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Cerebral toxoplasmosis complicating the acquired immune deficiency syndrome Clinical and neuropathological findings in 27 patients.

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Cerebral Toxoplasmosis Complicating the
Acquired Immune Deficiency Syndrome:
Clinical and Neuropathologcal Findings
in 27 Patients
Bradford A. Navia, MD," Carol K. Petito, MD,? Jonathan W. M. Gold, MD,$ Eun-Sook Cho, MD,§
Barry D. Jordan, MD," and Richard W. Price, MD"
We reviewed the clinical, neuroradiological, and serological findings in 27 patients with cerebral toxoplasmosis complicating the acquired immune deficiency syndrome, 19 of whom were also analyzed neuropathologically. The clinical
manifestations of this disorder varied, ranging from headache and fever to coma. However, the characteristic presentation included focal neurological symptoms and signs, usually of subacute onset. In addition, two-thirds of the patients
exhibited more generalized cerebral dysfunction with confusion and lethargy. The computed tomographic (CT) scan
most commonly revealed ring contrast enhancement, which appeared to correlate best with the histological presence
of vascular proliferation and inflammation surrounding the abscesses. However, in 5 patients the CT scan revealed
either homogeneous enhancement or no enhancement, and in 3 patients the scans were negative. In general, CT scans
underrepresented the number of lesions eventually documented pathologically. Double-dose contrast administration
and preliminary experience with magnetic resonance imaging suggested that these techniques were superior to
standard CT scanning in detecting Toxoplasm lesions. All patients were seropositive for IgG antibody against Toxoplasma gondii in blood, both before the onset of illness and at the time of presentation, although titers in some patients
were as low as 1:8 and most patients did not exhibit rising titers. Prompt therapy resulted in rapid clinical improvement, documented by CT scan, associated with the development of an organizing tissue response in the host and
elimination of free organisms. Response to treatment was sufficiently rapid in most patients to allow a trial of therapy
as the favored approach to diagnosis.
Navia BA, Petito CK, Gold JWM, Cho E-S, Jordan BD, Price RW: Cerebral toxoplasmosis complicating
the acquired immune deficiency syndrome: clinical and neuropathological findings in 27 patients.
Ann Neurol 19:224-238, 1986
Cerebral toxoplasmosis was, until recently, a relatively
rare disorder in adults that occurred principally in the
setting of lymphoreticular malignancies, organ transplantation, and other disorders that are accompanied
by impaired cell-mediated immunity E6, 21, 2 4 , 4 5 , 4 6 ,
52, 541. The diagnosis of cerebral toxoplasmosis was
often missed because of its infrequency, because of
failure to recognize its various clinical presentations,
and because of the limitations of neurodiagnostic studies before the introduction of the computed tomographic (CT) scan. With the advent of the acquired
immune deficiency syndrome (AIDS), the frequency
of toxoplasmosis has increased such that in many institutions like our own, which are located within geographical centers of the AIDS epidemic, it is a com-
mon cause of brain abscess 11, 2, 5 , 8 , 23, 25, 28, 31-
From the Departments of 'Neurology, TPathology, and $Medicine,
Memorial Sloan-Kettering Cancer Center and Corneli University
Medical College, New York, N Y 10021; and the IiDepartment of
Pathology, University of Medicine and Dentistry of New Jersey,
New Jersey Medical School, Newark, NJ 07103.
Address reprint requests to Dr Price, Department of Neurology,
Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New
York, N Y 10021.
33, 42, 50, 5 5 , 577.
In order to clarify the clinical profile and diagnostic
approach to this disorder, we reviewed our experience
with 27 patients with AIDS who developed cerebral
toxoplasmosis, 19 of whom were, also examined
neuropathologically. This experience allowed us to
correlate the clinical features, neuroradiological and
serological findings, and response to therapy with the
neuropathological changes. Such correlation permits a
clearer view of the natural history of the disorder and
provides the foundation for an approach to managing
these patients that emphasizes the importance of
neurological signs, C T or magnetic resonance imaging
(MRI) scan, blood serology, and therapeutic trials.
Received June 14, 1985, and in revised form Aug 9. Accepted for
publication Aug 14, 1985.
Material and Methods
Between September 1980 and February 1985, central nervous system toxoplasmosis was diagnosed in 27 patients with
AIDS at Memorial and New York Hospitals. Direct histological confirmation of toxoplasmosis was available in 19 patients: 16 at postmortem examination and 3 by cerebral
biopsy (2 of the autopsied patients also had a positive
biopsy). In the remaining 8 patients, diagnosis of toxoplasmosis was made on the basis of clinical presentation, CT scan
findings, Toxoplasma serology, and response to therapy.
IgG antibody responses to Toxoplasma gondii were determined either by indirect immunofluorescent antibody (IFA)
1441 (15 patients) or by the Sabin-Feldman dye test [l6] (10
patients). Serum IgM concentrations, as determined by IFA
and complement-fixing antibody titers, as well as IgG responses in the cerebrospinal fluid (CSF), were also evaluated
in a number of patients. When more than one sample was
available from an individual patient, paired serum samples
were assayed simultaneously.
After fixation in 10% buffered formalin for 2 to 4 weeks,
the brain and spinal cord were serially sectioned into 0.5-cm
to 1.0-cm slices. Multiple sections from each patient were
embedded in paraffin and stained with hematoxylin-eosin
(H&E)and, when indicated, with Giemsa, Lux01 fast blueH&E, and Bodian stains. Immunohistochemical studies to
detect parasite antigens were also carried out using a convalescent human serum against T . gondii in conjunction with
the avidin-biotin immunoperoxidase method [7, 261.
All patients were male, ranging in age from 28 to 59 years
(mean, 38.6 years).Twenty-five were homosexual (3 of these
were also parenteral drug abusers), one was a transfusion
recipient, and one denied any risk factors but was suspected
to be homosexual. Central nervous system toxoplasmosis
was the initial manifestation of overt AIDS in 6 patients; in
20 patients it developed 3 weeks to 18 months (mean, 6.8
months) after the diagnosis of AIDS. In 1 patient the diagnosis of AIDS was determined only at postmortem examination. Of the patients with antecedent manifestations of
AIDS, 12 had Kaposi's sarcoma, including 9 who also suffered from opportunistic infections; 7 had opportunistic infections alone; and 1 had lymphoma and cryptosporidiosis.
The spectrum of systemic opportunistic infections was similar to that previously reported in AIDS patients 1151.
Clinical Presentation
Table 1 summarizes the clinical presentation, results of
CT scans, treatment response, and neuropathological
findings in the 27 patients. Central nervous system
toxoplasmosis was clinically suspected in 22 patients,
and diagnosed at postmortem examination in the remaining 5. However, retrospective review of the clinical records of these 5 patients revealed symptoms or
signs referable to the brain infection. The onset of
neurological symptoms and signs prompted admission
in 17 patiehts and developed in 10 others while they
were hospitalized for other medical reasons. The tem-
poral profile of the disease was usually subacute, with
symptoms evolving over 1 to 2 weeks, although 8 patients when first seen exhibited either an acute confusional state or focal neurological deficit accompanied
by headache.
Table 2 lists the neurological symptoms and signs in
the patients. Twenty-four showed focal abnormalities
when first seen, most frequently manifesting as a mild
hemiparesis. Signs of either brainstem or cerebellar
involvement were detected in 8 patients but were the
chief presentation in only 3. These included ataxia in
6, limb dysmetria in 2, and cranial nerve palsies in 2.
Seizures developed in 4 patients and were focal in 3.
Clinical signs of basal ganglion dysfunction were infrequent, but 1 patient had choreiform movements of the
distal upper and lower extremities and diffuse rigidity
and a second had left-sided choreoathetosis. Of the 3
patients with no focal deficits, 2 were first seen with an
altered mental status and 1 had headache only.
A diffuse encephalopathy, most commonly characterized by confusion and lethargy, was present in 17
patients. Of the 15 patients who exhibited both focal
signs and diffuse encephalopathy, the latter dominated
the clinical presentation in 11. Disturbances in arousal
were mild at onset but progressed steadily to stupor or
coma over 1 to 2 weeks in 8 patients. Two other patients presented with antecedent behavioral disturbances, one with paranoid psychosis and the other with
increasing anxiety and agitation. Delirium developed
in 2 patients, with progressive confusion in both and
visual hallucinations in one. In 6 patients the mental
status fluctuated without clear explanation.
Headache was a major complaint in 15 patients,
either developing at the same time as other neurological manifestations or, less frequently, preceding them
by 1 to 4 weeks. The headache was characteristically
bilateral, severe, and persistent, frequently awakening
the patient at night and responding poorly to analgesics. In only 2 patients was it predominantly unilateral.
Meningeal signs were absent even in those patients
with a CSF pleocytosis. Persistent fever accompanied
neurological symptoms in 15 patients. Toxoplasmosis
chorioretinitis was documented by culture in 1 patient
4 months before the onset of neurological symptoms.
In 7 others, retinopathy characterized by cotton-wool
exudates with or without flame-shaped hemorrhages
was noted, but the cause was not established.
Global cognitive impairment in the absence of decreased arousal, indistinguishable from that of the
AIDS dementia syndrome commonly found in patients without toxoplasmosis (Navia, Jordan, Price: unpublished observations, 1985), was noted in 18 patients at some point in their clinical course. Its salient
features were impaired recent memory, attention
deficit, and slowness of verbal and motor responses.
These fihdings preceded toxoplasmosis in 9 patients,
Navia et al: CNS Toxoplasmosis 225
Table 1 . Summary of 27 Patients with AIDS with Cerebral Toxoplasmosis
Duration of
CT scan
Toxophrm-Related CNS Pathology at Autopsy'
Onset of
Symptoms Tissue
to Death
Tachyzoites Cysts Location
I da (?)
Lethargy, confusion
Not done
1 da
I wk
Lethargy, confusion,
aphasia, coma
Single hypodense
lesion (no contrast): L frontal
Pyr/sulfa, 1
N o response, died
8 da
2 wk
Confusion, aphasia,
lethargy, seizures
2 wk
3 wk
Headaches, lethargy,
Single hypodense
lesion (no contrast): L frontal
Cortical atrophy
(no focal lesions)
3 wk
3 wk
Confusion, psychomotor retardation,
Cortical atrophy
(no focal lesions)
3 wk
3 wk
Confusion, lethargy,
delirium leading
to focal seizures,
Multiple hypodense lesions
Pyrisulfa, 3
N o response, died
4 wk
4 wk
Chorea, rigidity,
confusion, lethargy leading to
Hypodense lesions: bilateral
basal ganglia
Pydsulfa, 2
N o response, died
4 wk
2 mo
Focal seizure, confusion. lethargy, delirium, coma
2 mo
5 wk
Headache, hemiparesis, choreoathetosis
(1) Negative, (2)
Single hypodense lesion (no
contrast): R occipital
2 ring-enhancing
lesions: R occipital, L internal capsule
N o response
9 wk
necrotizing (peripheral)
12 da
13 da
2 wk
Pydsulfa, 4
2 wk
1 wk
1 wk
2 wk
1 wk
Lethargy, Confusion
leading to stupor
Headache, R parietal syndrome,
Headache, cranial
nerve palsies,
Hypodense lesions: bilateral
basal ganglia
Single ring-enhancing lesion:
R parietal
Pyr/sulfa or
clinda, 7
Initial improvement, died of
Candidu sepsis
Initial improvement, status
epilepticus, died
6 wk
9 wk
Single ring-enhancing lesion:
R occipital
>6 mo
Improved, died of
unrelated causes
6 mo
Headache, lethargy,
confusion, hemiparesis leading to
Single ring-enhancing lesion:
R frontal
10 mo
Improved, died of
unrelated causes
10 mo
Headache, ataxia, Lsided dysmetria,
VI-nerve palsy
2 homogeneous
enhancing lesions: L parietal,
>6 mo
Improved, neurologically stable
>6 mo
Headache, lethargy, confusion,
aphasia, stupor, L
central VII-nerve
palsy, ataxia
Multiple ring-enhancing lesions:
L frontal
3.5 mo
Improved, died of
unrelated causes
4 mo
226 Annals of Neurology
Vol 19 No 3 March 1986
Organizing, 0
Multiple lesions:
cerebral cortex
Multiple lesions:
cerebral cortex,
centrum semiovale, cerebellum
Single large lesion:
cerebral cortex
Multiple small
(0.3- 0.5 cm)
lesions: cerebral
cortex, cerebellum
Multiple lesions
(2-4 cm): cerebral cortex,
basal gangha,
Multiple lesions:
cerebral cortex, centrum
semiovale, basal
ganglia, cerebellum, brainstem
Multiple small lesions: cerebral
cortex, centrum
semiovale, basal
ganglia, thalamus, and cerebellum
Multiple lesions:
cerebral cortex,
basal ganglia,
and cerebellum
Multiple lesions:
cerebral cortex,
basal gangha,
thalamus, cerebellum, and
spinal cord
Multiple lesions:
cerebral cortex
and basal ganglia
Few lesions: cerebral cortex and
centrum semiovale
Multiple lesions:
cerebral cortex,
cerebellum, and
Multiple (2-4
mm) lesions: cerebral cortex,
basal ganglia,
Multiple (0.5- 1.5
cm) lesions: cerebral cortex,
basal ganglia,
thalamus, cerebellum
Multiple lesions:
cerebral cortex,
basal ganglia
Table 1. (Continued)
Durauon of
3 wk
Headache, hemiparesis, focal seizure
Multiple bilateral
clinda, 11
2 wk
Lethargy, confusion,
Pyrlsulfa, 5
10 da
Confusion, aphasia,
10 wk
9 da
1 da
4 wk
2 wk
Confusion, psychomotor retardation, aphasia,
Headache, aphasia,
memory loss,
Headache, ataxia,
sensory symptoms
Single ring-enhancing lesion:
R basal ganglion
Single ring-enhancing lesion: R
2 dense-enhancing
lesions: R occipital, cerebellum
Multiple ring-enhancing lesions:
L hemisphere,
basal ganglia
2 ring-enhancing
lesions: L frontal
Improved, relapse,
remission; died
of unrelated
Improved, died of
unrelated causes
Single ring-enhancing lesion:
L parietal
2 wk
2 wk
3 wk
Headache, L leg
3 da
4 da
Headache, psychomotor retardation,
lethargy, confusion, L central
VII-nerve palsy,
L homonymous
at m a
Psychomotor rerardation, confusion,
lethargy leading
to stupor, R central V11-nerve
palsy, a tm a
C T Scan
Headache, L central
VII-nerve palsy, L
inferior quadrantanopsia
Headache, transient
Toxoplusm-Related CNS Pathology at Autopsy"
Onset of
Symptoms Tissue
to Death
Tachyzoites Cysts Location
12 mo
7 wk
Improved, died of
11 wk
. ..
clinda, 11
6 mo
Improved, died of
unrelated causes
11 mo
., .
Improved, died of
unrelated causes
6 mo
. ..
14 wk
Improved, died of
unrelated causes
18 wk
dose), 9
Pydsulfa, 3
Improved, relapse,
recovery; died
of unrelated
Improved, relapse;
died of unrelated causes
9 mo
3.5 mo
lesions: R hemi>2 mo
(1) cortical atrophy Pydclinda,
>7 mo
(2) (3 weeks
later) 3 ring-enhancing lesions:
L frontal
Multiple homoge- Pyrlsulfa,
>4 mo
neous enhancing
lesions (double
Improved, relapse,
lost to follow-up
Single ring-enhancing lesion: R occipita!
3 ring-enhancing
lesions: posterior, temporal
3 ring-enhancing
>4 mo
Few small (0.2 cm)
lesions: cerebral
t . .
'Postmortem examinations were not performed in Patients 17 through 23; Patients 24 through 27 ace still alive.
bO = none; 1
= rare; 2 + = few; 3
= many.
computed tomographic; Pyr = pyrimethamine; sulfa = sulfadiazine;clinda = clindamycin;L = left; R
and developed or progressed after successful treatment
of toxoplasmosis in 9 others.
Neurodiagnostic Studies
CT scans were performed at presentation in 26 patients. Twenty-three received a contrast agent, including one who was studied with double-dose only
(Tables 1 and 3). Single-dose scans were negative in 3
patients, 2 of whom were studied 2 and 3 weeks before death; in the third patient, lesions were subse-
quently detected 3 weeks after the onset of symptoms
on a double-dose study. More than 40 mass lesions
were identified among 19 of the 22 patients studied
with a single dose of contrast material, including 12
patients with two or more lesions and 5 with bilateral
lesions. Each of 3 patients undergoing imaging without
contrast agent had a single hypodense lesion. Nearly
75% of the lesiops were located in the cerebral hemispheres, particularly in the frontopatietal area. Lesions
in the basal gangha and cerebellum were detected in
Navia et al: CNS Toxoplasmosis 227
Table 3. Computed Tomographic Scan Findings in Patients
with Cerebral Toxoplasmosis at Presentation
Table 2. Presenting Clinical Symptoms and Signs in 27
Patients with Central Nervous System Toxoplasmosis
Number of Patients
Symptoms and Signs
Focal manifestations
Hemiparesis (with aphasia, 4 )
Visual field loss
Cranial nerve palsies
Movement disorder
Nonfocal manifestations
Psychomotor retardation
Behavioral disturbance
Combined focal and nonfocal
Focal manifestations alone
Nonfocal manifestations alone
Neither focal nor nonfocal
AIDS retinopathy
Toxoplasmosis chorioretinitis
only 5 and 3 patients, respectively. Approximately
75% of the lesions showed contrast enhancement,
most frequently ring-enhancing and rarely homogeneous (Fig 1). Multiple hypodense lesions were the
only abnormahty in 3 patients, despite contrast administration (Fig 2). Delayed double-dose contrast CT
scan in 5 patients detected multiple lesions that were
not seen on single-dose scans in 4 patients and revealed a more clearly defined ring enhancement in the
other. Moderate to severe cerebral edema was present
in 13 patients. Other findings included cortical atrophy
with ventricular dilatation in 9 patients and ventricular
dilatation alone in one. In one patient, MRI (using a
superconducting 0.5 Tesla magnet) detected several
lesions after only a single lesion had been found in
previous single-dose and double-dose CT studies (Fig
CSF analysis performed in 2 1 patients showed protein elevations in 18, with a range of 5 1 to 208 mgdl
and a mean of 96 mg/dl. Nine patients had a mononuclear pleocytosis, with 4 to 8 cells/mm3 in 6 and greater
than 10 cells/mm3 in 4 (range, 24 to 67 cells/mm3).
One patient had an increase in cells from 8 to 61/mm3,
despite clinical improvement after 1 week of treat228 Annals of Neurology
Vol 19 No 3 March 1986
Number of Patients
Contrast agenta
Contrast-enhancing lesions
Ring enhancement
Homogeneous enhancement
Hypodense lesions
No contrast
Lesions identified
"Single injection of contrast agent only. One additional patient was
studied with a double dose only. His scan showed multiple enhancing lesions, but this result is not included.
ment. The CSF glucose value was mildly depressed in
3 patients (43, 4 2 , and 38 mgfdl, respectively).
A total of 6 open-brain biopsies were performed in
5 patients. They were initially interpreted as diagnostic
(organisms detected on H&E staining) in 3. One patient had two nondiagnostic biopsies. Subsequent review using additional sections and immunoperoxidase
staining showed organisms in all 5 patients. Transient
postoperative complications in 2 patients included focal seizures with worsening of presenting signs in one
and increased lethargy related to cerebral edema and
mass effect in the other.
Toxoplasma Serology
Toxoplasma serology was available in 25 patients at the
time of presentation and in 15 patients between 1 and
6 months before the onset of cerebral disease (Fig 4).
All patients were seropositive for IgG antibody, but
over a wide range of titers. Only 7 patients had titers of
1:1,024 or greater at onset, while 3 had titers of 1: 16
or below. Fourfold rises in titer were noted in only 5
Serum IgM antibody against T. gondii was detected
in only 2 of 13 patients tested, whereas complement
fixation testing yielded positive titers in 13 of 17 patients, with results ranging from 1:2 to 1:512, 1:8
being the most frequent titer. CSF determinations of
IgG anti-Toxoplasma antibody were positive in 9 of 13
patients, but most of these were only in undiluted or
1:2 dilution specimens. Two of 6 patients in whom
serial CSF and serum titers were available demonstrated a greater than fourfold rise in the CSF antibody
titer in the presence of unchanged serum titers.
Therapy and Outcome
Twenty-two patients received either pyrimethamine in
combination with sulfonamides (20 patients) or clindamycin (2 patients) as the initial form of treatment for
cerebral toxoplasmosis (Table 1). Clindamycin was
Fig 1. Contrast-enhanced computed tomographicscans of Patient
22, who presented with headache, left-sided numbness, and
ataxia. (a)A t presentation there was an irregularly shaped
ring-enhancing lesion in the left parietooccipital region (shown
on the right side) with surrounding edema. (S) After one week of
treatment with pyrimethamine and sulfadiazine, the ring enhancement was no longer present, although edema remined
prominent. (c)After two week of treatment, no contrast-enhancing lesion was defined and edema was reduced.
subsequently substituted for sulfadiazine in 2 patients
because of presumed sulfa-related complications, and
added to pyrimethamine in a third who had been taken
off sulfadiazine earlier in the disease course. Ten patients were treated with dexamethasone to relieve cerebral edema.
Eighteen patients responded favorably to anti-Toxoplasma therapy as judged by improvement in neurological signs or CT findings (Table 4). Clinical improvement occurred within 1 to 2 weeks after initiation of treatment in 16 patients, including 7 who improved within one day. Five of the 7 very rapid
responders also received dexamethasone. Improvement demonstrated on CT scan paralleled clinical response in 14 of 15 patients studied, including 8 of 9
who were scanned 1 to 2 weeks and all 6 who were
scanned 3 to 4 weeks after starting therapy (Fig 1).
Only 4 of these patients were receiving dexamethasone at the time. A repeat MRI scan in 1 patient demonstrated that the lesions had become smaller (Fig 3).
Fourteen of the 18 patients responding to treatment
survived for more than 2 months. Four of these patients experienced clinical relapse while being treated
with pyrimethamine alone. Two subsequently responded to reinstitution of sulfonamides, one improved spontaneously, and one died of intercurrent
Fig 2. Contrast-enbanced computed tomographic scan of Patient
6. This patient developed a subacute generalized encephalopathy
and a right-sided seizure. Multiple ill-defined areas of low density were seen. In this section there is compression of the left
fmntal horn related t o a deep mass lesion, a second lesion a&acent to the left occipital horn, and an additional lesion in the
right frontal region.
medical problems. However, 3 other patients maintained remission for 1 to 10 months while on pyrimethamine alone. Overall, 10 of the 14 responders
succumbed to other medical problems within 3 to 11
months. CT scans performed within 1 month before
death in 9 patients and within 3 months before death
Navia et al: CNS Toxoplasmosis
230 Annals of Neurology Vol 19 NO 3 March 1986
Table 4. Outcome in 27 Patients with AIDS
with Cerebral Toxoplasmosis
4096 -
2048 -
Favorable response
Survived >2 months
Survived <2 months
No response
No treatment
1024 L
512 -
Number o f Patients
6432 16 -
At Presentation
F i g 4. Serum IgG anti-Toxoplasma antibody titers. Shown are
the recz$rocals of serum dilutions from specimens obtained between 1 and 4 months before the onset of toxoplasmosis and at
the time of presentation with cerebral toxoplasmosis. Sabin-Feum a n dye test results are depicted by open squares, and serum
immunojuorescent antibody titers are shown by open circles in
cases in which only unpaired specimens were assessed and closed
circles when paired specimens were assayed simultaneously. Lines
connect results from individual patients.
in 1 patient showed complete resolution of focal abnormalities, with the exception of small hypodense lesions related to healed toxoplasmosis in 3; all 10 had
cortical atrophy. Of 4 remaining patients, one was subsequently lost to follow-up and the other 3 remained
stable on continued therapy 4 to 7 months after diagnosis.
Four other patients responded to therapy but died
within 2 months, 3 from intercurrent sepsis. The
fourth patient underwent several changes in treatment
because of drug-related complications and finally died
after developing status epilepticus.
4 F i g 3. Computed tomographic (CT) and magnetic resonance im-
aging (MRI) scans of Patient 27. A through E are CT and
MRI scans obtained at presentation and F is an MRI scan
taken 2 weeks afer treatment was initiated. (A) The non-contrast-enhanced C T scan shms an area of edema in the right
occipital lobe. (B) A double-dose scan shows vague ring enhancement of the right occipital lesion. (C)MRI image shows the
right occipital lesion and surrounding edema as well as a right
frontal lesion. (0)A higher cut on the MRI scan shows the
right occipital edema and an additional lesion in the lejl internal capsule, which in retrospect was vaguely seen on the CT scan
(Aand B). (E)An additional MRI cut shuws a Idt temporal
and three cerebellar lesions. (F) Two weeks after treatment was
begun, the temporal and cerebellar lesions are reduced in size.
Delay in establishing diagnosis contributed to the
lack of treatment response in 4 patients. In addition, 2
of these patients were receiving dexamethasone for 2
to 3 weeks before anti-Toxoplasma treatment was begun. Three of the 4 patients died within 3 days after
the institution of therapy, having exhibited fluctuating
neurological symptoms for 3 to 8 weeks prior to diagnosis. The fourth patient underwent two nondiagnostic
brain biopsies and died 2 weeks after an abbreviated
course of therapy was stopped (Patient 9, see later).
Five patients never received specific therapy. Three
were seropositive at 1:256, one at 1:128, and one
never had titers measured. Four had definite focal
neurological findings, but contrast CT scans failed to
reveal lesions in 2 while in each of the other 2 a noncontrast CT scan showed a single hypodense lesion.
One of these patients was a 59-year-old man not suspected of having AIDS whose CT scan was interpreted
as consistent with cerebral infarction. The fifth patient
was not evaluated neurologically. Confounding medical problems, including respiratory failure and infection in 2, adrenal insufficiency in 1, and sepsis with
renal failure in 2, obscured diagnosis and hampered
complete investigation in this group.
Neuropatbological Findings
Each of the 5 patients who underwent surgical biopsy
had shown ring-enhancing lesions on CT scans performed 1 to 7 days (mean, 3.8 days) earlier. Microscopical examination showed areas of necrosis surrounded by acute and chronic inflammatory cells,
reactive astrocytes, and macrophages (Fig 5). Vascular
proliferation and endothelial hyperplasia were prominent within the peripheral zone in all 5 patients.
Postmortem examination was performed in 16 patients. All had multiple abscesses, most frequently in
the cerebral and cerebellar cortex. The lesions were
grouped into three histological types based on degree
of tissue reaction: necrotizing, organizing, and chronic.
Necrotizing abscesses were the sole finding in 8 patients. Five of them had never received treatment,
while the remaining 3 were treated for less than 3 days.
A ninth patient also had necrotizing lesions that surrounded organizing abscesses. This patient (Patient 9)
Navia et
CNS Toxoplasmosis 231
Fig 5 . (A)Biopsy specimen from Patient 11 shows a necrotizing
abscess with necrosis (right) and infiltration of injammatory
cells and macrophages (lefi).A computed tomographic scan performed 1 day before surgey showed a ring-enhancing lesion.
(HCE; x 40.) (B) Higher-power micrograph demonstrates vascular prolifPration with endothelial cell hyperplasia and a
mixed-cell infiltrate consisting of mononuclear injammatory cells
and lipid-la& mucrophages. (HGE;origimf magnification,
x 100.)
232 Annals of Neurology Vol 19 No 3 March 1986
had received 2 weeks of treatment that had been discontinued 2 weeks before death. Necrotizing abscesses were characterized grossly by areas of softening
and discoloration with surrounding edema. Microscopical examination revealed poorly demarcated areas of
necrosis containing a variable number of petechiae. In
6 patients, the abscesses contained a mixed inflammatory cell infiltrate and lipid-laden macrophages, and
showed vascular proliferation. Small arteries surrounding the abscesses showed marked intimal proliferation
or frank necrosis of the arterial walls accompanied
by polymorphonuclear leukocytes and intraluminal
thrombosis. Inflammation, macrophage infiltration,
and vascular proliferation were scant in 2 patients and
absent in another (Fig 6A). In all 8 patients, routine
H&E-stained sections revealed many T. gondii tachyzoites located at the periphery of the abscesses and
within adjacent neuropil. Encysted bradyzoites also
were present but were numerous only in 3 patients.
Immunohistochemical stains using anti-Toxopkzsma
antiserum stained cell bodies of both the tachyzoites
and encysted bradyzoites (Fig 6B).
Organizing abscesses were present in 7 patients, all
of whom had been treated for 2 weeks or longer
(range, 2 weeks to 10 months). These lesions consisted
of large, well-demarcated areas of central coagulation
necrosis surrounded by a thin rim of tightly packed
lipid-laden macrophages. Cysts and tachyzoites were
adjacent to the organizing abscesses in 3 of the 7 patients. No organisms were seen in 3 patients, although
in Patient 11 a brain biopsy obtained 2 months before
death had demonstrated a necrotizing abscess containing numerous cysts and tachyzoites. In 1 patient only
cysts were identified.
Chronic abscesses were present in 6 patients, 5 of
whom also had organizing abscesses. These patients
had been treated for 4 weeks to 11 months. The
chronic abscesses were small (usually less than 0.5 cm
in diameter) cystic spaces that contained small numbers of lipid-laden and occasional hemosiderin-containing macrophages with surrounding gliosis. Rare
Toxoplasma cysts were noted in adjacent brain tissue in
three of these patients.
Additional central nervous system lesions included
microglial nodules (11 patients), a mixed cytomegalovirus-herpes simplex virus necrotizing ventriculoencephalitis (1 patient), Candida albicans abscesses (1
patient), primary central nervous system lymphoma
(1 patient), and vacuolar myelopathy (4 patients) [393.
T. gondii cysts were found on routine sections of
the heart, lung, or prostate in 3 patients.
Cerebral toxoplasmosis is the most common cause of
focal brain lesions in patients with AIDS r28, 32, 503.
in our series, Toxoplasma abscesses were present in
approximately 13% of patients with AIDS undergoing
postmortem examination; this compared with a lower
incidence of other focal brain lesions, including central
nervous system lymphoma (6%), progressive multifocal leukoencephalopathy (2%), and fungal abscesses (3%) (unpublished data, 1985). Because cerebral toxoplasmosis is due principally to reactivation of
endogenous infection acquired in the past 143, 451,
patients are seropositive before the development of
overt central nervous system disease. Based on the
prevalence of IFA blood titers in our overall population with AIDS and their incidence of cerebral toxoplasmosis, the risk of developing this complication in
seropositive individuals is estimated to be at least 30%
(Gold JWM: unpublished data, 1985). A higher incidence of cerebral toxoplasmosis among Haitian men
with AIDS probably reflects a greater prevalence of
endemic parasite infection in this population {40].
T. gondii is an obligate intracellular parasite that is
normally contained and eliminated by cell-mediated
mechanisms involving T lymphocytes and activated
macrophages E27, 361. It is a relatively frequent infection in the normal host but is either inapparent or
associated with a benign self-limiting course characterized by fever and lymphadenopathy 130, 433. However, in the presence of immunosuppression, a more
fulminant disease can occur, with the central nervous
system as the primary target [45, 523. The predilection
for T. gondii to reactivate in the brain has been well
established both clinically and experimentally. Ruskin
and Remington [45} noted central nervous system involvement in 45 of 81 reported cases of toxoplasmosis
in immunocompromised patients, while Frenkel and
associates [ 17) found that the central nervous system
was almost exclusively involved during relapsing toxoplasmosis induced in chronically infected experimental
animals subjected to immunosuppression. In our
series, Toxoplasma cysts were present in systemic organs in only 3 patients, although skeletal muscle was
not routinely examined. It has been suggested that the
predilection for recrudescence of the parasite in brain
may reflect the immunological privilege of the central
nervous system [53), but undefined aspects of the local
brain milieu probably contribute importantly to the
selective survival and local proliferation of the organism in concert with impaired cell-mediated immune
Development of central nervous system toxoplasmosis in patients with AIDS is not unexpected, given
the current understanding of the immunological impairment in this population. A variety of immune defects have been demonstrated in these patients, but
most prominent is a deficiency in the helpedinducer
subset of T lymphocytes [13, 151. This lymphocyte
subset is the primary target of the retrovirus causing
AIDS, called lymphadenopathy-associat~duirz/s (LAV)
Navia et al: CNS Toxoplasmosis 233
Fig 6. (A) Necrotizing abscesses show large and smallareas of
necrosis (arrows) with minimal vascular response and no inflammation in adjacent brain of Patient 6. A computed tomographic
scan perf med 2 week before death showed multiple hypodense
non-Eontrast-enhancing lesions. (HGE; X 40.) (B) Encysted
bradyzoztes (long arrows) and clusters of tachyzoites (short arrows) present in brain adjacent t o a necrotizing abscess, The
small blood vessel in the upper l ~istinjiltrated by inflammatoty
cells. The specimen is from Patient 9. (Immunoperoxiduse using
anti-Toxoplasma antiserum with hematoxylin counterstain;
original magnijkation, x 400.)
234 Annals of Neurology
Vol 19 No 3 March 1986
by one group of investigators 131 and human Tlymphotropic virus 111 (HTLV-111) by another [4 11.
Other functional defects in both cell-mediated and
humoral immunity have also been described, including
impaired cytotoxic T-cell activity, reduced natural
killer cell activity, impaired monocyte function, diminished production of immunoregulatory lymphokines
including gamma interferon, and impaired specific antibody responses 113, 151. More recently, Murray and
colleagues 138) have demonstrated that the defect in
intracellular killing of T. gondii in the AIDS monocyte
could be corrected by gamma interferon.
CtinicaE Presentation
Our patients exhibited a variable constellation of focal
and nonfocal central nervous system findings. The severity of their illnesses at onset ranged from one patient who presented with headache only to several with
rapidly evolving coma. The relative prominence of focal versus encephalitic symptoms and signs in individual patients presumably reflected the number and size
of the cerebral lesions, the number of actively proliferating organisms, and the host tissue response, including vascular occlusion and hemorrhage. Nearly
90% of the patients exhibited focal findings, although
in several these were mild and largely overshadowed
by more generalized cerebral dysfunction. Among the
focal features, hemispheric signs predominated, particularly the development of hemiparesis and aphasia. As
noted by others, clinical dysfunction of posterior fossa
structures and basal ganglia was relatively uncommon
[8, 20,49, 561, despite autopsy lesions in one or more
of these sites in several patients. The major encephalitic manifestations were generalized confusion
and decreased arousal, the latrer ranging from mild
lethargy to coma.
Two-thirds of the patients in this series exhibited
cognitive impairment with preserved consciousness
either before the onset of toxoplasmosis or after successful treatment. In many of these patients, the clinical picture resembled the dementia syndrome found in
other patients with AIDS (Navia, Jordan, Price: unpublished observations, 1985), in whom the CT scan characteristically shows diffuse cortical atrophy and ventricular enlargement, as also noted in most of the patients
in the present series. The major pathological abnormalities in patients with AIDS dementia are found in the
white matter and subcortical structures (Navia, Cho,
Petito, Price; unpublished observations, 1985). The
identification of LAV/HTLV-I11 nucleic acid [47) and,
more recently, retrovirus particles in the brains of
these patients { 121 suggests that this disease results
from direct infection of the brain by LAV/HTLV-111.
Clinical differentiation of AIDS dementia from active
toxoplasmosis can generally be made on the basis of
the slower evolution and preservation of consciousness
in the former condition compared with the subacute or
acute course and accompanying impairment of consciousness in the majority of confused patients with
evolving toxoplasmosis. However, since the two conditions frequently coexisted, the underlying AIDS dementia may have contributed to the high incidence of
general cerebral dysfunction noted in our patients. In
some, underlying moderate to severe AIDS dementia
obscured the onset and delayed the diagnosis of toxoplasmosis.
In our series, the correct diagnosis was made promptly
in 18 patients, was delayed in 4 , and missed in 5. However, retrospective review of the 9 patients with delayed or wrong diagnosis indicates that either correct
interpretation of their clinical findings, CT scan results,
and serology or more rigorous pursuit of diagnosis
could have allowed an accurate conclusion.
Our results confirm the usefulness of the CT scan in
diagnosis [9, 37, 42, 51). All but 3 of those patients
scanned had clear focal lesions, the majority of which
showed peripheral ring enhancement. These lesions
were most frequently located in the cortex and less
often in deep gray matter structures, including the
basal ganglia, where greater involvement has been reported in other series [42). Of note, contrast-enhanced
CT scan failed to show enhancement of lesions in 3
patients. The reason for this is not entirely clear, but
correlation of CT findings with the histopathological
characteristics of the biopsied patients and those patients who died shortly after scans were performed
suggests that local vascular proliferation and associated
inflammation surrounding the abscesses may be necessary for contrast enhancement [4, 9-11]. Thus,
the 5 biopsied patients all exhibited contrast enhancement of the sampled lesions and showed prominent
tissue response, including inflammation, macrophage
infiltration, and vascular proliferation associated with
endothelial hyperplasia. In contrast, the 2 patients with
nonenhancing lesions who died acutely had little or no
vascular hyperplasia at the edge of the lesions, although inflammation was prominent in one.
Whether because of the paucity of inflammation,
less vigorous vascular proliferation [9-111, or small
lesion size [19}, the CT scan considerably underestimated the number of lesions eventually noted at
postmortem examination in most of our patients. Double-dose scanning increased the number of lesions detected, indicating the value of this technique C42). Preliminary results of MRI scanning in 1 patient in this
series and in 2 more recent patients (unpublished observations, 1985) suggest its superiority over CT scanning. MRI appears to more sensitively detect the
disseminated multiple abscesses characteristic of the
disorder. This allows more accurate differentiation
Navia et al: CNS Toxoplasmosis
from other focal lesions in this group of patients, particularly from primary central nervous system lymphoma 19, 291.
With appropriate interpretation, Toxoplasma serology was diagnostically useful in our patients. Although
neither high nor rising titers were present in the majority, all patients were seropositive both at the time of
diagnosis and anteceding the onset of symptoms by
weeks or months, as previously reported C32, 57).
Thus, less than one-third of our patients had IgG titers
greater than or equal to 1:1,024, and only 5 exhibited
a significant (fourfold) rise. Of particular note, our laboratory initially began IFA titrations at a 1:16 dilution,
and therefore 2 of our patients were considered
seronegative until specimens were retitrated to include
lower dilutions, yielding final titers of 1:4 and 1:s.
Based on this experience, titrations now routinely begin at a serum dilution of 1:2. However, at least 1
patient with cerebral toxoplasmosis with negative
serum titers has been reported C321. Serum IgM and
complement fixation titers, as well as CSF IgG titers,
were not generally of additional help, and we have
abandoned their routine use.
Treatment and Outcome
The reversibility of both neurological deficits and CT
abnormalities in the majority of treated patients was
remarkable for its rapidity and extent. In general, the
level of consciousness, number of lesions on CT scan,
abnormalities in CSF, and magnitude of serum Toxoplasma titers had no evident bearing on outcome.
Thus, 2 patients who were obtunded on presentation
and 1 patient with an antibody titer higher than
1:16,000 and multiple bilateral lesions on CT scan
showed prompt clinical and radiographic improvement. Patients who responded to treatment had symptoms for 1 day to 4 weeks (mean, 1.7 weeks), while
nonresponders exhibited symptoms for 1 to 5 weeks
(mean, 3.3 weeks), indicating that failure to consider
the diagnosis and initiate treatment was probably the
most important reason for poor outcome. The higher
incidence of hypodense lesions in nonresponders (2
out of 3 given contrast material) compared with responders (6%) may in part be secondary to diagnostic
difficulty and delay in the former group, although the
less vigorous host response underlying the lack of contrast enhancement may also have contributed more directly to their poor outcome.
The currently recommended treatment for cerebral toxoplasmosis is a combination therapy of pyrimethamine and sulfonamides. Although the use of
clindamycin as an alternative to sulfonamides remains
controversial {32], its use in 5 of our patients, including one who was treated for 6 months, in conjunction
with pyrimethamine did not result in relapse. Whether
this reflected the therapeutic efficacy of pyrimethm i n e alone needs to be determined. However, 4 of
236 Annals of Neurology Vol 19 No 3 March 1986
7 patients treated solely with pyrimethamine developed recurrent symptoms. Complications of therapy, relatively frequent in this group of patients,
included leukopenia and skin rash that remitted on
withdrawal of the offending drug. Recurrences of
toxoplasmosis after drug reduction or alteration occurred in several instances, indicating the need for
continued treatment in these patients.
The use of corticosteroids in cerebral toxoplasmosis
is problematic because they impair cell-mediated responses not only against T . gondiz but also against
other organisms to which patients with AIDS are susceptible 114, 341. Dexamethasone was given to reduce
cerebral edema and appeared to contribute to early
resolution of neurological deficits in some patients.
However, in 2 patients corticosteroid treatment for
other conditions may have precipitated or exacerbated
overt cerebral infection. In general, we are very reluctant to give corticosteroids to patients with AIDS who
are already impaired. In instances when they appear
necessary, treatment should be as brief as possible,
with rapid tapering of dosage.
Neuropathologzcal Characteristics
Histopathological analysis of 19 of our 27 patients provided a view of the evolution of Toxophsma lesions in
relation to the patient's clinical course, CT scan results,
and the effects of therapy. Pathological findings at
postmortem examination in those who died after brief
or no therapy, as well as biopsy results, showed that
the earliest stage of central nervous system infection included necrotizing lesions containing a variable
amount of inflammation and vascular reaction. Previous reports have noted similar acute findings C18, 19,
52). Variation in the extent of local inflammation,
which included 2 patients with minimal or no inflammation, suggests that brain necrosis depended less on
host inflammatory responses than on a direct toxic effect of the proliferating organism 1191. In those patients who were either untreated or received less than
1 week of treatment, tachyzoites were generally abundant and typically were located in the periphery of the
expanding necrotic lesions. Thrombosis of blood vessels and petechial hemorrhages may have contributed
to the abrupt onset or fluctuation in clinical symptoms
in some patients. Whether antibody and immune complexes [48} are involved in the vascular occlusions is
unknown, but the finding of low antibody titers in 1
patient with these findings may suggest that they do
not have a major role.
Subsequent organization noted in patients treated
for at least 2 to 4 weeks involved the formation of
cystic cavities without the development of a fibrous
capsule, as occurs with bacterial abscess l211. In these
severely immunocompromised patients, drug therapy
was required to halt progressive necrosis and allow
abscess organization with the eventual formation of
cysts. In all but 2 patients who were treated for more
than several days, tachyzoites were effectively reduced
or eradicated. One of these exceptions was Patient 9,
who had been treated for 2 weeks, after which treatment was stopped over the 2-week interval prior to
death. The presence of organizing abscesses surrounded by areas of necrosis with numerous free
tachyzoites in this patient suggests that T . gondii proliferation had reemerged after initial control. In the
other patient, 4 weeks of therapy resulted in the detection of only a few scattered organisms. Tachyzoites
were absent and encysted organisms were rare in association with the chronic abscesses. However, bradyzoites did persist in 1 patient despite 1 year of treatment, warning that discontinued therapy is likely to
result in recrudescence.
Conclusions and Recommendations
Central nervous system toxoplasmosis is a curable
complication of AIDS. Early diagnosis and prompt
therapy are important in preventing mortality and reducing both early and late morbidity. Diagnosis usually
is not difficult but may be a problem in a minority of
cases. We emphasize the following points. (1)Cerebral
toxoplasmosis is the most common cause of focal central nervous system disease complicating AIDS and
may eventually afflict 10 to 15% of such patients. (2)
Its clinical picture is variable, ranging from headache
and fever to severe focal deficit or coma. Aggressive
neurological evaluation of central nervous system complaints in patients with AIDS is warranted, including
CT scan (or, when available, MRI) and lumbar puncture. Particular attention should be directed to patients
with focal abnormalities or new onset of headache, and
to those with subacutely evolving signs, including an
impaired level of arousal. (3) Because the disease represents reactivation of prior infection, we recommend
that patients particularly at risk be identified by obtaining serum IgG titers early in the course of AIDS or the
AIDS-related complex. Of principal importance in
diagnosis is whether patients are seropositive, not
whether titers are high or rising. However, depending
on the sensitivity of the laboratory methods employed,
a very low titer or even a negative serum titer does not
fully exclude the diagnosis of cerebral toxoplasmosis.
(4) The CT scan is currently the most helpful diagnostic test in general use. Most frequently, CT lesions
are characterized by ringlike contrast enhancement,
but in some patients homogeneous enhancement, absence of enhancement, or, rarely, no lesions may be
seen. Double-dose contrast CT and MRI scans appear
to increase detection of lesions. (5) Response to treatment with pyrimethamine and a sulfonamide is sufficiently rapid and effective in most patients to justify
therapeutic trial as a principal means of diagnosis. Previous reports have recommended brain biopsy 131,
357, but because of the potential morbidity and false-
negative results of this procedure, in most cases biopsy
is not warranted. Only when therapy fails to induce
clinical or CT scan improvement after 1 to 2 weeks do
we now recommend brain biopsy. Exceptions may be
necessary when the clinical picture is atypical, for
example, when serology is negative or the CT scan
fails to show characteristic ring-enhancing lesions. If
a biopsy is performed, immunoperoxidase staining
should be used to supplement routine histology [7};
this method facilitates detection of organisms and, to
date, we have not encountered false-positive results.
(6) To assure continued remission, prolonged therapy,
probably for the rest of the patient's life, is needed in
these individuals, who unfortunately continue to suffer
progressive immunosuppression.
This study was supported in part by Research Grant A01 59 from the
New York State AIDS Institute.
We thank Adele Ahronheim for preparation of this manuscript and
Dr Henry Murray for providing us with the anti-Toxoplasm antiserum for immunoperoxidase studies.
1. Alonso R, Heiman-Patterson T, Mancall EL Cerebral toxoplas-
mosis in acquired immune deficiency syndrome. Arch Neurol
41:321-323, 1984
2. Anderson JSP, Atlas E, Ahern MJ, Weisbrot IM: Central nervous system toxoplasmosis in homosexual men. Am J Med
75~877-881, 1983
3. Barre-Sinoussi F, Chermann JC, Rey F, et al: Isolation of a Tlymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 2205368-870,
4. Britt RH, Enzmann DR, Yeager AS: Neuropathological and
computerized tomographic findings in experimental brain abscess. J Neurosurg 55:590-603, 1981
5. Britton CB, Miller JR Neurological complications in acquired
immunodeficiency syndrome (AIDS). Neurol Clin 2:3 15-339,
6. Carey RM, Kimball AC, Armstrong D, Lieberman PH: Toxoplasmosis-clinical experiences in a cancer hospital. Am J Med
54:30-38, 1973
7. Conley FK, Jenkins KA, Remington JS: Toxoplasma gondii infection of the central nervous system-use of the peroxidaseantiperoxidase method to demonstrate toxophsma in formalin
fixed paraffin embedded tissue sections. Hum Pathol 12:690698, 1981
8. Delaney P, Neeley SM, Schwartz R. Fatal CNS toxoplasmosis
in a homosexual man. Neurology (NY) 33:926-927, 1983
9. Enzmann DR Imaging of infections and inflammation of the
C N S computed tomography, ultrasound, and nuclear magnetic
resonance. In New York, Raven, 1984, pp 259-308
10. Entmann DR, Brant-Zawadtki M, Britt RH: CT of central nervous system infections in immunocompromised patients. Am J
Neuroradiol 1:239-243, 1980
11. Entmann DR, Britt RH, Yeager AS: Experimental brain abscess
evolution: computed tomographic and neuropathologic correlation. Radiology 133:113-122, 1979
12. Epstein LG, Sharer LR, Cho E-S, et al: HTLV-IIULAV-like
retrovirus particles in the brains of patients with AIDS encephalopathy. AIDS Res 1:447-454, 1985
_ _
Navia et al: CNS Toxoplasmosis 237
13. Fauci AS: Immunologic abnormalities in the acquired immunodeficiency syndrome (AIDS). Clin Res 32:491-499, 1984
14. Fauci AS, Dale DC, Balow JE: Glucosteroid therapy: mechanisms of action and clinical considerations. Ann Intern Med
84:304-315, 1976
15. Fauci AS, Macher AM, Long0 DL, et al: Acquired immunodeficiency syndrome: epidemiologic, clinical, immunologic,
and therapeutic considerations. Ann Intern Med 10092-106,
16. Feldman HA, Lamb GA: A micromodification of the Toxoplasma dye test. J Parasitol 52:415, 1966
17. Frenkel JK, Nelson BM, Arias-Stella J: Immunosuppression
and toxoplasmic encephalitis. Hum Pathol 697-1 11, 1975
18. Ghatak NR, Poon P, Zimmerman HM: Toxoplasmosis of the
central nervous system in the adult. Arch Pathol 89:337-348,
19. Ghatak NR, Sawyer DR: A morphologic study of opportunistic
cerebral toxoplasmosis. Acta Neuropathol (Berl) 42:2 17-22 1,
20. Greenlee JE, Johnson WD, Campa JF, et al: Adult toxoplasmosis presenting as polymyositis and cerebellar ataxia. Ann Intern Med 82:367-371, 1975
21. Hakes TB, Armstrong D: Toxoplasmosis-problems in diagnosis and treatment. Cancer 52:1535-1540, 1983
22. Harriman DGF: Bacterial infections of the central nervous
system. In Adams JH, Corsellis JAN, Ducher LW (eds):
Greenfield’s Neuropathology. New York, Wiley, 1984, pp
23. Hauser WE, Luft BJ, Conley FK, Remington JS: Centralnervous-system toxoplasmosis in homosexual and heterosexual
adults. N Engl J Med 307:498-499, 1982
24. Hooper DC, Pruitt AA, Rubin RH: Central nervous system
infection in the chronically immunosuppressed. Medicine
64:166-188, 1982
25. Horowitz SL, Bentson JR, Benson DF, et al: CNS toxoplasmosis in acquired immunodeficiency syndrome. Arch Neurol
401649-652, 1983
26. Hsu S-M, Raine L, Fanger H: Use of avidin-biotin-peroxidase
complex (ABC) in immunoperoxidase techniques: a comparison
between ABC and unlabeled antibody (PAP) procedures.J Histochem Cytochem 2’9577-580, 1981
27. Johnson WD: Chronological development of cellular immunity
in human toxoplasmosis. Infect Immun 33948-949, 1981
28. Jordan BD, Navia BA, Petito C, et al: Neurological syndromes
complicating AIDS. Front Radiat Ther Onc 19:82-87, 1985
29. Kazner E, Wilske J, Steinhoff H , Stochdorph 0: Computerassisted tomography in primary malignant lymphomas of the
brain. J Comput Assist Tomogr 2:125-134, 1978
30. Krick JA, Remington JS: Toxoplasmosis in the adult-an overview. N Engl J Med 298:550-553, 1978
31. Levy RM, Pons VG, Rosenblum ML: Central nervous system
mass lesions in the acquired immunodeficiency syndrome
(AIDS). J Neurosurg 619-16, 1984
32. Luft BJ, Brooks RG, Conley FK, et al: Toxoplasmic encephalitis
in patients with acquired immune deficiency syndrome. JAMA
252:913-917, 1984
33. Luft BJ, Conley F, Remington JS, et al: Outbreak of central
nervous system toxoplasmosis in Western Europe and North
America. Lancet 1:781-784, 1983
34. Masur H, Murray HW, Jones TC: Effect of hydrocortisone on
macrophage response to lymphokine. Infect Immun 35:709714, 1982
35. McLeod R, Berry PF, Marshall WH, et al: Toxoplasmosis presenting as brain abscesses-diagnosis by computerized tomography and cytology of aspirated purulent material. Am J Med
67:711-714, 1979
36. McLeod R, Remington JS: Influence of infection with Toxo-
238 Annals of Neurology Vol 19 No 3
March 1986
pkzsma on macrophage function, and role of macrophages in
resistance to Toxopkzsma. Am J Trop Med Hyg 26:170-185,
37. Menges H-W, Fischer E, Valavanis A, Schubiger 0: Cerebral
toxoplasmosis in the adult. J Comput Assist Tomogr 3:413416, 1979
38. Murray HW, Rubin BY, Masur H , et al: Impaired production
of lymphokines and immune (gamma) interferon in the acquired
immunodeficiency syndrome. N Engl J Med 3 10:883-889,
39. Petito CK, Navia BA, Cho E-S, et d.Myelopathy pathologically
resembling subacute combined degeneration in patients with
acquired immunodeficiency syndrome (AIDS). N Engl J Med
312:874-879, 1985
40. Pitchenik AE, Fischl MA, Dickinson GM, et al: Opportunistic
infections and Kaposi’s sarcoma among Haitians: evidence of a
new acquired immunodeficiency state. Ann Intern Med
98:277-284, 1983
41. Popovic M, Sarngadharan MG, Read E, Gallo RC: Detection,
isolation, and continuous production of cytopathic retroviruses
(HTLV-111) from patients with AIDS and pre-AIDS. Science
224~497-500, 1984
42. Post MJD, Chan JC, Hensley GT, et al: Toxoplasma encephalitis
in Haitian adults with acquired immunodeficiency syndrome: a
clinical-pathologic-CT correlation. Am J Neuroradiol 4: 155162, 1983
43. Remington JS, Jacobs L, Kaufman HE: Toxoplasmosis in the
adult. N Engl J Med 262:180-186, 1960
44. Remington JS, Miller MJ, Brownlee I: IgM antibodies in acute
toxoplasmosis: 11. Prevalence and significance in acquired cases.
J Lab Clin Med 71:855-866, 1968
45. Ruskin J, Remington JS: Toxoplasmosis in the compromised
host. Ann Intern Med 84:193-199, 1976
46. Ryning FW,Mills J: Pneumocystis carinii, Toxoplasma gondii, cytomegalovirus and the compromised host. West J Med 130:1834, 1979
47. Shaw GM, Harper ME, Hahn BH, et al: HTLV-111 infection in
brains of children and adults with AIDS encephalopathy. Science 227:177-182, 1985
48. Siegal JP, Remington JS: Circulating immune complexes in
toxoplasmosis: detection and clinical correlates. Clin Exp Immunol 52:157-163, 1983
49. Slavick HE, Lipman IJ: Brain stem toxoplasmosis complicating
Hodgkin’s disease. Arch Neurol 34:636-637, 1977
50. Snider WD, Simpson DM, Nielsen S, et al: Neurological complications of acquired immune deficiency syndrome: analysis of
50 patients. Ann Neurol 14:403-418, 1983
51. Summerfield GP: Demonstration of lesions of cerebral toxoplasmosis by computerized tomography. Postgrad Med J
56:112-114, 1980
52. Townsend JJ, Wolinsky JS, Baringer JR, Johnson PC: Acquired
toxoplasmosis-a neglected cause of treatable nervous system
disease. Arch Neurol 32:335-343, 1975
53. Van Thiel PH: The parasitology of toxoplasmosis in the central
nervous system. Psychiatr Neurol Neurochir 697-13, 1966
54. Vietzke WM, Gelderman AH, Grimley PM, Valsamis MP:
Toxoplasmosis complicating malignancy-experience
at the
National Cancer Institute. Cancer 21:816-827, 1968
55. Vilaseca J, Arnau JM, Bacardo R, et al: Kaposi’s sarcoma and
Toxoplasma gondit brain abscess in a Spanish homosexual. Lancet
1:572, 1982
56. Wilson WB, Sharpe JA, Deck JHN: Cerebral blindness and
oculomotor nerve palsies in toxoplasmosis. Am J Ophthalmol
89~714-718, 1980
57. Wong B, Gold JWM, Brown A, et al: Central nervous system
toxoplasmosis in homosexual men and parented drug abusers.
Ann Intern Med 100:36-42, 1984
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