This study assessed the association between calcified neurocysticercosis lesions (CNLs) and antiepileptic drug-resistant epilepsy through a prospective analysis of 45 patients in South India with CNLs. The study divided patients into three groups: CNL alone (n=17), CNL with unilateral hippocampal sclerosis (HS) (n=18), and CNLs as incidental findings (n=10). Patients with CNL alone or CNL with HS who underwent resective surgery had good seizure outcomes, with 4 of 5 and 9 of 11 patients respectively becoming seizure-free. The study suggests CNLs can cause drug-resistant epilepsy and resective surgery may be an effective treatment for select patients

1. Epilepsia
Calcified neurocysticercosis lesions and
antiepileptic drug- resistant epilepsy: A
surgically remediable syndrome?
Chaturbhuj Rathore, Bejoy Thomas,
Chandrasekharan Kesavadas, Mathew
Abraham, and Kurupath Radhakrishnan
Epilepsia, 54(10):1815-1822, 2013
doi: 10.1111/epi.12349
Publised october, 2013.

2. BACKGROUND
• In contrast to association between acute symptomatic
seizures and neurocysticercosis, the association between
antiepileptic drug (AED)-resistant epilepsy and calcified
neurocysticercosis lesions (CNLs) is poorly understood
and controversial.
• The association between AED-resistant epilepsy and
CNLs, including the feasibility and outcome of resective
surgery.

3. Objectives
• To assess the causative role of CNL in AEDresistant epilepsy
• To study the factors that contribute to AED-resistant
epilepsy in patients with CNL
• To define the role of resective surgery in patients
with CNL and AED-resistant epilepsy.

4. STUDY DESIGN
• Prospective database at epilepsy surgery Centery
Care, SCTIMST.
• Genders Eligible for Study: Both
• AED-resistant epilepsy as persistent seizures(≥1
seizures /month) despite two adequate and tolerated
AED monotherapy trials and at least one duotherapy
trial.
• After excluding patients with calcified tumors,
vascular malformations, and tuberculomas.

5. Patients and Methods
• All the patients evaluated for AED-resistant epilepsy
from January 2001 to July 2010 at SCIMT and found to
have calcified lesion/s on imaging studies were selected
for this study.
• Clinical, neuroimaging, and interictal, ictal, and
intracranial electroencephalography (EEG) findings to
determine the association between CNL and epilepsy.

6. PARTICIPANTS:
• 45 patients who had CNL in a resident of an
endemic region.
• 18 patients had CNL plus unilateral HS and were
classified as the CNL with HS group.
• 27 patients who did not have HS, 10 patients had
causes other than CNL for their seizures (five had
malformations of cortical development, two had
nonepileptic seizures, two had severe mental
retardation, and one had benign rolandic epilepsy).

7. Continued…….
• 17 patients, in whom CNL was established to be
the causative lesion for AED-resistant seizures,
formed the CNL without HS (CNL alone) group.
• For the HS without CNL (HS alone) group,
randomly selected 36 patients with mesial
temporal lobe epilepsy with HS (MTLE-HS) who
had no other lesions on magnetic resonance
imaging (MRI), pathologically verified HS after
anterior temporal lobectomy, and were seizurefree for at least 5 years following surgery.

8.  CNL was diagnosed as the presence of solid, dense, supratentorial
calcification of 10 mm in diameter in a resident of an endemic
region
 Clinical evaluation
Age at onset of seizures.
Age at initial precipitating injury (IPI) its nature, duration of
epilepsy.
Clinical semiology of all seizure types, and any change in seizure
semiology during the course of illness.

9. • EEG
• At least 2 habitual seizures recorded.
• Minimum of 10 min of every hour during a 24-h
period.
• Only definite spikes or sharp waves were considered as
IEDs.
• F7, F8, T1, T2, T3, and T4 defined as temporal IEDs.

10. CT and MRI evaluation
•NCCT&CECT HEAD and a 1.5 T MRI
•Number and site of calcified lesion(s); size of lesions;
presence of surrounding gliosis as determined on T2weighted and FLAIR sequences; and presence of any
other potentially epileptogenic lesion including
hippocampal sclerosis (HS).

11. • HS defined as the presence of unequivocal atrophy
of the hippocampus with a corresponding increase in
the signal on T2-weighted and FLAIR sequences.

12. Additional tests
•SPECT, and intracranial monitoring.
•For calcified lesions, removal of the lesion along with one
centimeter of surrounding margin.
•All specimens histopathologically examined.
• Defined HS as the loss of neuronal cell population of ≥30%
CA1 sector of the hippocampal formation with or without
neuronal loss and gliosis involving other mesial temporal
structures.

13. Follow-up and seizure outcome
• At 3 months,1 year following surgery then yearly
afterwards.
•Seizure outcome at each year classified as seizurefree (free of all seizures and auras) or not seizure-free.
•All the operated patients had a minimum follow-up of
2 years.

14. RESULTS:
• From January 2001 to July 2010, a total of 3,895
patients with AED-resistant epilepsy .
• 51 patients had AED-resistant epilepsy and calcified
granulomatous lesions on imaging studies.
• 6 patients have calcified lesions related to previous
central nervous system tuberculosis, excluded from
study. The remaining 45 patients (24 male, 21 female)
fulfilled the inclusion criteria for CNL.

15. Cohort divided into three groups:
•CNL was the only imaging abnormality and it was
considered as the causative lesion for AED-resistant
epilepsy (group 1, n = 17)
•CNL associated with unilateral HS (group 2, n = 18)
•CNLs were considered as incidental lesions (group 3,
n = 10)

16. Comparison of group characteristics of
patients
Patient groups
Characteristic
CNL with HS N = 18
Intergroup comparisons p-valu
CNL alone N = 17
Febrile seizures, N
(%)
4 (22.2)
0
Age at initial
precipitating injury,
years (mean ± SD)
(95% CI)
5.8 ± 5.7 (3.0–8.6)
Age at onset of
habitual seizures,
years (mean ± SD)
(95% CI)
15.8 ± 6.7 (12.5–
19.1)
HS alone N = 36
19 (52.8)
CNL with HS vs. CNL
alone
CNL with HS
alone
0.103
0.043
12.7 ± 6.8 (9.2–16.2) 1.4 ± 1.0 (1.1–1.7)
0.003
0.041
12.7 ± 6.8 (9.2–16.2) 9.8 ± 5.8 (7.8–11.8)
0.183
0.002
Seizure clustering, N
5 (27.8)
(%)
7 (41.2)
2 (5.6)
0.488
0.034
Secondary
generalized seizures, 4 (22.2)
N (%)b
14 (82.4)
10 (27.8)
0.001
0.751
CNL within temporal
11 (61.1)
lobe, N (%)
2 (11.8)
–
0.004
–
Extratemporal/bitem
poral IED on EEG, N 9 (50.0)
(%)
15 (88.2)
3 (8.3)
0.027
0.001

17. CNL with HS versus HS alone
•CNL with HS had a lower incidence of typical febrile seizures,
older age at initial precipitating injury (IPI), more frequent
clustering of seizures, and older age of onset of habitual complex
partial seizures as compared with HS.
•CNL with HS had more extratemporal and bitemporal interictal
epileptiform discharges EEG as compared with patients with HS
alone.
• No difference between CNL with HS and HS alone groups in
frequency of secondary generalized seizures.

18. CNL with HS versus CNL alone
•CNL with HS had a lower age at the initial precipitating injury
and less frequent secondary generalized seizures as compared
with HS alone.
• 61.1% of patients with CNL with HS had the CNL within the
I/L temporal lobe, only 11.8% in the CNL alone had CNL within
the temporal lobe.
•More CNL alone patients had extratemporal/bitemporal interictal
epileptiform discharges as compared to those with CNL with HS.

19. Characteristics of patients with AED-resistant epilepsy and calcified neurocysticercal
lesion, who underwent surgery.
Age
Location of CNL
Age at 1st
seizure
Interictal epileptiform
Ictal
localization
Associated
lesion
Type of surgery &
outcome
27
Right frontal
9
Right frontal
Right frontal
none
Seizure-free following
lesionectomy
29
Right frontal
16
Right frontal
Right frontal
none
Seizure-free following
lesionectomy
19
Left posterior
temporal
11
Left temporal
Left posterior
none
Not seizure-free following
temporal lesionectomy
17
Right parietal
13
Bilateral temporal
Right
hemispheric
none
Seizure-free following
intracranial EEG and
lesionectomy
24
Left parietal
12
Left parietal ,left
temporal
Left parietal
none
Seizure-free following
lesionectomy
47
Left occipital
7
Right temporal
Left temporal
Left HS
Left ATL; not seizure-free
23
Right occipital
9
Right temporal
Right
temporal
Right HS
Right ATL; not seizurefree

20. Continued…
Age at 1st
seizure
5
Interictal epileptiform
Ictal localization
Right temporal
Right frontal,right
occipital,left temporal
10
21
Right hippocampus
25
Age
Location of CNL
Right temporal
Associated
lesion
Right HS
Type of surgery &
outcome
Right ATL; not seizure-free
22
Right parietal
33
Right temporal
Right temporal
Right HS
Right ATL; seizure-free
11
Bilateral temporal
Right temporal
Right HS
Right ATL with esionectomy;
seizure-free
Left hippocampus
16
Left temporal
Left temporal
Left HS
Left ATL with lesionectomy;
seizure-free
26
Right fusiform gyrus
4
Right temporal
Right temporal
Right HS
Right ATL with
lesionectomy; seizure-free
21
Right occipital
13
Right occipital,bilateral
temporal
Right hemispheric
Right HS
26
Left parietal
8
bilateral temporal,left
parietal
uncertain
Left HS
25
Right parietal
10
Right parietal, right
temporal
Right parietal
Right HS
Intracranial EEG showed
seizure origin from the lesion
and hippocampus; seizure-free
following tempora resection
and lesionectomy
Intracranial EEG showed
seizure origin from the lesion
and hippocampus; seizure-free
following temporal resection a
nd lesionectomy
Lesionectomy alone;, not
seizure-free

21. 15 patients underwent resective surgery.
Group 1
4 of 5 became seizure-free following lesionectomy alone.
Group 2
4 patients underwent anterior temporal lobectomy
(ATL) alone, of whom 1 became seizure-free; 5 underwent
ATL combined with removal of CNL all of them became
seizure-free, whereas 1 patient underwent lesionectomy alone
and did not become seizure-free.

22. Pathology
• H/E of lesions showed dense calcifications ,chronic
inflammatory infiltrates and reactive gliosis.
• All the hippocampal specimens showed classical
hippocampal sclerosis without inflammation.

23. DISCUSSION
• Genetic, parasitic, and environmental factors contribute to the
epileptogenesis in CNL,
• Intense inflammation and perilesional gliosis associated with
a higher risk of seizures and epilepsy.
• These results shows DRE caused by CNLs is a potentially
surgically remediable syndrome with a very good chance of
seizure freefollowing lesionectomy.
• Epileptogenicity in these patients is usually restricted to the
perilesional tissue.

24. LACUNAE
•
•
•
•
•
Highly selected group of patients.
These results cannot be generalized.
Only presence of CNL not responsible for epilepsy.
Not establish the definite cause-effect relationship.
Not provide the true estimate of AED-resistant epilepsy caused
by CNL.
• Longitudinal long-term follow-up studies of patients with
acute neurocysticercosis in endemic areas are required to
estimate of the AED-resistant epilepsy caused by CNL.

25. TAKE HOME MESSAGE
• This study highlights and supports surgical therapy in
patients of AED-drug resistant epilepsy with CNL
with HS and calcified NCC.

26. Applicability and application
• Is the study population relevant to my practice
and patients?
Yes
• Are the patients in my practice similar to those
in the study?
Yes

27. Relevance
• Is this problem common in my practice?
Yes
• Will this information require to change my
current practice?
• Yes

28. CRITICAL APPRAISAL
• Did study address the focused question ?
yes
• Was there a control group?
yes
• Were the groups comparable at baseline ?
No
• Was outcome measured by blind assessors ?
no

29. CRITICAL APPRAISAL
• Did the surgery make any significant difference
in the study?
yes
• How precise were the results ?
Precise enough.
• Are all clinically relevant outcome considered?
yes
• Can results be applied on our population ?
yes

31. CNL & HS: Surgical Outcome
Author
Country
Follow up
HS-CNL
(n)
HS
alone(n)
Leite et al
2000
Brazil
30 months
26 / 32
(81%)
23 / 30
Velasco et
.al 2006
Brazil
2 yrs
72%
78%
Chandra
et al 2010
India
?
4/4
(100%)
Ooi et al
2011
USA
5 yrs
Chung et
1998
Korea
2yrs
CNL
alone(n)
2/2
0/1
1 /1

32. CNL & Intractable Epilepsy
•
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•
•
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•
lesions and hippocampal sclerosis: potential dual pathology? Epilepsia 53, e60-62.
Chandra, P.S., Bal, C., Garg, A., Gaikwad, S., Prasad, K., Sharma, B.S., Sarkar, C., Singh, M.B.,
Padma, V.M., Tripathi, M., 2010. Surgery for medically intractable epilepsy due to
•
postinfectious etiologies. Epilepsia 51, 1097-1100.
Leite, J.P., Terra-Bustamante, V.C., Fernandes, R.M., Santos, A.C., Chimelli, L., Sakamoto,
A.C., Assirati, J.A., Takayanagui, O.M., 2000. Calcified neurocysticercotic lesions and
;1
;6 /18.
; 4 /6
.; 3/32
•
postsurgery seizure control in temporal lobe epilepsy. Neurology 55, 1485-1491
Velasco, T.R., Zanello, P.A., Dalmagro, C.L., Araujo, D., Jr., Santos, A.C., Bianchin, M.M.,
Alexandre, V., Jr., Walz, R., Assirati, J.A., Carlotti, C.G., Jr., Takayanagui, O.M., Sakamoto,
A.C., Leite, J.P., 2006. Calcified cysticercotic lesions and intractable epilepsy: a cross sectional
study of 512 patients. Journal of neurology, neurosurgery, and psychiatry 77, 485-488.;
cases.
some

33. Calcified neurocysticercotic lesions and postsurgery
seizure control in temporal lobe epilepsy
1.J.P. Leite, MD, PhD, V.C. Terra–Bustamante, MD, R.M. F. Fernandes, MD, PhD,
A.C. Santos, MD, PhD, L. Chimelli, MD, PhD, A.C. Sakamoto, MD, PhD, J.A. Assirati, MD and O.M. Takayanagui,
MD, PhD
doi: 10.1212/WNL.55.10.1485Neurology November 28, 2000 vol. 55 no.
10 1485-1491
The presence of CCL does not influence the clinical and pathologic profile of
patients with hippocampal atrophy. Clinical histories and postsurgical outcomes
were similar to those of patients with classic HS, suggesting that the CCL is
probably, in this set of patients, a coincidental pathology and does not have a role
in epileptogenesis.