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Epilepsia , 2&23S 245, 1979.
Raven Press, New York
Chronic Cerebellar Stimulation in the Treatment of Epilepsy Laurence F. Levy and William C. Auchterlonie Department of Surgery, University of Rhodesia, Salisbury ZimbabwelRhodesia
Summary: Six cases of intractable epilepsy who were subjected to chronic cerebellar stimulation are reported. They had all been treated with a wide range of anticonvulsant drugs without success. The ages varied between 17 and 55 years. Three were genetic-inherent, 2 were of unknown etiology, and 1 was symptomatic (infection? trauma?). Four had generalized major convulsions and 2 had a mixture of major and minor attacks, 1 with a strong temporal lobe component. Stimulation was commenced in all cases as soon as the patient had a postoperative seizure. Headache occurred in all cases and necessitated reduction in the strength of the stimulation to between 2 and 4 V in all cases except 1. Occipital nerve block temporarily relieved 1 patient, but posterior root section of C2-C3 and part of C4 did not prevent headaches in another case. Two patients were greatly improved and managed to hold employment whereas formerly they had been unemployed. One patient felt 50% improved but there was no reduction in his seizure frequency; another had a 50% reduction in seizures but felt no better. One patient was noted to be improved intellectually although her seizures were more frequent. The remaining patient was unchanged. One patient committed suicide and another drowned. One prosthesis became infected and had to be removed.
Chronic cerebellar stimulation in the treatment of epilepsy was introduced by Cooper in 1973. Since that time he has reported 32 cases, 18 of whom showed a good response (Cooper et al., 1976). Dow et al. (1977) reported 3 further cases all of whom were improved although 1 case did not start stimulation for 18 months after surgery because of intervening spontaneous remission of seizures. Fenton et al. (1977) reported 1 partially improved case. We report 6 further cases. These were all intractable epileptics who had been treated with a wide range of anticonvulsant drugs
without success. They were all subjected to a complete psychiatric, psychological, neuroradiological, and electroencephalographic evaluation prior to being offered the treatment. The proposed therapy was explained to each patient and the relatives as an unproven but rationally valid procedure. Being very extensively disabled by the disorder, each of these patients consented readily. CASE REPORTS Case no. I: D. M., male, aged 55 at operation on September 4, 1974. There was no
Received February 21, 1978. Key words: Epilepsy-Cerebellar stimulation-Case review.
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relevant family or personal history. Etiology, genetic-inherent? He had suffered severe and frequent major and minor seizures since childhood, wore a crash helmet constantly as a child, and had his education considerably interrupted by this condition. Five years previously he had fractured his skull in a seizure. His seizures, which were now almost entirely nonfocal generalized major convulsions, lasted a few minutes and occurred approximately 12 times per year. He was as well controlled by phenobarbital, 30 mg t.i.d., and diazepam, 2 mg t.i.d., as by any other of the drugs he had tried which included phenytoin, primidone, carbamazepine, and sulthiame in varying doses and combinations. His preop. EEGs had shown considerable variation but had often shown typical spikeand-wave paroxysms with diffuse background slowing in the theta range (Fig. 1). Cerebellar stimulation was commenced when he suffered his first postop. seizure 10 days after surgery. Initially, stimulation at 10 V and 10ds was applied to each side alternately for 1 hr each, but after 1 month this was changed to 8 min on and off for each side and reduced progressively to 3 V. The patient developed bilateral occipital headaches at the higher voltages but these disappeared on the left side when the stimulation was reduced to 3 V, although they remained on the right side. It became necessary to discontinue stimulation there after 1 month, continuing only with the left side. It was restarted on the right side after 3 months at low intensity, and he now stimulates both sides at 3 V at 10 c/s with slight right-sided pain. In the 20 months prior to surgery he had suffered 20 seizures; for more than the last 20 months he has been free of all attacks and is now regularly employed. His EEG is improved although some slowing and mildly paroxysmal activity is seen (Fig. 2). Case no. 2: M. B., male, aged 19 at the time of operation on March 19, 1976. Seizures commenced at the age of 9 months.
Epilepsia, Vol. 20, June 1979
There was no relevant personal or family history. Etiology unknown. The attacks consisted of nonfocal generalized major convulsions of a few minutes duration and minor episodes of petit ma1 type. Over the years, he had been treated with phenobarbital, phenytoin, primidone, methoin, diazepam, folic acid, and cyanocobalamine. His preop. medication was ethosuximide, 250 mg t.i.d.; carbamazepine, 200 mg t.i.d.; and sodium valproate, 200 mg t.i.d. IQ was 68. Repeated EEGs showed abnormal diffusely slow activity with a tendency toward paroxysms with maximum slowing on the left side, especially the left temporal region (Fig. 3). Stimulation was begun 8 days after the operation at 3 V and 10 c/s alternately to each side for 8 min when he had his first postoperative seizure, and it has remained at that strength. Unfortunately, after some months the receiver on the right side began to erode through the skin. A number of attempts were made to close this but it had to be removed on May 19, 1977, at which time the wires to the left side were damaged. An EEG performed on September 4, 1977 confirmed this. Stimulation was therefore effectively discontinued at the end of May 1977, even though the patient continued to stimulate until September. In the 15 months prior to his operation he had suffered 15 major and 127 minor seizures. In the 15 months from the time of commencement to cessation of the stimulation, he suffered a total of 13 aborted (using the jam button), 2 major, and 25 minor seizures. His medication is unaltered. He now holds a clerical job having been unemployed prior to his operation. It will be important to see what happens now that the stimulation has been discontinued. However, he has only had five minor seizures in the past 3 months. His EEG is basically the same as preoperatively but appears slightly improved (Fig. 4). Case no. 3: .E. W . , female, aged 35, at operation on December 21, 1974. Seizures started at the age of 13%. There was no
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CHRONIC CEREBELLAR STIMULATION relevant family or personal history. Etiology unknown. She had sustained a fractured skull and a fractured odontoid process and had had many plastic procedures undertaken on her head and face for injuries sustained during her attacks. She had suffered from a variety of seizures, sometimes as generalized major convulsions, sometimes generalized with a strong temporal lobe element, and sometimes minor. She took phenobarbital, 30 mg t.i.d., and phenytoin, 100 mg t.i.d., having previously been treated with primidone, carbamazepine, sodium valproate, sulfthiame, troxidone, methoin, ethosuximide, methsuximide and phensuximide, amitriptyline, diazepam, and diamox in varying doses and combinations. Her EEGs had always shown slow activity and spikes which appeared persistently in the left posterior temporal region but which were considered too widespread for cortical resection, becoming paroxysmal at times (Fig. 5). Stimulation at 8 V and 10 c/S was commenced 25 days after operation, but the patient discontinued it after 8 months due to headache and because she became depressed by what she considered a failure. All. voltages from 1- 10 had been tried. It was uncertain that the headache was related to stimulation. On May 20, 1975, an attempt was made to alter the position of the stimulating electrodes because of headache. This had to be abandoned owing to scarring around the wires which would have been damaged by further efforts to release them. In the 8 months before operation she had suffered 135 major and 263 minor seizures. In the 8 months following operation while stimulating she suffered 72 major and 220 minor seizures. It would seem worthwhile restarting the stimulation routine and possibly she would yield to differing frequencies. Postoperatively, her EEG is substantially unchanged (May 27, 1975). Case no. 4: L.G., female, aged 18 at operation on March 2, 1976. Attacks started at the age of 5 years. There was no relevant
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personal or family history. Etiology, genetic-inherent? The seizures were generalized nonfocal major convulsions of varying frequency and severity. Medication was phenytoin, 50 mg,five times daily and primidone, 250 mg, five times daily, prior to which she had been treated with phenobarbital, ethosuximide, carbamazepine, sulfthiame, troxidone, diamox, and diazepam in varying doses and combinations. EEGs had shown generalized slowing with frequent bilateral paroxysms of high voltage delta, theta, and spikes anteriorly. (Fig. 6). Psychiatric evaluation had shown her to be a passive and amenable personality who was contented and loving but excessively dependent. It was held that without her mother’s care she would have had to be institutionalized. In July 1975, the psychologist observed that he had tested her in 1970 when her IQ score was 75 but that she had deteriorated intellectually in the 5 years since that time. He commented, “From L.’s point of view I cannot recommend that she is a suitable case for the introduction of a stimulator. She could not manipulate the controls satisfactorily and would have little appreciation of their significance. The only positive aspect would be to relieve her mother of the stress of constant nursing care.” For this latter reason, a stimulator was inserted. Stimulation was begun 10 days postoperatively at 8 V and 10 c/s. It was necessary to reduce stimulation to 3.5 V at 10 c/s after 1 month as above this level she had some tingling and headaches. She was reviewed by the psychologist on August 4, 1976. He stated, “In half the areas measured some advance is recorded while in five measures the presenting picture is unchanged. In only one area a negligible drop is recorded. Although I gather that her seizure pattern is virtually unchanged, she is certainly more alert and better able to communicate than was the case a year ago. In consequence my negative 1975 recommendation is only partially supported.” In the 11 months before operaEpilepsia, Vol. 20, June 1979
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CHRONIC CEREBELLAR S TIMULAT I 0N tion she suffered 49 major convulsions and 435 minor seizures. In the 11 months after operation she had 85 major and 395 minor seizures, and possibly different stimulation parameters are required here. Her EEG (November 29, 1976) remained abnormal, slow, and paroxysmal but showed a slight overall improvement over the preoperative tracings (Fig. 7). Case no. 5: F. van R., male, aged 31 at operation on February 3, 1976. When 18 months old, he experienced a loss of consciousness which lasted over a day. He started to have generalized major convulsions at the age of 7 years. There was no relevant personal or family history. Etiology, symptomatic? postinflammatory? posttraumatic? From 7 until 15, he suffered attacks once per week although occasionally they would be as frequent as five or six times per day. At 17, his IQ was 89. He was prone to episodes of depression and temper tantrums not apparently related to his epilepsy. His medication was primidone, 250 mg t.i.d., and he had also been treated with phenobarbital, phenytoin, benzedrine, and carbamazepine in various doses and combinations. EEG showed overall diffuse slowing maximum in the left anterior temporal area but never localized enough for cortical resection to be considered (Fig. 8). Stimulation was started on February 18, 1976, at 8 V and 10 c/s, but the patient varied this considerably without recording it, and an absolutely accurate record is not available. He suffered some headaches during stimulation, despite the fact that the posterior roots of C2, C3, and part of C4 had been sectioned at the time of insertion of the stimulator in an effort to prevent the occurrence of headaches, and stimulation was reduced to 4.5 V. He committed suicide -in a fit of depression by shooting himself through the head on September 9, 1976. Only a few days before this, he had reported that he thought himself 50% improved, although this was not apparent on his seizure score postoperatively. It was
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always difficult to determine exactly how many seizures this patient had, but in the few months prior to the operation they were definitely known to have occurred at least once per month, sometimes severe, sometimes mild. Postoperatively he had suffered 20 major convulsions and six minor seizures in 7 months and he looked well. At autopsy a scar was seen on the inferior surface of the left temporal gyrus. His postoperative EEGs had been unchanged. Case no. 6: V. B., female, aged 17 at operation on February 18, 1975. Seizures commenced at 11 years of age. There was no relevant personal or family history apart from asthma. Etiology, inherent-genetic? Seizures consisted of major generalized convulsions and minor attacks. Psychological testing showed that intellectually she was in the lower average range. Psychiatric assessment showed no disorder apart from mild anxiety which was thought to be contributory to the frequency of her seizures. Postoperatively, however, she developed a mild and brief psychotic reaction. Her medication was sulthiame, 50 mg t.i.d., and carbamazepine, 200 mg t.i.d., and she had also been treated with phenobarbital, phenytoin, primidone, troxidone, ethosuximide, paramethadione, diazepam, diamox, amitriptyline, rivrotril, and sodium valproate. Repeated EEGs had shown diffuse theta and delta activity with typical and atypical episodes of paroxysmal spike and wave at 3-3% c/s (Fig. 9). Stimulation was commenced 10 days postoperatively at 10 c/s and 3 V alternating from side to side every 8 min. This was reduced to 1 V and later increased to 2.25 v. The patient was only able to continue until December 11, 1976, when, complaining of headaches which were probably not related to her stimulation, she abandoned treatment. She was reassessed in September 1976 by the psychologist who observed that “the theoretical aspects of her psychograph are virtually unchanged but on the practical plane she is functioning at a lower level and Epilepsia, Vol. 20, June 1979
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is less perceptive of human emotion than previously.” Nonetheless, she managed to complete her training as a draughtswoman and held a job in a tolerant environment. Her medication of sulthiame and carbamazepine was unchanged. In the 10 months prior to her operation she suffered seven major and an uncountable number of minor seizures. In the 10 months after operation she suffered 12 major and many minor seizures. On June 1, 1977, she suffered a seizure and died in her bath. Her EEG was basically unchanged. Alterations in Medication We have not altered the medication in any of the patients. Complications Infection occurred in case no. 2 and it was ultimately necessary to remove the entire prosthesis. All 6 of our patients qomplained of headaches but the etiology was difficult to determine. They varied from localized to generalized, and in case no. 1 they came on only when the stimulator switched to the right side and were relieved by occipital nerve blockade. However, a posterior root section of C2 and C3 performed in case no. 5 at the time of insertion of the stimulator did not prevent the occurrence. They were an alleged cause for discontinuing stimulation in 2 cases but were always controllable by reducing the stimulator voltage.
effect since other psychological methods (hypnotism) had been tried in the past and had failed. One other patient, however, felt 50% improved but had no reduction in the frequency of his attacks-surely a placebo effect-and another (case no. 4) seemed brighter intellectually-possibly this is also placebo. One patient was somewhat improved in that she had 50% reduction in her major attacks although she felt no better and discontinued therapy. However, she seems a suitable candidate for stimulation at other frequencies. The remaining patient was unaffected; indeed, she seemed deteriorated. However, it does not seem likely that this deterioration was caused by stimulation. It is not possible, on the basis of these results, to prognosticate as to who might and who might not be improved, but it would seem worthwhile to persist with the therapy in selected patients and to attempt to vary the parameters of stimulation. In the 2 patients who have died, there did not appear to be gross damage to the cerebellum although further investigation along these lines will be required. ACKNOWLEDGMENT I would like to thank Mr. Roger Avery of Avery Electronics, Farmingdale, Long Island, New York for the kind gift of two of these stimulators, and the State Lotteries Trustees of Zimbabwe Rhodesia for the gift of three others.
REFERENCES DISCUSSION Cooper IS. Chronic stimulation of paledcerebellar cortex in man. Lancet 1:206, 1973. Out of 6 intractable patients, 2 have Cooper IS et al. Chronic cerebellar stimulation in shown marked improvement and have beepilepsy. Arch Neurol33:559-570, 1976. come viable units. Whether they will con- Dow RS et al. Proc. Western EEG SOC.,EEG and Clin. Neurophysiol, vol. 43, no. 6, p. 906, Dec. tinue to be so in the future remains to be 1977. seen, but their long histories suggest that Fenton GW et al. Chronic cerebellar stimulation in the treatment of epilepsy. Eighth International they would not have been so improved Epilepsy Symposium, JK Penry (Ed), Raven Press, without this treatment. It is of course posNew York. sible that the placebo effect has been enough to influence these 2 (it is a dramatic R I ~ S U M I ~ treatment with continuing physician interSix kpileptiques (Ages de 17 A55 ans) dont les crises est), but it seems unlikely to be such an rksistaient aux mkdicaments anticonvulsifs ont ktk Epilepsia, Vol. 20, June 1979
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CHRONIC CEREBELLAR STIMULATION soumis & la stimulation cerebelleuse chronique. Trois cas etaient genktiques, un cas symptomatique (trauma ou infection?) Et deux cas d’etiologie inconnue. Quatre avaient des convulsions gkneraliskes majeures e t deux une association de crises majeures et mineures, dont un avec une forte composante temporale. La stimulation fut entreprise dbs la survenue de la premibre crise postoptratoire. Des ckphalbes sont apparues dans tous les cas, n6cessitant une reduction de I’intensite de la stimulation de 2 4 volts, sauf dans un cas. Chez un patient les ckphalees ont et6 temporairement supprimees par le “blocage” du nerf occipital, mais dans un autre cas elles persisterent malgrb la section des racines postdrieures de C2-C3 et d‘une partie de C4. Deux malades ont 6t6 considdrablement amkliorks et purent se procurer un emploi. Un autre se sentait amelior6 B 50% alors qu’il n’y avait aucune reduction de ses crises, tandis qu’un autre avait ses crises rkduites de 50% mais ne se sentait pas mieux pour cela. L’avant-dernibr malade ttait jug6 intellectuellernent amklior6 alors que ses crises 6taient plus Mquentes. Le dernier malade enfin ne prksentait aucune modification de son &at. Un des malades s’est suicide et un autre s’est noye. Dans un cas la prothbse s’est infectee et a d0 &treenlevee.
paciente. Dos pacientes mejoraron en gran medida y fueron capaces de mantener un empleo (aunque con anterioridad estaban desempleados). Un paciente se sinti6 mejorado en un 50%, a pesar de que no hubo una reduccibn en el ndmero de sus crisis. Otro sujeto tuvo una reducci6n del 50% de sus crisis, pero no se sinti6 mejorado. El resto de 10s pacientes no sufri6 variaciones. Un paciente se suicid6 y otro murib ahogado. Una de las pr6tesis se infect6 y hubo de ser quitada. (A. Portera Sanchez, Madrid)
ZUSAMMENFASSUNG
Bericht iiber 6 F U e therapieresistenter Epilepsie, die zur chronischen zerebelliiren Stimulierung iiberwiesen waren. Alle waren erfolglos mit einer grokn Anzahl Antikonvulsiva behandelt worden. Ihr Alter schwankte zwischen 17 und 55 Jahren. 3 zeigten eine genetische Belastung, 2 eine unbekannte Ktiologie, 1 Patient geh6rte in die symptomatische Gruppe (fragliche Infektion, fragliches Trauma). 4 Patienten hatten generalisierte groBe Anfiille und 2 eine Kombination grokr und kleiner Anfillle, I mit starker Beteiligung des Temporallappens. Die Stimulierung wurde in allen (J.-L. Gastaut, Marseilles) FUen dann begonnen, wenn der Patient ein postoperativen Anfall hatte. Kopfschmerzen traten bei allen Patienten auf und verursachten eine Reduktion RESUMEN der Stiirke der Stimulation auf zwischen 2 und 4 Volt Se presentan seis pacientes con epilepsia intratable bei allen Patienten mit einer Ausnahme. Eine vorque fueron sometidos a estimulaci6n cerebelosa Ilbergehende Blockade des Occipitalnerven fiihrte zur cr6nica. Estos enfermos habian sido tratados con Verminderung der Beschwerden bei einem Patienten anticonvdsivantes sin 6xito. Tres sujetos padecian aber die Sektion der Hinterwurzeln CZC3 und von epilepsia geneticehereditaria, dos tenian epilepsia de Teilen von C4 konnten sie in einem anderen Fall nicht causa desconocida y en un caso las crisis eran verhiiten. 2 Patienten wurden stark gebessert und secundarias (tinfeccibn? ttrauma?). Cuatro tenian konnten besch$iftigt werden, wiihrend sie frtiher keine crisis generalizadas mayores y dos tenian una mezcla Anstellung hatten. 1 Patient fUhlte sich um 50% gebesde crisis mayores y menores, uno de ellos con un sert, zeigte aber keine Reduktion seiner Anfallshiiufigfuerte componente del 16bulo temporal. En todos 10s keit, wiihrend ein anderer eine 5O%ige Reduktion casos se comenz6 la estimulaci6n tan pronto como seiner Anfallshiiufigkeit bot, sich aber nicht besser 10s pacientes sufrieron una crisis comicial despubs fiihlte. Bei einer Patientin wurde eine intellektuelle de la operaci6n. En todos 10s pacientes surgieron Verbesserung bemerkt , obwohl ihre Anfiille zahlcefaleas y se precis6 reducir la fuerza del estimulo reicher geworden waren. Der letzte Patient blieb unhasta 2-4 voltios, except0 en un caso. Un bloqueo veriindert. Ein Patient beging Selbstmord, ein anderer del nervio occipital hizo mejorar temporalmente a un ertrank. Ein Implantat infizierte sich und mube entenfermo per0 la secci6n de las rakes posteriores fernt werden. (D. Scheffner, Heidelberg) C2, C3, y parte de C4 no hizo mejorar a otro
Epilepsia, Vol. 20, June 1979
Epilepsia , 2&23S 245, 1979.
Raven Press, New York
Chronic Cerebellar Stimulation in the Treatment of Epilepsy Laurence F. Levy and William C. Auchterlonie Department of Surgery, University of Rhodesia, Salisbury ZimbabwelRhodesia
Summary: Six cases of intractable epilepsy who were subjected to chronic cerebellar stimulation are reported. They had all been treated with a wide range of anticonvulsant drugs without success. The ages varied between 17 and 55 years. Three were genetic-inherent, 2 were of unknown etiology, and 1 was symptomatic (infection? trauma?). Four had generalized major convulsions and 2 had a mixture of major and minor attacks, 1 with a strong temporal lobe component. Stimulation was commenced in all cases as soon as the patient had a postoperative seizure. Headache occurred in all cases and necessitated reduction in the strength of the stimulation to between 2 and 4 V in all cases except 1. Occipital nerve block temporarily relieved 1 patient, but posterior root section of C2-C3 and part of C4 did not prevent headaches in another case. Two patients were greatly improved and managed to hold employment whereas formerly they had been unemployed. One patient felt 50% improved but there was no reduction in his seizure frequency; another had a 50% reduction in seizures but felt no better. One patient was noted to be improved intellectually although her seizures were more frequent. The remaining patient was unchanged. One patient committed suicide and another drowned. One prosthesis became infected and had to be removed.
Chronic cerebellar stimulation in the treatment of epilepsy was introduced by Cooper in 1973. Since that time he has reported 32 cases, 18 of whom showed a good response (Cooper et al., 1976). Dow et al. (1977) reported 3 further cases all of whom were improved although 1 case did not start stimulation for 18 months after surgery because of intervening spontaneous remission of seizures. Fenton et al. (1977) reported 1 partially improved case. We report 6 further cases. These were all intractable epileptics who had been treated with a wide range of anticonvulsant drugs
without success. They were all subjected to a complete psychiatric, psychological, neuroradiological, and electroencephalographic evaluation prior to being offered the treatment. The proposed therapy was explained to each patient and the relatives as an unproven but rationally valid procedure. Being very extensively disabled by the disorder, each of these patients consented readily. CASE REPORTS Case no. I: D. M., male, aged 55 at operation on September 4, 1974. There was no
Received February 21, 1978. Key words: Epilepsy-Cerebellar stimulation-Case review.
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relevant family or personal history. Etiology, genetic-inherent? He had suffered severe and frequent major and minor seizures since childhood, wore a crash helmet constantly as a child, and had his education considerably interrupted by this condition. Five years previously he had fractured his skull in a seizure. His seizures, which were now almost entirely nonfocal generalized major convulsions, lasted a few minutes and occurred approximately 12 times per year. He was as well controlled by phenobarbital, 30 mg t.i.d., and diazepam, 2 mg t.i.d., as by any other of the drugs he had tried which included phenytoin, primidone, carbamazepine, and sulthiame in varying doses and combinations. His preop. EEGs had shown considerable variation but had often shown typical spikeand-wave paroxysms with diffuse background slowing in the theta range (Fig. 1). Cerebellar stimulation was commenced when he suffered his first postop. seizure 10 days after surgery. Initially, stimulation at 10 V and 10ds was applied to each side alternately for 1 hr each, but after 1 month this was changed to 8 min on and off for each side and reduced progressively to 3 V. The patient developed bilateral occipital headaches at the higher voltages but these disappeared on the left side when the stimulation was reduced to 3 V, although they remained on the right side. It became necessary to discontinue stimulation there after 1 month, continuing only with the left side. It was restarted on the right side after 3 months at low intensity, and he now stimulates both sides at 3 V at 10 c/s with slight right-sided pain. In the 20 months prior to surgery he had suffered 20 seizures; for more than the last 20 months he has been free of all attacks and is now regularly employed. His EEG is improved although some slowing and mildly paroxysmal activity is seen (Fig. 2). Case no. 2: M. B., male, aged 19 at the time of operation on March 19, 1976. Seizures commenced at the age of 9 months.
Epilepsia, Vol. 20, June 1979
There was no relevant personal or family history. Etiology unknown. The attacks consisted of nonfocal generalized major convulsions of a few minutes duration and minor episodes of petit ma1 type. Over the years, he had been treated with phenobarbital, phenytoin, primidone, methoin, diazepam, folic acid, and cyanocobalamine. His preop. medication was ethosuximide, 250 mg t.i.d.; carbamazepine, 200 mg t.i.d.; and sodium valproate, 200 mg t.i.d. IQ was 68. Repeated EEGs showed abnormal diffusely slow activity with a tendency toward paroxysms with maximum slowing on the left side, especially the left temporal region (Fig. 3). Stimulation was begun 8 days after the operation at 3 V and 10 c/s alternately to each side for 8 min when he had his first postoperative seizure, and it has remained at that strength. Unfortunately, after some months the receiver on the right side began to erode through the skin. A number of attempts were made to close this but it had to be removed on May 19, 1977, at which time the wires to the left side were damaged. An EEG performed on September 4, 1977 confirmed this. Stimulation was therefore effectively discontinued at the end of May 1977, even though the patient continued to stimulate until September. In the 15 months prior to his operation he had suffered 15 major and 127 minor seizures. In the 15 months from the time of commencement to cessation of the stimulation, he suffered a total of 13 aborted (using the jam button), 2 major, and 25 minor seizures. His medication is unaltered. He now holds a clerical job having been unemployed prior to his operation. It will be important to see what happens now that the stimulation has been discontinued. However, he has only had five minor seizures in the past 3 months. His EEG is basically the same as preoperatively but appears slightly improved (Fig. 4). Case no. 3: .E. W . , female, aged 35, at operation on December 21, 1974. Seizures started at the age of 13%. There was no
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CHRONIC CEREBELLAR STIMULATION relevant family or personal history. Etiology unknown. She had sustained a fractured skull and a fractured odontoid process and had had many plastic procedures undertaken on her head and face for injuries sustained during her attacks. She had suffered from a variety of seizures, sometimes as generalized major convulsions, sometimes generalized with a strong temporal lobe element, and sometimes minor. She took phenobarbital, 30 mg t.i.d., and phenytoin, 100 mg t.i.d., having previously been treated with primidone, carbamazepine, sodium valproate, sulfthiame, troxidone, methoin, ethosuximide, methsuximide and phensuximide, amitriptyline, diazepam, and diamox in varying doses and combinations. Her EEGs had always shown slow activity and spikes which appeared persistently in the left posterior temporal region but which were considered too widespread for cortical resection, becoming paroxysmal at times (Fig. 5). Stimulation at 8 V and 10 c/S was commenced 25 days after operation, but the patient discontinued it after 8 months due to headache and because she became depressed by what she considered a failure. All. voltages from 1- 10 had been tried. It was uncertain that the headache was related to stimulation. On May 20, 1975, an attempt was made to alter the position of the stimulating electrodes because of headache. This had to be abandoned owing to scarring around the wires which would have been damaged by further efforts to release them. In the 8 months before operation she had suffered 135 major and 263 minor seizures. In the 8 months following operation while stimulating she suffered 72 major and 220 minor seizures. It would seem worthwhile restarting the stimulation routine and possibly she would yield to differing frequencies. Postoperatively, her EEG is substantially unchanged (May 27, 1975). Case no. 4: L.G., female, aged 18 at operation on March 2, 1976. Attacks started at the age of 5 years. There was no relevant
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personal or family history. Etiology, genetic-inherent? The seizures were generalized nonfocal major convulsions of varying frequency and severity. Medication was phenytoin, 50 mg,five times daily and primidone, 250 mg, five times daily, prior to which she had been treated with phenobarbital, ethosuximide, carbamazepine, sulfthiame, troxidone, diamox, and diazepam in varying doses and combinations. EEGs had shown generalized slowing with frequent bilateral paroxysms of high voltage delta, theta, and spikes anteriorly. (Fig. 6). Psychiatric evaluation had shown her to be a passive and amenable personality who was contented and loving but excessively dependent. It was held that without her mother’s care she would have had to be institutionalized. In July 1975, the psychologist observed that he had tested her in 1970 when her IQ score was 75 but that she had deteriorated intellectually in the 5 years since that time. He commented, “From L.’s point of view I cannot recommend that she is a suitable case for the introduction of a stimulator. She could not manipulate the controls satisfactorily and would have little appreciation of their significance. The only positive aspect would be to relieve her mother of the stress of constant nursing care.” For this latter reason, a stimulator was inserted. Stimulation was begun 10 days postoperatively at 8 V and 10 c/s. It was necessary to reduce stimulation to 3.5 V at 10 c/s after 1 month as above this level she had some tingling and headaches. She was reviewed by the psychologist on August 4, 1976. He stated, “In half the areas measured some advance is recorded while in five measures the presenting picture is unchanged. In only one area a negligible drop is recorded. Although I gather that her seizure pattern is virtually unchanged, she is certainly more alert and better able to communicate than was the case a year ago. In consequence my negative 1975 recommendation is only partially supported.” In the 11 months before operaEpilepsia, Vol. 20, June 1979
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CHRONIC CEREBELLAR S TIMULAT I 0N tion she suffered 49 major convulsions and 435 minor seizures. In the 11 months after operation she had 85 major and 395 minor seizures, and possibly different stimulation parameters are required here. Her EEG (November 29, 1976) remained abnormal, slow, and paroxysmal but showed a slight overall improvement over the preoperative tracings (Fig. 7). Case no. 5: F. van R., male, aged 31 at operation on February 3, 1976. When 18 months old, he experienced a loss of consciousness which lasted over a day. He started to have generalized major convulsions at the age of 7 years. There was no relevant personal or family history. Etiology, symptomatic? postinflammatory? posttraumatic? From 7 until 15, he suffered attacks once per week although occasionally they would be as frequent as five or six times per day. At 17, his IQ was 89. He was prone to episodes of depression and temper tantrums not apparently related to his epilepsy. His medication was primidone, 250 mg t.i.d., and he had also been treated with phenobarbital, phenytoin, benzedrine, and carbamazepine in various doses and combinations. EEG showed overall diffuse slowing maximum in the left anterior temporal area but never localized enough for cortical resection to be considered (Fig. 8). Stimulation was started on February 18, 1976, at 8 V and 10 c/s, but the patient varied this considerably without recording it, and an absolutely accurate record is not available. He suffered some headaches during stimulation, despite the fact that the posterior roots of C2, C3, and part of C4 had been sectioned at the time of insertion of the stimulator in an effort to prevent the occurrence of headaches, and stimulation was reduced to 4.5 V. He committed suicide -in a fit of depression by shooting himself through the head on September 9, 1976. Only a few days before this, he had reported that he thought himself 50% improved, although this was not apparent on his seizure score postoperatively. It was
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always difficult to determine exactly how many seizures this patient had, but in the few months prior to the operation they were definitely known to have occurred at least once per month, sometimes severe, sometimes mild. Postoperatively he had suffered 20 major convulsions and six minor seizures in 7 months and he looked well. At autopsy a scar was seen on the inferior surface of the left temporal gyrus. His postoperative EEGs had been unchanged. Case no. 6: V. B., female, aged 17 at operation on February 18, 1975. Seizures commenced at 11 years of age. There was no relevant personal or family history apart from asthma. Etiology, inherent-genetic? Seizures consisted of major generalized convulsions and minor attacks. Psychological testing showed that intellectually she was in the lower average range. Psychiatric assessment showed no disorder apart from mild anxiety which was thought to be contributory to the frequency of her seizures. Postoperatively, however, she developed a mild and brief psychotic reaction. Her medication was sulthiame, 50 mg t.i.d., and carbamazepine, 200 mg t.i.d., and she had also been treated with phenobarbital, phenytoin, primidone, troxidone, ethosuximide, paramethadione, diazepam, diamox, amitriptyline, rivrotril, and sodium valproate. Repeated EEGs had shown diffuse theta and delta activity with typical and atypical episodes of paroxysmal spike and wave at 3-3% c/s (Fig. 9). Stimulation was commenced 10 days postoperatively at 10 c/s and 3 V alternating from side to side every 8 min. This was reduced to 1 V and later increased to 2.25 v. The patient was only able to continue until December 11, 1976, when, complaining of headaches which were probably not related to her stimulation, she abandoned treatment. She was reassessed in September 1976 by the psychologist who observed that “the theoretical aspects of her psychograph are virtually unchanged but on the practical plane she is functioning at a lower level and Epilepsia, Vol. 20, June 1979
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is less perceptive of human emotion than previously.” Nonetheless, she managed to complete her training as a draughtswoman and held a job in a tolerant environment. Her medication of sulthiame and carbamazepine was unchanged. In the 10 months prior to her operation she suffered seven major and an uncountable number of minor seizures. In the 10 months after operation she suffered 12 major and many minor seizures. On June 1, 1977, she suffered a seizure and died in her bath. Her EEG was basically unchanged. Alterations in Medication We have not altered the medication in any of the patients. Complications Infection occurred in case no. 2 and it was ultimately necessary to remove the entire prosthesis. All 6 of our patients qomplained of headaches but the etiology was difficult to determine. They varied from localized to generalized, and in case no. 1 they came on only when the stimulator switched to the right side and were relieved by occipital nerve blockade. However, a posterior root section of C2 and C3 performed in case no. 5 at the time of insertion of the stimulator did not prevent the occurrence. They were an alleged cause for discontinuing stimulation in 2 cases but were always controllable by reducing the stimulator voltage.
effect since other psychological methods (hypnotism) had been tried in the past and had failed. One other patient, however, felt 50% improved but had no reduction in the frequency of his attacks-surely a placebo effect-and another (case no. 4) seemed brighter intellectually-possibly this is also placebo. One patient was somewhat improved in that she had 50% reduction in her major attacks although she felt no better and discontinued therapy. However, she seems a suitable candidate for stimulation at other frequencies. The remaining patient was unaffected; indeed, she seemed deteriorated. However, it does not seem likely that this deterioration was caused by stimulation. It is not possible, on the basis of these results, to prognosticate as to who might and who might not be improved, but it would seem worthwhile to persist with the therapy in selected patients and to attempt to vary the parameters of stimulation. In the 2 patients who have died, there did not appear to be gross damage to the cerebellum although further investigation along these lines will be required. ACKNOWLEDGMENT I would like to thank Mr. Roger Avery of Avery Electronics, Farmingdale, Long Island, New York for the kind gift of two of these stimulators, and the State Lotteries Trustees of Zimbabwe Rhodesia for the gift of three others.
REFERENCES DISCUSSION Cooper IS. Chronic stimulation of paledcerebellar cortex in man. Lancet 1:206, 1973. Out of 6 intractable patients, 2 have Cooper IS et al. Chronic cerebellar stimulation in shown marked improvement and have beepilepsy. Arch Neurol33:559-570, 1976. come viable units. Whether they will con- Dow RS et al. Proc. Western EEG SOC.,EEG and Clin. Neurophysiol, vol. 43, no. 6, p. 906, Dec. tinue to be so in the future remains to be 1977. seen, but their long histories suggest that Fenton GW et al. Chronic cerebellar stimulation in the treatment of epilepsy. Eighth International they would not have been so improved Epilepsy Symposium, JK Penry (Ed), Raven Press, without this treatment. It is of course posNew York. sible that the placebo effect has been enough to influence these 2 (it is a dramatic R I ~ S U M I ~ treatment with continuing physician interSix kpileptiques (Ages de 17 A55 ans) dont les crises est), but it seems unlikely to be such an rksistaient aux mkdicaments anticonvulsifs ont ktk Epilepsia, Vol. 20, June 1979
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CHRONIC CEREBELLAR STIMULATION soumis & la stimulation cerebelleuse chronique. Trois cas etaient genktiques, un cas symptomatique (trauma ou infection?) Et deux cas d’etiologie inconnue. Quatre avaient des convulsions gkneraliskes majeures e t deux une association de crises majeures et mineures, dont un avec une forte composante temporale. La stimulation fut entreprise dbs la survenue de la premibre crise postoptratoire. Des ckphalbes sont apparues dans tous les cas, n6cessitant une reduction de I’intensite de la stimulation de 2 4 volts, sauf dans un cas. Chez un patient les ckphalees ont et6 temporairement supprimees par le “blocage” du nerf occipital, mais dans un autre cas elles persisterent malgrb la section des racines postdrieures de C2-C3 et d‘une partie de C4. Deux malades ont 6t6 considdrablement amkliorks et purent se procurer un emploi. Un autre se sentait amelior6 B 50% alors qu’il n’y avait aucune reduction de ses crises, tandis qu’un autre avait ses crises rkduites de 50% mais ne se sentait pas mieux pour cela. L’avant-dernibr malade ttait jug6 intellectuellernent amklior6 alors que ses crises 6taient plus Mquentes. Le dernier malade enfin ne prksentait aucune modification de son &at. Un des malades s’est suicide et un autre s’est noye. Dans un cas la prothbse s’est infectee et a d0 &treenlevee.
paciente. Dos pacientes mejoraron en gran medida y fueron capaces de mantener un empleo (aunque con anterioridad estaban desempleados). Un paciente se sinti6 mejorado en un 50%, a pesar de que no hubo una reduccibn en el ndmero de sus crisis. Otro sujeto tuvo una reducci6n del 50% de sus crisis, pero no se sinti6 mejorado. El resto de 10s pacientes no sufri6 variaciones. Un paciente se suicid6 y otro murib ahogado. Una de las pr6tesis se infect6 y hubo de ser quitada. (A. Portera Sanchez, Madrid)
ZUSAMMENFASSUNG
Bericht iiber 6 F U e therapieresistenter Epilepsie, die zur chronischen zerebelliiren Stimulierung iiberwiesen waren. Alle waren erfolglos mit einer grokn Anzahl Antikonvulsiva behandelt worden. Ihr Alter schwankte zwischen 17 und 55 Jahren. 3 zeigten eine genetische Belastung, 2 eine unbekannte Ktiologie, 1 Patient geh6rte in die symptomatische Gruppe (fragliche Infektion, fragliches Trauma). 4 Patienten hatten generalisierte groBe Anfiille und 2 eine Kombination grokr und kleiner Anfillle, I mit starker Beteiligung des Temporallappens. Die Stimulierung wurde in allen (J.-L. Gastaut, Marseilles) FUen dann begonnen, wenn der Patient ein postoperativen Anfall hatte. Kopfschmerzen traten bei allen Patienten auf und verursachten eine Reduktion RESUMEN der Stiirke der Stimulation auf zwischen 2 und 4 Volt Se presentan seis pacientes con epilepsia intratable bei allen Patienten mit einer Ausnahme. Eine vorque fueron sometidos a estimulaci6n cerebelosa Ilbergehende Blockade des Occipitalnerven fiihrte zur cr6nica. Estos enfermos habian sido tratados con Verminderung der Beschwerden bei einem Patienten anticonvdsivantes sin 6xito. Tres sujetos padecian aber die Sektion der Hinterwurzeln CZC3 und von epilepsia geneticehereditaria, dos tenian epilepsia de Teilen von C4 konnten sie in einem anderen Fall nicht causa desconocida y en un caso las crisis eran verhiiten. 2 Patienten wurden stark gebessert und secundarias (tinfeccibn? ttrauma?). Cuatro tenian konnten besch$iftigt werden, wiihrend sie frtiher keine crisis generalizadas mayores y dos tenian una mezcla Anstellung hatten. 1 Patient fUhlte sich um 50% gebesde crisis mayores y menores, uno de ellos con un sert, zeigte aber keine Reduktion seiner Anfallshiiufigfuerte componente del 16bulo temporal. En todos 10s keit, wiihrend ein anderer eine 5O%ige Reduktion casos se comenz6 la estimulaci6n tan pronto como seiner Anfallshiiufigkeit bot, sich aber nicht besser 10s pacientes sufrieron una crisis comicial despubs fiihlte. Bei einer Patientin wurde eine intellektuelle de la operaci6n. En todos 10s pacientes surgieron Verbesserung bemerkt , obwohl ihre Anfiille zahlcefaleas y se precis6 reducir la fuerza del estimulo reicher geworden waren. Der letzte Patient blieb unhasta 2-4 voltios, except0 en un caso. Un bloqueo veriindert. Ein Patient beging Selbstmord, ein anderer del nervio occipital hizo mejorar temporalmente a un ertrank. Ein Implantat infizierte sich und mube entenfermo per0 la secci6n de las rakes posteriores fernt werden. (D. Scheffner, Heidelberg) C2, C3, y parte de C4 no hizo mejorar a otro
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