8--12.5 c/sec, over 20 pV, more or less sinusoidal, activity from a referential occipital-ear derivation. Concordance with consensus h u m a n scoring to these criteria was 92%. Spindles are detected by a similar PLL circuit for 11.5--15 c/sec, over 25 pV, sinusoidal bursts, lasting 0.5 sec or more, in a central-ear derivation: concordance was 85%. K c o m p l e x e s are detected with 91% c o n c o r d a n c e by a m a t c h e d filter approach, based on a charge-coupled device. Delta activity is detected by baseline crossing and period analysis, s u p p l e m e n t e d by an amplitude criterion, for 0.3--2.5 c/sec, over 75/2V activity and c o n c o r d e d 92%. REMs and muscle t o n e are also detected.
15. Brain stem auditory evoked responses: normal variations in humans and utility of monaural stimulation in clinical neurology. --K.H. Chiappa and K.S. Gladstone (Boston, Mass.) In brain stem auditory evoked responses (BAER), the I, III and IV--V waves are the ones m o s t comm o n l y used for evaluation of possible abnormalities
EASTERN ASSOCIATION OF EEGers in patiens. BAERs were recorded from 50 normal subjects. Six different patterns of the wave IV--V complex and 2 forms of wave III were recognized. About half the subjects had similar wave forms in both ears; the other half had dissimilar wave forms, although the degree of dissimilarity was usually less than that seen between different subjects. Repeat recordings, in some subjects over up to 1 year, showed these patterns to remain essentially unchanged. Masking white noise in the unstimulated ear changed the shape of the IV--V complex. Monaural stimulation is also often useful in clinical neurological cases (examples of this will be shown).
16. Somatosensory evoked far-field potentials in patients with multiple sclerosis.- B.J. Anziska, R.Q. Cracco, A.W. Cook and E. Feld (Brooklyn, N.Y.) Somatosensory evoked far-field potentials to separate stimulation of the left and right median nerves were recorded from the scalp of 15 normal subjects and 26 patients with definite multiple sclerosis (McAlpine's criteria). In normal subjects these farfield potentials consist of 3 positive potentials thought to arise in subcortical regions including the brain stem and diencephalon, followed by a negative potential which is thought to reflect the arrival of the afferent volley in cerebral cortical elements. The criteria for abnormality in the patient group were (a) absence of components consistently recorded in normal subjects, and (b) statistically significant component peak latency differences in patients compared to controls. Over 80% of the patients were judged to be abnormal based on these criteria. Most of the patients had absence of some component(s) consistently recorded in normal subjects. Sequential recordings obtained in 4 patients revealed loss or appearance of components or latency changes. Significant alterations in the evoked potentials were observed in some of these patients in the absence of apparent clinical change. It seems that this method will prove useful in the evaluation of some patients with brain stem and diencephalic dysfunction.
17.Deviant topography of somatosensory evoked potentials in s c h i z o p h r e n i a . - G. Shagass, R.A. Roemer, J.J. Straumanis and M. Amadeo (Philadelphia., Pa. ) In studies aimed at establishing evoked potential (EP) correlates of psychiatric illness, the topographic dimension has hitherto received little attention. We
11P present here results obtained by comparing somatosensory (SEP) topography in schizophrenics, nonpsychotic psychiatric patients, and non-patients matched for age and sex (25 in each group). Patients were free of drugs for a median of 10 days. Right and left median nerves were stimulated with 0.1 msec duration pulses 10 mA above sensory threshold. SEPs were recorded from 14 scalp leads and an EOG lead (linked ear reference). Successive SEP peaks were visually detected with a cursor program in the contralateral post-central leads; their latencies were stored and used to measure amplitudes automatically in all leads at these latencies. Spatial distributions of individual peaks were plotted and amplitude differences between groups were compared by multivariate analysis of variance and profile analysis. The main findings showed significant posterior displacement of P30 and N60 peaks in the schizophrenic patients, compared to non-psychotic patients and controls; topographies were similar in the latter two groups. Deviant SEP topography in chronic schizophrenics appears to parallel the posteriorly displaced regional cerebral blood flow reported in such patients by other investigators.
18. EEG changes with seizures induced by immunologic assault in the rat. - - J . G . Franke, V.A. Lennon, C.S. Selzor and R.G. Bickford (La Jolla, Calif. ) The occurrence of generalized and focal seizures was observed in the course of hyperacute autoimmune allergic encephalomyelitis (HEAE) experiments in the rat (V. Shorn, Neurosci. Abstr., 1976: 19). Additional experiments now define the model. Thirteen Lewis rats were prepared as follows: (a) 5 rats were injected with guinea pig myelin basic protein; (b) 3 rats were adrenalectomized and then treated by passive transfer of 'activated lymphocytes' from HEAE rats; (c) 5 rats were treated as controls for the above procedures. In all animals, EEG was recorded with skull screws and low noise cable before, during, and after procedures with spectral estimates (CSA). (1) The normal rat EEG shows considerable change with behavior, and many sharp transients and 'epileptiform patterns' are observed. (2) Rats developing clinical seizures show significant spectral changes in the pre-seizure period. (3) The animals with clinical seizures show florid focal and generalized patterns including diffuse synchronized spike and wave. (4) Seizure activity occurred in all animals of groups (a) and (b). Now seizures or significant discharges occurred in control animals. This immunologic model of epilepsy in the rat is of current interest in view of reported findings of
12P immunologic abnormalities in patients with constitutional type of epilepsy.
19. Effects o f changes in cortical excitability upon the spike and wave bursts in generalized penicillin epilepsy o f the cat. -- A. Pellegrini and P. Gloor (Montreal, Canada) Previous studies had suggested that the spike and wave bursts of feline generalized epilepsy represent the response of hyperexcitable cortex to thalamocortical volleys normally evoking spindles. If this were the ease, it should be possible to convert spike and wave bursts in generalized penicillin epilepsy into spindles by decreasing the excitability of cortical neurons. Cortical excitability was decreased (a) by hypoxia, (b) by topical application to the cortex of KC1, (c) GABA, or (d) barbiturates. During generalized penicillin epilepsy, KC1 induced spreading depression and hypoxia abolished spike and wave bursts which were replaced by spindles. Topical application of GABA or of barbiturates reduced or inverted the negative spikes of the spike and wave complexes, while augmenting the negative slow waves, or revealing them clearly when they had been poorly developed. This effect is probably due to selective inactivation of the superficial cortical layers. These results are compatible with the hypothesis that spike and wave complexes are induced by corticopetal volleys normally involved in spindle genesis. This is further supported by the fact that if spindles and spike and waves occurring in the same animal are compared, a direct correlation between the frequencies of these two rhythms can be demonstrated.
20. 'Drop epileptic seizures': atonic, tonic, myoclonic components ; clinical and electrophysiological c o r r e l a t e s . - C.T. Lombroso and G. Erba (Boston, Mass.) By utilizing techniques of continuous EEG, video, and at times EMG monitoring, we have analyzed closely a group of epileptic patients in whom 'drop seizures' were common. We observed a spectrum of clinical manifestations ranging from single or repetitive head drops, to whole body akinesia, mixed on some occasions with what appear myoclonic or tonic manifestations. Concomitant EEG discharges varied from bursts of slow waves or spike waves to fast recruiting rhythms or a combination of the three. Fast recruiting discharges very often accompanying major atonic seizures could not be distinguished from those accompanying a tonic seizure. Likewise, spikewave bursts during an atonic head drop did not appear different from those occurring in absences
SOCIETY PROCEEDINGS with or without head bobbing or with tonic upward deviation of the eyes. It appears that opposite peripheral phenomena such as paroxysmal increase or decrease in tonic muscular activity may be accompanied by similar EEG correlates. Thus, EEG discharges alone, although always generalized and synchronous, are in these cases not specific for various ictal phenotypes. A subcortical, possibly brain stem origin, might explain the above variability in EEG and peripheral ictal phenomena implying now excitatory, now inhibitory influences upon spinal m o t o r function.
21. Computed EEG topography (CET) of paroxysmal and background activity in seizure d i s o r d e r s . R.N. Harner and K.A. Ostergren (Philadelphia, Pa.) Computed EEG topography (CET) is a new method that displays individual waves according to their amplitude, duration, and channel of origin, producing a quasi-anatomical 'head'. and stores data for off-line display or computation. The CET retains and quantifies much information that is useful for clinical EEG interpretation ( E l e c t r o e n c e p h . clin. N e u r o p h y s i o l . , 1977, 42: 721). However, the real test of such a method is its applicability to the study of epilepsy. During 8 months, 45 CETs obtained from persons referred for seizures were interpreted independently of the routine EEG or the clinical history. CET findings in 21 cases with underlying gross lesion included focal abnormalities in 17, paroxysmal features in 10 (1 bilateral spike-wave) and focal depression of background activity in 11. In 10 cases with focal seizures and no gross lesion, 9 CETs were focal, 8 paroxysmal (1 bilateral spike-wave) and no instance of focal depression, In 14 non-focal cases, the CET showed focal spikes in 2, bilateral paroxysmal features in 8 (7 spike-wave), and no focal depression. The CET retains significant information concerning the nature and location of EEG disturbances in epilepsy. A combination of visual display and quantitative output effectively summarizes that information for clinical use.
22. Cycloheximide suppression of kindling is not an anticonvulsant effect. -- E. Kessler, E. Moneta and F. Morrell (Chicago, Ill.) Morrell et al. (1975) reported that inhibition of protein synthesis by eycloheximide (CXM) was associated with failure to kindle epileptogenic lesions in frog hippocampal cortex. Ogata (1977), in rabbits, confirmed that systemic CXM blocked kindling but
E A S T E R N A S S O C I A T I O N OF EEGers c o n c l u d e d that the effect was due to anticonvulsant action of CXM rather than to protein synthesis inhibition. Our report compares the ' a n t i c o n v u l s a n t ' action of c y c l o h e x i m i d e with that of phenobarbital. Paralyzed bullfrogs were stimulated hourly in hippocampal c o r t e x as previously described. Contrary to the original study, CXM was withheld until kindling was well underway as measured by increasing A D duration and increasing n u m b e r of spontaneous epileptiform potentials (SEPs). A f t e r the 5--6th stimulation, CXM (50 mg/kg) was injected i.p. Hourly stimulation continued. F o l l o w i n g CXM the AD duration curve flattened but did not decline, i.e., further kindling was blocked but there was no interference with established A D or with threshold to electrical stimulation. In fact, SEP counts s o m e t i m e s continued to rise after CXM. In contrast, phenobarbital (30 mg/kg; blood levels, 35.0--38.0 p g / m l ) caused dramatic decrease in A D duration and abolition of SEPs. We conclude that, at least in the frog, the CXM effect is not attributable to conventional anticonvulsant action; the protein synthesis hypothesis remains tenable. (Supported in part by NIMH Grant MH24069.)
23. Electro-clinical and ultrastructural changes associated with subconvulsant doses of pentylenet e t r a z o l . - E. Rodin, M. Rodin, L. Lavine and J. Deremo (Detroit, Mich.) A variety of ultrastructural changes have been reported after convulsive seizures or focal epileptogenic lesions, leaving the question open whether they represent cause or effect. A series of rats was therefore subjected to subconvulsant and convulsant doses of p e n t y l e n e t e t r a z o l and the brains e x a m i n e d electron microscopically. A f t e r establishing baseline doses, rats were chronically implanted with cortical bipolar electrodes in frontal and parietal areas bilaterally. One week postoperatively, t h e y received on 4 successive days subconvulsant doses (10--20 mg/kg) of pentylenetetrazol. A l t h o u g h thresholds varied considerably m o r e than in cats, the following electroclinical evolution was characteristic: focal spiking in some of the sampled areas, followed by asymptomatic low voltage 'spike-wave' bursts, which were in turn followed by higher voltage, m o r e diffuse 'spikewave' bursts associated with whisker twitching. The animals were sacrificed on the fourth or fifth day before a full convulsive seizure occurred. E l e c t r o n micrographs showed increased spaces around cell structures and blood vessels suggesting cerebral edema as well as loss of neurofibrils and neurotubules. It is concluded that ultrastructural changes can be demonstrated prior to overt major seizures and with-
13P o u t damage to the cortex, as would be present in experiments dealing with topical application of convulsant agents.
24. Epileptiform seizure activity induced by antibodies to gangliosides. -- S.E. Karpiak, S.P. Mahadik and M.M. Rapport (New York, N.Y.) Intraventricular or intracortical injections of antiserum to some brain c o m p o n e n t s can induce nonclinical seizures in several animal species. A n t i s e r u m to synaptic m e m b r a n e s is particularly effective in eliciting such epileptiform activity, and it is important to establish which c o m p o n e n t s of the synaptic m e m b r a n e the antibodies are directed against. Various ganglioside structures are found in relatively high c o n c e n t r a t i o n s in synaptic membranes. We have found that antisera directed against one of these, GM1 ganglioside, are effective in inducing sustained, recurrent seizure activity, and that removal of the antibodies by specific absorption of the antiserum with pure GM1 eliminates the effect (Science, 1976). The availability and specificity of these reagents creates a potential for developing a highly reproducible m o d e l of epilepsy involving antibodies. Our m o s t recent efforts have been directed to replacing antiserum by highly purified antiganglioside antibodies prepared by affinity chromatography. A single injection of purified anti-GMl ganglioside antibodies injected into the sensorimotor c o r t e x of rats resulted, after 24 h, in focal high voltage spiking activity, initially localized but subsequently spreading both ipsilaterally and contralaterally, lasting up to 2 months. Purified a n t i b o d y appears to be more effective than antiserum since it induces abnormal discharges of greater intensity (frequency and amplitude) and longer duration.
25. Basal ganglia and limbic system aggressive seizures.-- O.J. Andy, L.P. Giurintano, S.L. Giurintano and J.W. Laing (Jackson, Miss.) The objective of the present study was to correlate the behavioral changes with the seizure patterns occurring subsequent to electrical stimulation of the basal ganglia and limbic system structures. In 13 freely moving adult cats, 840 electrically induced seizures were evaluated. Limbic and basal ganglia structures were stimulated individually and in various combinations. Hissing and growling during a seizure were considered as expressions of aggression. Interictal aggression seldom occurred. Simultaneous stimulation of two structures facilitated the d e v e l o p m e n t of aggressive seizures. Single structure stimulation was less effective. Simultaneous stimula-
14P tion of the septum and the globus pallidus was more effective than septum and amygdala. Sequential stimulations of limbic and basal ganglia structures increased the probability of inducing aggressive seizures. Limbic discharges of 10--20 c/sec and basal ganglia discharges of 2--7 c/sec which remained in isolation were not associated with aggressive behavior. In contrast, aggression occurred when a mixture of
SOCIETY PROCEEDINGS the slow basal ganglia and fast limbic frequencies simultaneously existed. Manifestations of aggression would immmediately cease if either the fast or the slow component of the after-discharge stopped. These studies suggest that simultaneous limbic and basal ganglia discharges are the neural subsystems subserving aggression associated with psychomotor seizures.
