Calcified neurocysticercosis lesions and
antiepileptic drug- resistant epilepsy: A
surgically remediable syndrome?
Chaturbhuj Rathore, Bejoy Thomas, Chandrasekharan Kesavadas, Mathew Abraham, and Kurupath RadhakrishnanEpilepsia, 54(10):1815-1822, 2013 doi: 10.1111/epi.12349 Publised october, 2013.
Epilepsia
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 resectivesurgery.
Objectives
• To assess the causative role of CNL in AED-
resistant 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.
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.
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.
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).
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 mesialtemporal 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 seizure-free for at least 5 years following surgery.
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.
• 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.
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 T2-
weighted and FLAIR sequences; and presence of any
other potentially epileptogenic lesion including
hippocampal sclerosis (HS).
• HS defined as the presence of unequivocal atrophy
of the hippocampus with a corresponding increase in
the signal on T2-weighted and FLAIR sequences.
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.
Follow-up and seizure outcome
• At 3 months,1 year following surgery then yearly
afterwards.
•Seizure outcome at each year classified as seizure-
free (free of all seizures and auras) or not seizure-free.
•All the operated patients had a minimum follow-up of
2 years.
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.
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)
CharacteristicPatient groups Intergroup comparisons p-value
CNL with HS N = 18 CNL alone N = 17 HS alone N = 36CNL with HS vs. CNL
alone
CNL with HS vs. HS
alone
Febrile seizures, N
(%)4 (22.2) 0 19 (52.8) 0.103 0.043
Age at initial
precipitating injury,
years (mean ± SD)
(95% CI)
5.8 ± 5.7 (3.0–8.6) 12.7 ± 6.8 (9.2–16.2) 1.4 ± 1.0 (1.1–1.7) 0.003 0.041
Age at onset of
habitual seizures,
years (mean ± SD)
(95% CI)
15.8 ± 6.7 (12.5–
19.1)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,
N (%)b
4 (22.2) 14 (82.4) 10 (27.8) 0.001 0.751
CNL within temporal
lobe, N (%)11 (61.1) 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
Perilesional gliosis 12 (66.7) 12 (70.6) – 1.000 –
Comparison of group characteristics of
patients
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.
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.
Characteristics of patients with AED-resistant epilepsy and calcified neurocysticercallesion, 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 seizure-
free
Continued…Age Location of CNL Age at 1st
seizure
Interictal epileptiform Ictal localization Associated
lesion
Type of surgery &
outcome
22 Right parietal 5 Right temporal Right temporal Right HS Right ATL; not seizure-free
33 Right frontal,right
occipital,left temporal
10 Right temporal Right temporal Right HS Right ATL; seizure-free
21 Right hippocampus 11 Bilateral temporal Right temporal Right HS Right ATL with esionectomy;
seizure-free
25 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 Intracranial EEG showed
seizure origin from the lesion
and hippocampus; seizure-free
following tempora resection
and lesionectomy
26 Left parietal 8 bilateral temporal,left
parietal
uncertain Left HS Intracranial EEG showed
seizure origin from the lesion
and hippocampus; seizure-free
following temporal resection a
nd lesionectomy
25 Right parietal 10 Right parietal, right
temporal
Right parietal Right HS Lesionectomyalone;, not
seizure-free
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.
Pathology
• H/E of lesions showed dense calcifications ,chronic
inflammatory infiltrates and reactive gliosis.
• All the hippocampal specimens showed classical
hippocampal sclerosis without inflammation.
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.
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.
TAKE HOME MESSAGE
• This study highlights and supports surgical therapy in
patients of AED-drug resistant epilepsy with CNL
with HS and calcified NCC.
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
Relevance
• Is this problem common in my practice?
Yes
• Will this information require to change my current practice?
• Yes
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
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
CNL & HS: Surgical Outcome
Author Country Follow up HS-CNL (n)
HS alone(n)
CNL 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%)
2/2
Ooi et al2011
USA 5 yrs 0/1
Chung et 1998
Korea 2yrs 1 /1
CNL & Intractable Epilepsy
• Chung, C.K., Lee, S.K., Chi, J.G., 1998. Temporal lobe epilepsy caused by intrahippocampal
• calcified cysticercus: a case report. Journal of Korean medical science 13, 445-448. ;1 • Rathore, C., Thomas, B., Kesavadas, C., Radhakrishnan, K., 2012. Calcified neurocysticercosis
lesions and hippocampal sclerosis: potential dual pathology? Epilepsia 53, e60-62. ;6 /18. • 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. ; 4 /6 • 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
postsurgery seizure control in temporal lobe epilepsy. Neurology 55, 1485-1491 .; 3/32• 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.; some
cases.
Calcified neurocysticercotic lesions and postsurgeryseizure 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.