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.