CLINICAL ELECTROENCEPHALOGRAPHY
31 NO 4
Correlation Between Clinical Stages and EEG
Findings of Subacute Sclerosing Panencephalitis
'Candan GOrses, Aylln OztOrk, BetOI Baykan, Anen Gokylglt,
Mefkure Eraksoy, Meral Barlas, Ahmet Call,kan and Hlfzl Ozean
KeyWords
Electroencephalography
Periodic Complexes
Spike and Wave Discharges
Subacute Sclerosing Panencephalitis
INTRODUCTION
Subacute sclerosing panencephalitis (SSP E), as
described by Dawson in1933, isan inflammatory and degen-
erative disease ofthe central nervous system. The etiological
agent ofSSPE was not known before 1969. The isolation of
the measles virus from brain cell cultures ofpatients with
SSPE has been as important as the description ofthe dis-
ease.' The onset ofSSPE isinsidious. Mental and behavioral
changes are subtle atthe beginning. Myoclonus and head
drops are the most clinically significant signs for SSPE, and
hemiplegia, deafness, severe behavioral changes, demen-
tia, visual and speech involvement may also be detected. The
course ofthe illness isslowly orsometimes rapidly progres-
sive, and the clinical presentation may be autonomic failure,
vegetative state and mutism.
There seems to be a higher prevalence inwhites and
among rural populations. Forevery 100,000cases ofmeasles
that occur naturally worldwide, there are 0.6 to2.2 cases of
SSPE. 2 SSPE usually results indeath within 1to3years. The
outcome may vary; 5to9% have spontaneous partial orcom-
plete remissions.'
Periodic high amplitude slow wave complexes inthe EEG,
first described by Radermeckerl and Cobb and Hills are one of
the main diagnosticcriteria inthis disease, inspite ofthe vari-
ability ofEEG findings during the course ofthe disease.
Although the measles vaccination isadministered without
charge inour country, SSPE isstill seen but with adecreasing
trend. The purpose ofour study istodetermine the relation-
ship between the clinical stages ofthe disease and both the
typical and atypical EEG findings.
SUBJECTS AND METHODS
Inthis retrospective study, allclinical histories and the
EEG recordings of67 patients that were admitted tothe hos-
pital with the diagnosis of SSPE between 1980 and 1998
were reviewed. Using the criteria ofSSPE diagnosis (clinical
signs, characteristic EEG patterns, high titres of measles
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201
<02006 VOL.
antibodies inthe serum and CSF), the patients were divided
into two groups. Group Afulfilled allcriteria. However, due to
the inability tomeasure measles antibody before 1987, it
was not possible toobserve the third criterion inGroup B. In
the latter group, before the diagnosis was established,
patients had been examined by serial EEGs until the charac-
teristic EEG patterns appeared. Brain biopsy was required for
the diagnosis inonly 1 patient. Atotal of 204 EEGs were
examined according tothe clinical stages. During admission
the patients had more than 1EEG, and the interval between
EEGs ranged from 2to21 days. Video EEG monitoring was
donefor5 patients.
Among 67 patients, groups Aand Bconsisted of51 boys
and 16 girls ranging inage between 1to23 years, mean age
13.1. The male/female ratio was 3:1.All patients were classi-
fied according totheir clinical stages, by combining and mod-
ifying the two earlierclassifications forthe stages ofSSPE3.8
using our classification as follows: Stage 1A. Mild mental
and/orbehavioral changes; Stage 1B. Marked mental and/or
behavioral changes (enough to impair communication);
Stage 2A. Myoclonus and/or other involuntary movements
and epileptic seizures; Stage 2B. Focal deficits (speech dis-
orders, 1055ofvision and limb weakness); Stage 2C. Marked
involuntary movements, severe myoclonus orfocal deficits
enough toimpair full dailyactivities; Stage 3.Akinetic mutism,
vegetative state, decerebrate and decorticate rigidity, coma;
Stage 4.Remission; and Stage 5. Relapse. The stages ofall
patients are shown inTable 1.
Scalp EEG recordings were done forallpatients using the
International 10-20 System with 8, 12 and 16channel instru-
ments. Both bipolar and monopolar recordings were done. A
paperspeed of30 mm/sec was utilized butduring hyperventi·
lation and photic stimulation 15mm/sec was used. Since 1995
digital EEG systems have been used. The sensitivity ofEEG
recording was setat100IN/cm and filters at0.5 and 70Hz.
From the Department 01 Neurology, Istanbul Faculty 01 Medicine, Universi-
tyoflstanbul.
Presented inpartattheAmerican Epilepsy Society Meeting, December 3-8,
1999. Orlando. Florida.
Requests forreprints should beaddressed toDr. Candan GUOl8S, University
01 Istanbul, Istanbul Faculty ofMedicine, Department 01 Neurology, Millet
Caddesi 34390, Istanbul Tur1ley.
CLINICAL ELECTROENCEPHALOGRAPHY C2000 VOL. 31 NO 4

Table 1
Sixty-seven patients with SSPE
Stage 1A 1B 2A 2B 2C 3
GroupA 1 1 12 7 11 6
GroupB 2 0 14 5 6 2
Total 3 1 26 12 17 8

Fp2-F4

'-------

Fp1-F3 -------r---'-

F3·C3 ...------~-_.------------...------""""'.../"'....

C3-P3 -----------~~-------.,,,./-------

P3-01~~"""'w'
""'.........."""'-----......,~-,.,,"""'.~
,."'"¥""......~ •
...........~-------'"
f
50.,VL-
1 •• c
Figure 1.
Amplitude asymmetry, PC over the right hemisphere, and low amplitude delta activity over anterior regions ofboth hemispheres (1 By / M/
stage2A).

RESULTS beginning but 47 days later it was synchronous. Only 1of

The most characteristic finding inthe EEGs ofthe patients
with SSPE was periodic complexes (PC), which appeared in
high amplitude and generalized forms often showing fre-
quent recurrences. The mean PC amplitude was 174.47 ±
37.85 ~V; noPC amplitude difference was found between the
two groups. The mean duration ofPC was 1.63 sec. (0.48-
7.24) and the interval between the PCs was 11.49 sec. (2.18-
58.9). There was nostatistically significant difference
between groupsAand Bbased on the other EEG findings. In
stage 1,4of4patients; instage 2A 21 of26; stage 2B 5of12;
stage 2C 5of17patients, and instage 3nopatient had EEG
background activity within normal limits.
The PCs were usually bilateral, synchronous and sym-
metrical. PC amplitude asymmetry was seen in12patients
(Figure 1). Three patients had histories ofmeningitis while
they were approximately 6 months old, and in addition to
meningitis one was mentally retarded and another had hear-
ing loss. The remaining patients had nohistorical data to
explain the PC amplitude asymmetry. PC amplitude asym-
metry was intrahemispheric and also interhemispheric, and
was seen inevery stage, most frequently in2A. Lack ofPC
synchronization between the hemispheres was observed in2
patients (Figure 2). One patient had asynchronous PC althe
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202
these had ahistory ofmeningitis.
Six patients had more than one PC form. Ofthese 6
patients, 1 had meningitis and another had measles
encephalitis after he had had measles. Only 3patients had
prominent electrodecremental periods lasting from 1 to3
seconds following each PC. Continuous oralmost continuous
anterior delta activity after PC was seen in40patients mostly
instage 2A (Figure 3). Continuous delta activity was seen
predominantly over the anterior regions only during hyper-
ventilation inone EEG ofastage 2Apatient.
Focal epileptiform abnormalities were observed inmulti-
ple locations atevery stage in32 patients but most frequently
in frontal, central and temporal regions. Inonly 8 patients
were spikes detected at the beginning of the PCs. In25
patients, the epileptifonm abnormalities were separate from
the PC and they were also independent ofeach other. Spikes
were found both atthe beginning and apart from the PC inthe
EEGs of3patients. Generalized spike and waves seen in15
patients were noted primarily instages 2Aand 2B, mostpromi-
nent infrontal regions (Figure 4).
Inthe majority of patients a PC was noted with each
myoclonic jerk orhead drop. Inonly 1patient (stage 2A) dys-
tonic type involuntary movements without asynchronous PC
CLINICAL ELECTROENCEPHALOGRAPHY <C>2000 VOL. 31 NO 4

Fp2-FS"'(':"\ /""'\~
\.1
FS-T4 ···',:JJ,~V-V~
T4-16

16002

Fp1-F7

F7-13

13-15

T5-01

Figure 2.
Asynchronous PC (13y/M/stage 2B).

Fp2.F8

F8·T4

T4·16

Fp1·F7

F7·T3 ~---"'.­

T3.T5~
~~~ ~
T5-01 'f~J>;"'~" V:J .~~W' --...~~~(o/V'-
50JJV l - - . .
1 sec
Figure 3.
Anterior delta activity after PC and alpha like activity (14y/M/stage 2B).

were observed. No EEG findings were seen inthe patient
who presented with atypical SSPE clinically, and the diagnosis
was made with brain biopsy. In2patients ictal seizures were
recorded. In 1patient 2seizures were recorded; the beginning
ofthe first one was missed because it had already begun
before the start ofthe examination. The seizure consisted of
rhythmic slow sharp waves at5-5.5 Hz atthe right frontal-
centro-temporo-parietal and the left fronto-centro-parietal
regions, and appeared tobe generalized except for the pos-
terior regions. The second seizure occurred inthe form of
rhythmic activity at5-6 Hz, and was recorded over the left
fronto-centro-parietal regions and became generalized at
later stages, lasting for 21 seconds. Inthe other patient, 3
seizures were recorded during video-EEG monitoring. All 3
seizures were obscured bymuscle and movement artifacts
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203
but clinically the patient had pelvic thrusting and bipedal
automatisms, suggesting that his seizures most probably
originated from the frontal regions. The patient also had fre-
quent head drops synchronous with each PC discharge. IV
clonazepam was injected in14 patients during EEG exami-
nations but PC intervals and durations did not change follow-
ing the injection, however myoclonicjerks ceased. One patient
had PC over both hemispheres and periodic lateralized epilep-
tiform discharges (PLEDs) overthe right hemisphere (Figure
5). His clinical history was not distinct from the others.
DISCUSSION
Anew SSPE classification was applied to all patients.
The earlier classification described byJabbour etals was
not found tobe compatible with the clinical findings most of
the time. The classification should indicate that as the stages
CLINICAL ELECTROENCEPHALOGRAPHY C2000 VOL. 31 NO 4

Flgure4.
Atypical generalized spike and wave activity following PC (11 y/M/stage2A).

Fp2-F4~~~,.iV'i~" ""~- ~"-"""~~

v~

F4-C4 ~-./\.._~~~""'\ ...-I'lJl

P~2

Fp2-F8 ~_ _~ ~ '""""'"""""/V'

FI-T4

T4-T6

Fp1-F3 -v'""'-'"~~r'-' """--\

F3-C3 - '"'"-V,O""-'"-..r-'""- - .. ~\II

50J.lVL--
1 sec
FigureS.
Periodic complex with right-sided focal PLEDs (16y/M/stage 2A).

increase, the clinical findings become more severe but, as
mentioned above, the former classification did not quite com-
port with the clinical findings. The other existing classification
described byRisk and Haodad' was socomplicated that it
was difficult forthe clinicians touse; therefore, two different
doctors could sometimes stage apatient differently.
Our findings also support the statement that the back-
ground activity becomes abnormal and has low amplitude as
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204
the stages increase. 7 PC amplitude asymmetry was seen to
be more frequent inour patients than inother groups. Inour
series 12 patients had PC amplitude asymmetry, which was
either intra- orinterhemispheric. Itwas thought that asym-
metry of PC implied that one of the hemispheres was less
damaged. Except forthe 3patients with ahistory ofmeningi-
tis, neither specific history nor neurological findings could
explain the asymmetry. Inone study' apatient who has had
CLINICALELECTROENCEPHALOGRAPHY
right hemiplegia and aphasia since childhood was diagnosed
as having SSPE; the EEG showed PC only on the right hemi-
sphere. Asynchronous PC was seen in2ofour patients. The
asynchrony between the hemispheres iscompatible with
transcallosal propagation ofPC.9 The existence ofmore than
one type ofPC suggested that these discharges come from
more than one generator, orthat one generator developed dif-
ferent types ofPC.
Delta activity inthe anterior areas following PCs was one
ofthe most common EEG findings, followed byfocal epileptic
discharges. Anterior activity after PCs was seen in49.2% of
patients, so itshould be considered tobe one ofthe EEG cri-
teria for SSPE. Other studies 7•10,11 also mentioned the same
findings, as well as significant and frequent generalized spike
and wave activity and atypical forms ofgeneralized spike
and waves. 7,10Intwo reports 11,12this was noted as an unusual
finding, because while generalized spike and waves were
only seen during the waking period, PC appeared with the use
ofdiazepam.
Focal epileptiform discharges were other important EEG
findings. These abnormalities appeared as spikes orsharp
waves, especially inthe frontal, central and temporal regions.
These focal findings were sometimes seen prior to PC or
during the intervals between PCs. Inanother studyl3 itwas
mentioned that bioccipital spikes were followed byaPC. In
our study 8out of67 patients had spikes followed by a PC,
from different regions not only occipital. Electrodecremental
slowing was reported in3cases who had no historyofinfantile
spasms; their ages were 4,7and 16.
There was only 1seizure recording inaprevious study. 12
Inour 2patients the seizures, except for myoclonus orhead
drops, originated from different regions. Only 1patient out of
67 needed abrain biopsy because no specific EEG findings
(PCs) were found. The biopsy result was consistent with
SSPE. Existing EEG criteria ofSSPE were not sufficient to
describe all these EEG findings, therefore we concluded the
criteria had tobe improved. There were many reports claim-
ing atypical EEG findings ofSSPE inthe literature; however,
our series, the largest, displayed many examples ofsome of
these previously uncommon findings.
In astudy inwhich clinical, neurophysiological and neu-
ropathological findings were compared, itwas found that ill-
ness affected the occipital regions in early stages, and
involved anterior regions in later staqes." These findings
did notconform toours, since the most frequent observations
were delta activity over anterior parts ofthe hemispheres
and focal epileptiform discharges infrontal, central and tem-
poral regions especially inthe early stages ofthe disease.
Ithas been shown thatthe cortex had tobe intact orpar-
tially intactto generate PC. 141n later stages PCs are not seen
after cortical damage. This may also be true ofdelta activity in
anteriorhemispheres after PC.
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205
lCl2000 VOL. 31 NO 4
Further investigations are planned to analyze the
seizures comprehensively with video EEG monitoring. Sym-
metric and synchronous PCs are not always expected atthe
early stages ofSSPE, and also insome cases they are not
obvious atthe beginning. Delta activity inthe anterior hemi-
spheres after PC and focal epileptiform abnormalities are
the usual EEG findings. Most ofthe patients inour group
were instages 2A to2C and only 8ofthem were atstage 3.
The EEG findings inour study donot seem tobe specific to
SSPE. Atthe other stages where PCs occur and continue,
additional EEG findings can be observed.
While SSPE isnot seen in developed countries, dU3 to
the insufficiency ofmeasles vaccination this disease isstill
encountered ineither developing orunderdeveloped coun-
tries. Consequently the endeavors ofthe doctors who deal
with adisease that has such a bad prognosis and the rela-
tives ofthe patients as well as the patients themselves should
beappreciated.
SUMMARY
Inthis retrospective study 67 patients with SSPE seen
between the years 1980and 1998 were reviewed. Using the
criteria ofSSPE diagnosis (clinical signs, characteristic EEG
patterns, high titres ofmeasles antibodies inthe serum and
CSF), the patients were divided into two groups. Group A
fulfilled all criteria, however, due tothe inability ofmeasuring
measles antibodybefore 1987, itwas not possible toobserve
the third criterion inGroup B. Among 67 patients, groups A
and B consisted of 51 boys and 16girls ranging in age
between 1 to23 years, mean age 13.1. The male/female
ratio was 3.1.
The periodic EEG complexes (PCs) were usually bilater-
al, synchronous and symmetrical. PC amplitude asymmetry
was seen in12 patients and 2patients had no PC synchro-
nization between the hemispheres. Six patients had more
than one form ofPC. Delta activity inanterior hemispheres
after PC was seen in40 patients, mostly instage 2A. Thirty-
two patients had focal epileptiform abnormalities inmultiple
locations atevery stage but most frequently infrontal, central
and temporal regions. One patient had PC over both hemi-
spheres and periodic lateralized epileptiform discharges
(PLEDs) over the right hemisphere. The EEG findings
described and observed inour study donot seem tobe spe-
cific toSSPE but these findings were not atypical orunusual.
ACKNOWLEDGMENT
We thank Nurten Turan and Mustafa Ertas for their help
with statistical analysis and preparation ofthe figures and
Nazmi Asian, M. Ali «arik, Yavuz Nural, Emirzade Dagta~,
GUiver Karamehmetoglu for technical help.
This paper was supported by The Research Fund ofthe
University ofIstanbul.
CLINICAL ELECTROENCEPHALOGRAPHY
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