566 M. Wasay et al. / Clinical Neurology and Neurosurgery 111 (2009) 565–567
Baseline characteristics of patients.
Variable Preoperative (n = 11) Postoperative (n = 14) P
Mean age ± S.D. 51 ± 17 52 ± 20 >0.896
Male/female 7/4 10/4 >0.999
Average course duration (S.D.) 3 weeks (±1.5) 4 weeks (±1.7) >0.136
Coma at presentation 2 (18%) 2 (14%) >0.999
Immune suppression 3 (27%) 2 (14%) >0.623
Solitary abcess 9 (82%) 12 (86%) >0.999
Multiple abcessess 2 (18%) 2 (14%)
Interval between presentation and surgery (days) (S.D.) 5 days (±3.6) 4 days (±2.9) >0.447
Outcome of patients.
Variable Preoperative (n = 11) Postoperative (n = 14) P
Overall outcome <0.001
Death 0 10
Improved 7 1
No change 4 2
Worsening 0 1
Mean length of stay (days) (S.D.) 9 (±4.5) 14 (±6) <0.029
surgery in 2 patients and was administered after surgical proce-
dure in 10 patients. Fisher Exact test was used for preoperative and
postoperative groups for treatment used and different outcomes.
Independent samples t-test was used to compare the two treat-
ments for mean age, course duration, interval between presentation
and surgery, and length of hospital stay.
Twenty-ﬁve patients were included in the study. Cerebral
aspergillosis was largely a disease of immune competent people
(80%). Baseline clinical characteristics between the two treat-
ment groups (Table 1) were comparable i.e., age (P > 0.896),
gender (P > 0.999), coma at presentation (P > 0.999), immunosup-
pression (P > 0.623), number of abscesses (P > 0.999) and interval
between presentation and surgery (P > 0.447). Overall mortality
was 40% (n = 10 patients; 3 = itraconazole-treated patients and
7 = amphotericin-treated patients). The overall outcome was signif-
icantly better (P < 0.001) in patients treated with antifungal therapy
before surgery (Table 2). All nine patients who received itracona-
zole before their surgical procedure survived, while three out of
four subjects whose treatment was begun only after surgery died;
both patients who received preoperative amphotericin B survived
compared to only 3 of 10 whose treatment was delayed until after
surgery. All 11 patients who received antifungal therapy before
surgery survived, but only preoperative itraconazole treatment was
statistically associated with an improved survival compared to
delayed treatment. Mean length of stay in pre-treatment group was
shorter than post-treatment group (9 days versus 14 days, P < 0.02).
To our knowledge this is the ﬁrst study comparing utility of
pre-treatment antifungal therapy before surgical biopsy in patients
with cerebral aspergillosis. Amphotericin B-based therapy has poor
clinical efﬁcacy in cerebral aspergillosis . The administration of
antifungal therapy before surgery for CNS aspergillosis may have
a containment affect on brain lesions, and surgical exploration of
brain lesions without antifungal drugs on board may be harmful.
Overall outcome of these patients was better than most of the
published reports. One possible reason for this difference could be
the immune competent status of most of our patients. It is rare to
see cerebral aspergillosis in immune competent people in western
literature. The retrospective design, non-randomization of patients,
and small sample size are limitations of our study. It is possible
that longer duration of disease course in post-treatment group may
have affected the outcome because patients in pre-treatment group
sought medical attention a whole week earlier than post-treatment
group. The time interval between presentation and surgery was
not much difference in two groups. The empiric use of itracona-
zole was more common than empiric amphotericin. It could be
due to the fact that physician felt more comfortable in starting
empiric itraconazole as compared to empiric amphotericin while
waiting for the biopsy. Mean length of stay in pre-treatment group
was shorter than post-treatment group. This difference may have
important cost implications. The ratio of itraconazole/amphotericin
was 9/2 and 4/10 in preoperative and postoperative group respec-
tively. This difference was signiﬁcant (Fisher’s Exact test: P < 0.015).
This difference could be a potential source of bias. Other treat-
ment options for cerebral aspergillosis include voriconazole and
liposomal amphotericin but unfortunately these medications are
not available in Pakistan. Nonetheless, our ﬁndings suggest that
patients with suspected Apergillus brain abscess may beneﬁt from
pre-treatment with itraconazole before surgical biopsy of cerebral
or sinonasal lesions. A larger, randomized, controlled trial is needed
to conﬁrm our ﬁndings.
These ﬁndings were presented in preliminary form at the 59th
Annual meeting of American Academy of Neurology, Boston, USA
Authors are thankful to Prof. Steve Roach, Ohio State University,
Columbus, Ohio, USA, for review and valuable suggestions.
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