Central Nervous System Involvement in Systemic

Lupus Erythem atosas: A Review of Neur0pathologic

Findings in 57 Cases, 1955-1977
~ty Stephdn G. ~llis and M, A m h o n , Verity

ENTRAL NERVOUS SYSTEM '(CNS)

involvement in s~stemie lupus erythematosus iSLE) was first described by :K~posi in
1872.~ Tl~e clinical spectrurfi of CNS SLE was
clarified by Harvey'et ,al. ~ and Dubois and,coworkersa7~between 1949 and 1966, but a major
discussion of the pathology of CNS SLE was
first atLempted by Johnson ,and Richardson in
19.68)
The prognosis of patients with SLE has
improved in the last decade. This ~as beenattribuVed to the increased use of high-dose corticosteriods, hemodia|ysis, renal transptantation,~'-? and immua6s'uppressive drugs.:' These
advances in" therapy have altered the clinical
manifestations of SLE, most notably the causes
of death. D u ~ i s e t a l . ~ i n a serie,s of 249
patieff[s found that between 1950-1955 and
1963-1973 the percentage of deaths due to CNS
SLE decreased.' from 26% to 8%, those due in
renal death decreased from 26% to 14%, but
those due to infection (excluding tuberculosis)
increased .from 10% to t9%. Other recent large
series have noted a higher incidence of'death
from CNS SLE)" ~"~
Theparp~gse of this study is twofold: first, to
describe the spectrum of patho|ogy in CNS
SLE, and, second, to doctiment the changing
pattern of neuropatholo~ic disease daring the
last 20 yr.
Patients bearlng the diagnosis of SLE e c n f i r m ~ a t
autopsy at UCLA Center for :the Health Sciences bet,~een
I955 and 1977 were evaluated. Their eliniea~ charts were re~
viewed, and patients were rejected for.the purposes of this
study, if they failed'to meet the ARA criteria for the diagnosig of SLE erythemmosus as modified by Trlmhle et zl, ~
to allow substitution,of" a high-titer fluorescent antinttdeae

eat of Pt~thvlogy i~Veu

L
Ce~te~'for The Heal~hSienee.*, Los

~dd~ess fo~ rep~b~t re'qne:~ts: e~f. dnthotty Verity, M.D.,.

Profi,ssoe of Pathology, UCLA Comer for tfeulth 5"cieuee$.
Los Angeles. Ca/i~(90024
~ 1979.by,Grune &Stratton. Inc.
0049-0t72/79/0803~005502.00/0

21Z

Generat
The 57 patients had be~n a d m i t t ~ to UCLA Center for
the .Health Sciences From ~ to 14 times and foilo-~ced for
periods of 1 xvk to I I yr. "Neurolo~ Service consultations
were obtMned for 33 of the patients. ~ e r e were 47 females
and 10 radios: ages at time of onset of SLE ranged from I2
to 59 yr ,(6tean 31.3): and dt~ration of d~sease ranged from
onemo to l g y r (mean 5.7 yr).
The ARA ~creening liniea~ and laboratory findings for
these patients did not differ significantly from those
reported i~ other large series. :~-~-~'~-t~
P A T H O L O G Y tN SLE

The gross and microscopic lesions seen in the

CNS system in these 57 patients with SLE may
be divided conveniently into five major
pathologic patterns (summarized i~ Table i).
Vosc~ttopat.~y in C [qS S L E

MATERIALS AND METHODS

From the
UniverM~y of

antibodjy~r l~sitiv F LE cells. Th= patients" CNS tissue was

examined in detail; patients were ~ e | u d ~ from the study i f
ins~tfl]ei~t tissue was available. Additional sections were
obtained, and additio~a! staining methods (Kl~ver, Weil,
Bidscho~sky, and Holzer) were emlfloy~ when indicated,
Of the 80 ,patients originally diagnosed as 'having SLE, 57
were aeeepte~ into ~his study~
Thetincidence of microscopic findings was tabulated and
correlated ~'ith the clinical signs and symptoms, The mean
number of slidcs examined per ease did not direr in the two
~ime p~dods" examined (mean o f 8~1 slides/case for
1955-1965 a~d 8~3 ~'or 1966~ 1977),;The evaluation of tissue
sections and-~.eeauses or ~eath were performed without
knowledge of ;dett.*~f deaeh or t re~tm~mt. Statistical evaluat~ns were perf~i'raed asMg Student*s t test on means of
smat~ ~pulatior=~:

Previous studies showeMa variety 9 f lesions in

the small and large blood vessels of the CNS in
SLE):' True arteritis of cerebral vessels has
been a rare finding, but perivaseular infiltrates
of lymphocytes have been noted frequently.
True ~;asculitis with inflammatory cells within
the vessel wall was found in only 3 ~of 24 cases
examined hy Johnson and Richardson.~ In Table
2 we document the nature of vascular changes
found in our 57 cases and indicate their incid e n c e ' i n the periods under consideration.
Vascular hyalinizatign, especially of meningeat~
suhcortical,, and cortical arterioles, was common and occurred in over one-half the eases,

S~"nina~s~n A.,'tbrifts and'Ftheomatism. VOI. 8,. NO.~3 (Feheua~L 1979

CNS IN SYSTEMIC LUPUS ERYTHEMATOSUiS

213

with a significxnt incr, ease in the period

1966-1977. Perivascular 13,mphocytosis (Pig, :)
was found in 16 cases (28%). Endothelial proliferation (Fig. 2) was seen in t 2 cases (21%) and
has been ,described previously using the terms
intimat swelling and proiiferatlon,~;'-~ in two
cases evidence of an acute exudative capilla O,
vasculopathy ~(Fig. 3) was noted, characterized
by edematous degeneration'of the vasealar w~t,
perivascular hyaliz globule fo~ation, and surrounding spongio{ic edema. These changes are
analogous to those described by Johnson and
Richardson ~ (lheir case No. 9) in which loci o f
pericapillary ~agul~tion necrosis, often" with
ring hemorrhages, were identified. Tile capillary
vessels within these lesions showed thickening,
eo~in?philia, and refractilit~j of the walt resembling fibrinoid degeneration. Thrombosis
and/or evidence of vasculitis occurred in tess
than 15% of the cases (Fig. 4). No ~ a m p [ e of
la~e-vessel disease analogous to that seen in
polyarteritis nodosa was found in this series, al*
though one case showed meningeal large-vessel
thrombosis and organization (Fig. 5),
Although evidence of ischemie infarction wa\,~
noted in nearly one-hatf the cases (Table 3),
associated arterial and artedolar thrombosis
with organization was rarely identified. An organized, thrombosed araer~y was identified only
once (Fig. 6)and found in the wall of a cystic infarct in the striatum,

Table 1, lnc!Clan~a of Major Neuropathologtc Findings in 57

Autopsied Cases o! SLE

Vasc~foPathv

37 (65%)
25 (44%~
24142%)
16 (28%}

Infatctlon
Hemorrhage
(n~ection

Misc,|raucous
T~ansvetso myelopath
Pogress~vemult~f~-c~t

teukoencepfial~pathy
Hodgkin diseas~

Infarction in CA~5;S L E
As shown in Table 3, the incidence of large
and small multifocal infarctions within the
central nervous system was 30% and 53% in the
1955-1965~and 1966-1977, respeetiv~y. Both
micmlnfarcts and larger infarcts (measuring
more than I cm ~n dimension) increased in inc)denee (p = O:OI). Most microlnfarets (Figs.
7, 8) were ~n the superficial convexity of the
~ r t e x (miliary e~rtica! infaretL and their apparehl increase in incidence du~'ing the latter
period may be a reflection of a more critical
awareness of such pathology and, its identificat)on on gross eam~natmn or a manifestation of
increased microvaseular hypersen~h,;vity due to
changing therapeut~e moda[hies. ~vlicroinfarcts
were seen most commonly in the parietal and
temporal pole convexities, within the pons (Figs.
9, 10) and occasionally elsewhere in the brain

Table 2. Incidence art~ Manifeslations of VascuIar Lee;one in CN S SLE

Vascular hyalinixalion
Pefivascular ~nflamr~tion
(without obvious infcc~io.~]
Endothefial proliferation
Thrombosis
Vasc~lit~S(w~thout irt{ection|
~otal I~ases)

1955-~ 965
~23Ca$~)

1966-.1976
i34 Cases)

Total
(57 Cases)

5 (22%}

:16 (76%)

31 (54%)

6 (2:6%)
3 (13%)
I (4%)
2 (9%)

10 (29%)
9 (26%)
3 (9%)
2 (6%1

16 (28%}
12 (21%)
4 (7%}
4 {7%)

14 (5t%1

26 (76%}

37 (65%}

0,01

Tat=le 3. il~dder~ce d |nf;~rcts in CN$ SLE

Mic~oinfacl~
Large infarcts
Total (cases)

~955-T 965
(23 C~sesY

t966~tg76
(3 Cases)

t57 Ca~es)

6 {26%)
2 (9%)

14 (4t%)
S (I 5%}

20 (35%)
7 (12%~

7 {30%)

18 (53%)

25 (44%)

0.01

2 ~4

ELCIS AND VERITY

Fig. 1. Cortica| ~-erlatte~ot~ tymphocytos~s ~-~ 20~yr-old left, ate ~;th 1-y histo~-y of SUE ar~ ~ephfot~ syrct~ome.
H~E~ ~ 35.
F~. 2. En~t.~|ia| pro|~arat~o~ w/th 8ng~omato~ featut'e~ ~n deep su|cat coct~ of fr~ntat h a m ~ h e r e in 51-t-o|d femate
hospita|i2ed frJf g~)stroir)test~na! b~esd~ng and |eft oocip~ta|
hemorrhage. HistoW of SLE. P~ph~t~is.and hypertensior).
H&]E. >~ 60.
Fig. 3~ Acute caPii|ary endothelie| ewe|ling, exudz~ive vascuiopathy, psf~capi|lary hya][~ glot~t~ deposition, and pa~nchyma|
spo~giosis. H&E. 60.
Fig. 4. Necrot~ing vasculitis with thrombus format~n in 36-yr-oid female with SLE. hyr~-.ertenston,afiemia, and termlnai
sLtbaCu~ebee|aliBi e~ocarditis. Miliary mlcroabsc;esses ware four~ in heart a ~ rungs H&E. 60.
Fig. 5. Organizit~g reca~alize4 meningea| artery over temporal p01e iR 34~yr.old female with 7.yi. history of SLE. tupus 91o.
me~u|o,ephritis, arid c|~=icai|y dorumonted CNS vasculitis 3 yr prior to death. Elastic-van Gieson~ x 10.
Fig. 6. Thrornbosed. o~iteratad artery in walt of linear cystic ;nfar~ of external c~s~|e. H& E. 12.

CNS IN SYSTEMIC LUPUS ERYTHEMATOSUS

215

Fig. 7. J~+mutecortical necrosis involving depth of sulcus in 64-t-o~d female w i t h 6-y history of SEE treated wPlh daily
predelsone, Teirminal course complicated by metastatic adenocarcinoma of lung. Wail stalo~ ~< 6,
Fig, 8. Chronic subcortical mtcroseople infarcts in sem~t patient aS Fig, 7, Wail stain. X 5.
Fig, 9, Ttansvexse sectioo of pone shgwing t w o cystic infarcts in baslspDntis in 22.yr-old black male w i t h 5-yr history o| SLE,
lupus nephritis, ceeehr|tis, and restrictive lung all)sense. Hyperplastie and filcrinold uascttlopathy was found in pancreas, liver, peripheral nerves, end adrenals. Weft strain, x 4.
Fig. 10. MicrOscopic detail of same patient~as F;g. 9 showing subacute damyetination, meGropheges, end gliosis at border of
microlmfatct+ H~E, x 35.

stem or pallidus. Microinfarets were not found

in the cerebellum. The sites or larger infarcts
were more varied, but l h e s e infarcts..,/vere
usually found in the distribution of t h e mid<lie
cerebral artery.

Llemorrh.ge tn CArS SLE

Twenty-four cases (42%) showed prominent
hemorrhage (Table 4). Evidence o f acute or

chronic h e m o r r h a g e into the subarachnoid

space was present in 17 (30%) of the cases. In
all cases except l, this was accompanied by intracerebra[ hemorrhage (Fig. l l ) or diffuse
petcchial microhemorrhages (Figs. 12, 13),
especially throughout the subcortical white
matter. Subdural hemorrhage (Fig, 14) was
uncommon, occurring in only 2 cases. !n' the 7
cases o f d e m o n s t r a b l e vascuIitis (wit~ and

Teb|e 4. IncSdenCe of H e m ~ h s g e in CN S SLE

Su~rachnoid hemorThage"
M~ohemorrhages
~mrace, ebfal hemorrhage
$U~JU~a! P ~ o r r h a g e
Total (cases)
j

- -

=,

t955-~965
|23 Cases)

I966~1976
(34 Cases)

Tofal
157 Cases)

6 {26%)
5 (22%3
2 (9%)
~

11 {32%)
6 (I 8%~
4 (112~
2 (6~

| 7 ~30%J
11 (t9%)
6 (t 0%)
2 {4~

110(43%)

114(4 | %)

24 (42%)

* Included ate eases showing p r o m i n ~ l menlngea$ hemosiderin dap~it=ons.

~,

2 16

EI~)S=AND VERITY.

Fig. 11, H e r o , s o m a in patttcenlra) Iotmla el posterior hami~phele ~m'to'anded by Pe|at~hit~l h@motthagas corstaining Candida
sp. in 23-yr-oid lem~le v,~th ?.~r SLE. bdatatal glomerulot~tephtitis, bone marrow hypoolasia, a~d~pane/top~?ia. Other small
hemorrhages are noted in the splenium end 5uperio) parietal Iohule. T0rrninal ;ourse c0mplicated by pnaumon,ia, C a . ~ i a a sepsis.
and CNS involvement,
Fig, 12. Peteehial hemorrhage in ~ttll~orticat wh)te metier with c e n t r ~ "~tart~rst'" effect. H&E. 30.
Fig+ 13. Diffuse spreadingperivenular,hemorrhatlawith transmural taft|trOt+Ors e l inflammatory cells+ H~E+ x 25.
Fig, 14, Resolving sut3dural hemo.haga, H~E. I 0 .

without infection), the incidence of subarachaoid hemorrhage was high (71%) compared to
the incidence of subarachnoid hemorrhage in
tire absence or vascutitis (24%),

lnJi'ction i, C N S SL E
The incidence of CNS infection confirmed at
necropsy increased from 17% to 35% between
1955--1965 and 1966-.1977 (p = O.OY). As
~malyzed in Table 5. this is reflected in the incidence of meningitis, which has increased sixfold.
Aseptic meningitis is a rarely document~ feature o f C N S SLE but may precede and herald a
diagnosis of SLE. ):'- v, Johnson and Richardson ~
Ibund eight instances of |upus cerebritis with

pleocytosis" hut no evidence of bacterial infection. Keeffe et al, ~3 described a case of lupus
meningitis and indicated that, lupus cerebritis
should be included in the differential diagnosis
of meningitis when infectious causes have been
excluded. The dramatic increase in meningitis
seen in our series was not due to an increase in
a s e p i i e " ~ n i n g i t i s (Fig. 15) but' correlated
closely with the increased incidence of bacterial
(~ig. 16) and mycotic infections (Figs. |%=20):
TaMe 6 summarizes the infecting organisms
i,~3Iated from the C N S in patients presenting at
autopsy with meningitis. In n o case were septic
emt~Mi demonstrated within cerebral vessels as
in the case of lupus adocarditis r e ~ r t e d by At-

217

CNS IN SYSTEMIC LUPUS ER~HEMATOSUS

Table 5. Manifestation of CNS Infection in CNS SLE
~955- ~965
(23 Ca~s~
Meningitis
Pettvascu|ar inflammation
with infection
Septic hemorrhages
Vasculit=s with infection
Focal cerebfitis
Tota| (cases}

! 966~~976
(34 Coses)

~'ota|
(57 C;~$es)

2 (9%)

9 (26%)

~0 (I 8%)

0~0

2 (9%)
I (4 %,*
1 (4%)
0 (~)

6 (! 7%)
2 (6%)
2 (6%;
2 (6%)

8 (~4%)
3 (5%)
3 ~5%)
2 (3%)

----

12 (35%)

16 (28%)

0.03

~4~(~7%}

bertini and Alb. ~" In our series no.consistent

relationship was found between cerebral lesions
and endocarditis, in agreement with observations of Johnson and Richardson? ~

Clmicopathologic Correlation in C N S S L E
....Two out of every three patients with SLE
showed clinical evidence of C N S involvement.
Seizures were most common (24%), followed by

severe or persistent headache (23%), hemiparesis (21%), crania| nerve palsy (19%), and psychosis (14%). Multiple" ncurologic s~,mptoms
were seen in two-thirds of those with clinical
findings. Crafiial nerve palsies were most often
as~gcjated with other" findings (81%) and were
o f t e n m u l t i p l e ~, as had been p r e v i o u s l y
reportcd. ~ "~:~In comparing the cases coming to
autopsy from 1955-1965.. with those from

Fig. 15. Deep ~lcal~ eccentr~ ~ r ~ o n u l s r focus of |ymphoc~es consistent with isep1~ meni,gitis~ H& E. 15.
Fig~ 16. Embo;~ abscess in.molecu;at layer of c e r e ~ l | a r foltum with surrounding spongtos|s and g|tosts ir~ 21.yr.o;d female
with I~pus n ~ h r i t i s , chronic gtomeru|itis, u m m i l , s ~ S. aureus h~te~emia~ H & [ . x 25~
Fig, I 7 . N ~ o t l z t n g granu|omat~s mycotic abscess in ceret~tl|at dentate nucteus in e 27*yr-o|d female with lupus nephtltis
end ~ y l 4 ~ r o ~ S receding |ong-tefm Wednlsone I n d ~othiopt|ne thet~y~ R a t e g t l n t e||s are visua|ize(| 8t peripheW of
absces~ E~ colil~tpticemil andpfetermtna| CandidlaslS, H&E. x 10.
Fig~18. D e t s , cd same cese as Fig~ l T showing hyphsl focms of Cer~dlda ttoptcsdis in abscass. H& E. x 65.

218

ELLIS AND VERITY'

~n~r~ht hemisphere and ce~ebellu~m. P e t i o ~ ~cid~S~hiff, 12.

Fig. 20, Same ~ s e as Fi 9. $9. showing Cryptococc~ n ~ o / / n a a a utganisms it; s u ~ t a c h n o i d space a~d s u r r o u n d i ~
nlngeat vessels, Pe~iod~ a;d-Schiff. >~ 6~.

1966-3977, no significant change in the clinical

presentations was noted. ~
A comparison of the major clinical features of
CNS SLE with the common pathologic findings
is given in Table 7. This-comparison indicates
the incidence o f s i x pathologic findings in 12
patients with hemiparesis, t I patients wit:,~weltdocumented seizure history, and 11 patients
with eraniat nerve dysfunction. Demonstrable
microinfarets, intracerebrat h e m o r r h a g e ,
ahd/or subarachnoid hemorrh~.ge occurred ~n
one-half the patients with hemiparesis, P,'~tients
with a seizure history had a high incidenceof microinfarcts and subarachnoid hemorrhage. The
subarnchnoid h e m o r r h a g e round in these
patients was often accompanied by meningeal
hemosiderosis, indicative of'prior bleeding.
Noteworthy was the absenceof large infarcts in
patients with prominent seizures, Microinfar~.ts
were identified in "nearly three-quarters of
patients with cranial nerve palsies and are presumably often the etiologic basis for this finding.
Table 6. Organisms Isolated i~ Cases of CNS SLE
Associated With Autopsy E~dene of Men~l~lifis
~

~955-1965

1966-1976

"'AsepT~"

S. aul,eu~

Candlda sp.

CtVptocorcus
A:;pet g#t,ss
7oxr~plaSrno

2
I

Strep10~ecus sp.
Total cases

r~.~-

While the focal motor seizures were often

associated with evidence of chronic subarachnoid hemorrhage, the more common grand real
types of seizures were associated with a high incidence of cortical infarction: Grand real
seizures have previously, been retorted more
commonly ifi Patients with CNS SLE than those
of the focal motor type: '~'-~DISCUSSION

Comparison of frequencies of microscopic lesions in CNS SLE in various series is somewhat

fallacious because Ol"the local nature of many of
the lesiong:and the differing methods of study,
The number of even.moderatelysized studies in
the literature examining the neuropathology of
SLE is small. The classical study of Johnson
and Richardson,f' with 24 cases, is the most
comprehensive. Other reportsjnclude the series
of Matamud and Saver, ~L Feinglass et ai.. e~
Gibson and Myers, ~'~ and Walravens and
Chase, ~ and numerous detaile~t single case
re~rts. Our data are similar to those in other
series, with three principal exceptions: (1)The
incidence of meningitis and evidence of in rection
is greater in our series-than that found in previous studies; our data comparing cases from
1955-1965 with those from 3966-1977 support
the finding that the incidence of CNS infection
in SLE patients.is increasing. (2)The incidence
of subarachnoid h e m o r r h a g e is s o m e w h a t
greater in our series than in othez:s. (3) The incidence of microinfarcts (35%) is tess than that
reported by 3ohn~n and Richardson~{70%) but

CNS IN SYSTEMIC LUPUS ERYTHEMATOSUS

.o T a b i e T .

219

Maj~rN~u~pa~h~g~Fir~d~sinCNS~LEPatients~ithHemipa~esis*~eizu~es~andC~aniaINe~Pa|sies

Hem~pacesis (~ 2)
S~Jures (I ~)
Cranial nePve
pa~sies (1 I )
To~a! cases (57)

Mt~o ~
~|arl$

Lage
Infarcts

63

33
0

50
27

72

35

12

similar to that given by others. In most studies

the distinction between arteritis, with .inflammatory calls invading walls of the vessels, and
pefivascdar inflammation is not c i n d y made.
Nonetheless, the combined incidences of these
lesions in the various series are similar.
The underlying pathogenesis of the CNS
manifestation is unclear, ~t although there is
agreement that the major lesion is
microvascular injury. It has been suggested that
the deposition of soluble antigen-antibody complexes in the choroid plexus plays a major role
in the pathogen~is of the nervous and mental
manifestations of SLE2 ;~3 Of our 57 patients,
3 showed inflammation and/or endothelial proliferation in the vessels of the choroid plexus,
but I~ht-microscopic examination has not been
reported as rewarding. Proponents of this
theory point to the study of Johnson and
Richardson,~'who found vasculitis in only 3 of 24
cases. Reexamination of their data, however,
shows CNS vasculitis in 3 of 6 patients dying
from neurologic causes. Our data similarly
show an increased incidence of vasculitis in
patients autopsied with active CNS disease defined by the presence of progressive clinical j~eurologie signs during the final hospital admission.
Additionally, vasculitis appears pathogenic in
many CNS hemorrhages ffable 8), especially
subarachnoid hemorrhage. Feinglass et al. ~
found that in 84% of patients who developed
neurologie signs or symptoms, complete or
T a b l e 8, In--dance of Hemo~h~ges in Documented C N S
SLE Vascu||tls

Subarachnoid

;ntracerebral
Microhemoffhage
Total

V~sc;ubt~s*
~7C a ~ )

No Vascu|~Its
(50 ~ses)

5 (7 | %)
3 (43%)
3 (43%)

~2 (24%)
3 (~
8 (~ 6%)

6 (86%)

18 (36%)

"The seven cas~ of vascul~tis include those with a ~ without

evidence of infection

cerebca|
Hemor~hag~

Men~n~
Oi~s

Vascghl~s

50
54

25
18

25
27

18

10

30

18

13

Sg~aachno*d
Hemo~hage

partial recovery was the rule. These data, and

the fact that CNS SLE vasculitis is focal and
may be short-lived, suggest that the incidence is
greater than previously thought and may be
pathogenic in many of the clinical manifestations of CNS SLE. Cutaneous or visceral
vaseulitis has been reported in 46% of patients
with clinical signs of neurologic involvement,
whereas it has been seen in only 17% of those
without, z~ Lee et al: ~ agreed that vasculitis is
responsible for some but not all clinical
manifestations, even in the absence of uremia.
Numerous reports document the variety and
frequency of the clinical manifestations of CNS
SLE. The neurologic signs and symptoms are~
similar, but their reported frequencies vary. ~ ' "
Lee et al. ~ s h o w ~ that patients with CNS
manifestation had more severe disease, especially in the incidence of nephritis, than those
with no CNS involvement.Table 9 contrasts the
incidence of neurologic manifestations in our
series with that of Johnson and Richardsone'and
a predominantly nonautopsi~_t series derived
from the literature. In most respects the incidence of clinical manifestations in our series is
similar to that in the literature, except for the
higher incidence of hemiparesis, perhaps because our patients were followed to the end of
Table 9. Incidence of Neuropsychtatric
Man~festatlons in SLE

Se;zures
Headache
Hero,paresis
Psychosis
Crania! n e ~ e
patsy
Cerebellsr
signs

Th~s

John~n
and

(57 Ca~s)

{24 Cases)

24
23
21
14

~
~
13
33

22 (7-57)
18 (8~31 )
9 (0-113)
38112-59)

19

42

15 (5-42)

13

5 (5-16)

I.~te~at~e

Inciden~s are expressed as p0rcentages, The hteratufe series

is compiled from Flels~2 - 4 . 12~ 17, 23, 24, 26, and 37~42~

220

ELLIS AND VERI~

their clinical course, as contrasted with many

other series. Similarly, our overall incidence of
neurologic clinical manifestations (67%) is
greater than that generally r e t r i e d (1,9%75%). Our data suggest that neither the incidence nor the variety of clinical manifestations
of CNS SLE is changing, with the possible exception that seizures may be declining in frequency (not statistically significant), which is
paradoxical in view of the changing
micropathology.
Our data support those of Dubois and coworkers~'~ in clearly showing that frequencies in
the causes of death in patients with SLE are
changing. Death by severe infection, often with
organisms previously considered rare (LL~teria,

Toxoplasma, and variouslfungi), is becoming

common as patients ai:e ~treated wRh toxic
drugs. The infection rate of patients with SLE
treated with corticosteroids is greater than that
of patients with the nephrotic syndrome similarly treated+ a~ Defective phagocytosis, 32
decreased leukocyte chemotaxis,~3 lymphocytotoxic serum factors,:" a n t i . d i e s to circulating granuloeytes, ~ and impaired delayed
hypersensitivityaG have been reported in SLE
and surely contribute to the increased susceptibility for opportunistic infection. Increased infection rates are also seen in SLE patients
t r e a t e d with more than 50 m g / d a y of
prednisone as compared to those not receiving
corticosteroids.:"

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