Focal seizures due to chronic localized encephalitis Theodore Rasmussen, M.D., Jerzy Olszewski, M.D.' and Donald Lloyd-Smith, M.D. OCCASIONALSPECIMENS of scarred, atrophic Remooal of the left frontal lobe, carded out six brain removed for the relief of focal cerebral months after the onset of seizures in a fruitless at- seizures at the Montreal Neurological Institute tempt to stop them, proofded an oppoctunity to compare the miczoscopic picture at that time with have shown striking perivascular collections that shown at autopsy three and a half months of round cells, particularly in less severely later. damaged areas of these specimens. In the past Birth and early development of this child were this perivascular cuffing has been attributed normal, and there were no signscant illnesses until April 1955 at 18 months of age, when the parents to the effect on the brain of recurring seiz- noted a scratch behind the right ear. The follow- ures, with recognition, however, that this was ing day swelling in this region was noted and the a rather unsatisfactory explanation since the temperature rose to 104" F. The tempefature sub- great majority of surgical specimens removed sided the next day after administration of penicil- from patients with equally frequent focal seiz- lin, but the swelling behind the ear continued to discharge bloody fluid for one week. ures do not show this change. Histologic The child seemed entirely well for two months, studies of surgical specimens from three chil- but in July he became unusually irritable one day dren recently operated upon for intractable and vomited the followin mornin . That after- focal seizures suggest that this microscopic noon he seemed dizzy an% soon aifer was noted to stare and salivate; he then developed clonic picture may indicate the presence of an un- movements of the right side of the body. suspected, more or less localized, chronic en- Thejerkin? conic seizure soon became generalized and cephalitis that has smoldered along over a persisted for an hour before the convulsion was period of years. The clinical and histologic stopped by administration of chloroform. data on these three children will be reported A similar attack occurred a month later in August 1955, and from then on milder right-sided in some detail. seizures recurred several times daily. During the The most complete study from the patho- next three months his usual quiet, pleasant be- logic standpoint was made in the last of the behavior changed and he became somewhat irrita- three patients to appear. This case will be dis- ble and destructive. During this period his parents felt that his speech was becoming somewhat less cussed first, since it seems to clarify interpreta- clear than it had been. tion of the train of events in the other two. In November the right arm became completely useless and hung limply by his side for three days. CASE REPORTS From the department of neurology and neurosurgery. Mc- Case 1. An 18 month old boy deoeloped seiz- Gill University end the Montreal Neurological Institute, ures following an infected scratch behind the right Montreal. Quebec, Canada. .Present address: Laboratoly of Experimental New- ear. Focal right-sided seizures became increasingly pathology. College of Medicine, University of Saskatche- frequent, despite maximal doses of anticonwlsants. wan, Saskatoon, Cunnda. 435 436 NEUROLOGY c3.p, 1_. :"~,~,;.,"~/-.,~.,,.~.=.~-~ -. .. II- l.~ ,f:"Sfi\p&/7"J\h\n p3.01Pi? L'4L.;7*,, ,+.,A .' .- * -.** ,"%'.I.. ,",~.~d*,L."i.l,/.+. "\'.',, -.. L/ TA.cl ~~~,~.~,~~~.~~";~,..f2 -;, -'bL''.+O .b'w\&L-V Cz-T3 I FIG. 1. Case 1. Sample from an electroencephalo- gram made during the first week in hospital. Hori- zontal scale indicates 1 second, vertical scale repre- sents 100 microvolts. FIG. 3. Case 1. Sections fr 111 autopsy. A. Right frontal lobe, Nissl stain, 5% B. Left frontal lobe, Nissl stain, 55x. C. Left cuiieus. Nissl stain. 165,. D. Left frontal lobe, Nissl stain, 400x. FIG. 4. Case 1. Sections from autopsy. A. Left cu- FIG. 2. Case 1. Surgical specimen from left frontal neus. hematoxylin-phloxin-safranin stain, 55x. B. Left lobe. A. Nissl stain, 165x. B. Nissl stain, 400x. central region, gold chloride sublimate impregnation. C. Nissl stain. 55x. D. Cold chloride sublimate im- 400x. C. Right central region, gold chloride subli- pregnation, 16.5~. mate impregnation, 400x. Strength then returned in the arm, but his gait rectal1 failed to control the seizures which re- gradually became unsteady. currecreach time as he awakened. Between at- He was admitted to the Montreal Neurological tacks, however, he was able to play with his toys Institute December 8, 1955, five months after his if not too heavily medicated. first seizure. He was a cooperative two year old The sli ht right hemiparesis gradually became boy, talking and playing normally between fre- more mar1 ed. On January 10, 1956, six months quent ma'or and minor right-sided seizures. There after the onset, he was operated upon and the was a sligkt but definite right hemiparesis. He was right frontal lobe was removed in a futile effort somewhat dehydrated, but once that was corrected to interrupt the almost daily episodes of status the urinalysis and white blood cell count were nor- epilepticus which were thought to be producing mal. There was a moderatel severe hypochromic the slowly progressive hemiparesis. The cortex ap- anemia. The spinal fluid finiings were normal, as peared grossly normal, but the cortical electroen- were skull and chest roentgenograms and a pneu- cephalogram showed epileptiform activity through- moencephalogram. out the entire exposed area, most marked anterior- An electroencephalogram showed widespread ly. The postoperative cortical electroencephalo- slow-wave abnormalities from both sides of the gram showed the epileptiform abnormality persist- head, with frequent seizure discharges in the left ing unchanged in the central and parietal regions. frontocentral region ( figure 1 ) . Seizures recurred as he awakened from the anes- The patient continued to have many right-sided thetic and continued as before operation. A post- seizures daily, despite maximal doses of Dilantin, operative electroencephalogram two weeks later enobarbital, Tridione, Mysoline, Mesantoin, and showed the same diffuse slow-wave abnormality ghromides. At times paraldehyde was necessary to as before, with most marked epileptiform activity stop episodes of status epilepticus. Sleep for sev- in the left central region. Bromides, administered eral hours each day induced with Avertin given until the blood level reached 280 mg. per cent, FOCAL SEZZURES DUE TO CHRONIC ENCEPHALlTZS 437 lessened the attacks little if at all. Kee ing the of the convexities and basal ganglia of the two child aslee with paraldehyde was the os y effec- cerebral hemispheres, cerebellum, pons, and me- tive way oP sto ping the attacks. For several weeks dulla and stained by both tinctorial and metallic he was allowexto wake up two or three times each methods. day to eat but he often vomited his meals with Sections from the right hemisphere were nor- a seizure; it finally became necessary to feed him mal, except for the presence of a few small round by stomach tube while he was asleep in order to cells in the erivascular spaces around some of the maintain ad uate nutrition. His course had been larger VesseTs and occasional round cells in the quite afebril?before operation and during the first leptomeninges ( figure 3A ) . two postoperative months. In March 1956 saliva- Sections from the left hemisphere showed in- tion with the seizures became an increasing prob- tensive perivascular cuffing by round cells in both lem. Despite the tracheotomy which was carried the cortex and white matter in all areas, similar out at this time, it was diEcult to keep his lun s to that seen in the surgical specimen (figure 3B). clear. The seizures continued, his eneral conk There were numerous di&se and patchy areas of tion gradually deteriorated, and he %ied April 24, infiltration of the cortex and white matter by in- 1956, three and one-half months after operation flammatory cells, predominantly microglia and and nine months after his first seizure. small round cells with occasional polymorphonu- The initial spinal fluid examination in Decem- clear cells (figure 3C and D). Red cells were ber 1955 showed 3 cells per cu.mm. and 18 mg. numerous in all regions, especially in the cortex. per cent protein. Because histologic examination Numerous areas showed laminar loss of nerve cells of the surgical specimen removed in January 1956 in the fifth and sixth layers, with spongy degen- showed evidence of encephalitis (figure 2). the eration (figure 4A). The astrocytes were hyper- cerebrospinal fluid was examined periodically dur- trophied and increased in number as compared ing his postoperative course, startine four weeks with the right hemisphere (figure 4B and C). after operation when it was felt that any pleoc - There was a similar but less marked inflamma- tosis due to the operation itself would have sug- tory process in the basal ganglia on the left, while sided completely. Weekly examinations in Feb- the corresponding region on the right was normal, ruary, four to eight weeks after operation, showed except for the presence of a few compound gran- 20 to 55 white cells per cu. mm., mainly polymor- ular corpuscles and an occasional round cell phonuclear cells in the first two specimens and around a few of the larger vessels. mainly mononuclear cells in the next three speci- The pons, medulla, and cerebellum were nor- mens. The protein levels varied from 66 to 98 mal, except for the presence of a few inflamma- mg. per cent. The colloidal gold curve on Febru- tory cells in the leptomeninges and a slight reduc- ary 29 was 255543200. In March, two months tion in number of the Purkinje cells.