Memory, executive function and language function are similarly impaired in both temporal and extra temporal refractory epilepsy—A prospective study

Epilepsy Research (2015) 109, 72—80

journal homepage: www.elsevier.com/locate/epilepsyres

Memory, executive function and language function are similarly impaired in both temporal and extra temporal refractory epilepsy—–A prospective study Vinod K. Rai, Garima Shukla ∗, Mohammad Afsar, Shivani Poornima, R.M. Pandey, Neha Rai, Vinay Goyal, Achal Srivastava, Deepti Vibha, Madhuri Behari Department of Neurology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India Received 18 March 2014; received in revised form 18 September 2014; accepted 29 September 2014 Available online 13 October 2014

KEYWORDS Memory; Executive function; Language; Extra temporal; Refractory epilepsy

Summary Introduction: Cognitive impairment has long been recognized as a co-morbidity or sequel to refractory epilepsy. This study was conducted to evaluate the degree and selectivity of involvement of memory, language and executive functions performance among patients with temporal (TLE) versus extratemporal epilepsy (ETLE). Methods: We prospectively enrolled adolescent and adult patients with medically refractory focal epilepsy, who had undergone pre-surgical evaluation. Language, memory and executive function assessment was done using Western Aphasia Battery, PGI memory scale and battery of four executive function tests (trail making test A & B, digit symbol test, Stroop Task and verbal fluency test), respectively. Results: Among102 patients enrolled (TLE-59, ETLE-43), mean age of patients 23.04 ± 8.3 years, 83 (82%) had impairment of more than one cognitive domain and 21 (21%) had all three domains involved. Severely impaired memory scores were found in 8.6% patients with MTLE-HS, 8% of the rest of the patients with TLE and 7% patients with ETLE. The differences in the mean scores were also not found statistically significant (p = 0.669). Naming impairment was the most common language abnormality, although all aphasia subscores were similar for the ETLE and TLE groups. Executive function impairment was the most common cognitive domain affected.

∗ Corresponding author at: Department of Neurology, Room no 2, 6th Floor, Neurosciences Centre, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India. Tel.: +91 011 26593785. E-mail addresses: vinod [email protected] (V.K. Rai), [email protected] (G. Shukla), [email protected] (M. Afsar), [email protected] (S. Poornima), [email protected] (R.M. Pandey), [email protected] (N. Rai), [email protected] (V. Goyal), [email protected] (A. Srivastava), [email protected] (D. Vibha), [email protected] (M. Behari).

http://dx.doi.org/10.1016/j.eplepsyres.2014.09.031 0920-1211/© 2014 Elsevier B.V. All rights reserved.

Memory, executive function and language function are similarly impaired in both temporal and extra

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Overall performance on executive function tests was found impaired in almost all patients of both groups without any significant inter-group difference, except on Trail-A test, which revealed better results in patients with mTLE-HS as compared to all other sub-groups. Conclusion: Our study shows that impairment of memory, language and executive function is common among patients with drug refractory epilepsy. The most prevalent impairment is in executive function. There is no significant difference in the degree, prevalence or selectivity of impairment in either of the three domains, between the TLE versus ETLE groups. © 2014 Elsevier B.V. All rights reserved.

Introduction Epilepsy is one of the most prevalent neurological disorders and the most common serious brain disorder worldwide with no age, racial, social class, neither national nor geographic boundaries. ILAE/IBE/WHO Global Campaign (2001) estimates around 50 million people have epilepsy worldwide, 85% of which live in developing countries, with prevalence range between 5 and 40 per 1000 persons. Nearly 20% to 30% of patients with epilepsy have seizures that are refractory to medical treatment. Prevalence of refractory epilepsy varies from 9% to 35% in different studies because of different criteria used to define refractoriness (Berg, 2009; French, 2006; Thompson and Duncan, 2005). Epilepsy is associated with significantly increased morbidity and mortality, which is higher than in the general population (Gaitatzi and Sander, 2004). Cognitive impairment has long been recognized as a comorbidity or sequel to refractory epilepsy. The causes for this can be multifactorial, e.g. underlying pathology, high frequency of seizures, medications and also, surgery. Studies indicate the association of cognitive impairment with factors like age of onset, seizure type, seizure frequency and localization of the seizure focus, however, there is variation in the strength of association of these factors, reported in different studies (Lah et al., 2006; Hamed, 2009). Recent literature suggests transition from a long-standing focus on the relationship between cognitive function and clinical epilepsy features to one linking cognitive impairment to underlying anatomic, metabolic, and other neurobiologic correlates of the epilepsies (Hermann et al., 2009). Memory and language impairment have frequently been reported among patients with temporal lobe epilepsy, yet cognitive impairment in these patients can be much more widespread (Thompson and Duncan, 2005). Neuropsychological impairment of chronic TLE patients is widespread involving not only memory, but also intelligence quotient (IQ), executive functions, language and sensorimotor abilities, which can be even worse in patients with mTLE with confirmed hippocampal sclerosis (Hermann et al., 1997; Oyegbile et al., 2004). Nature of frontal lobe dysfunction in TLE is likely to be associated with seizure spread and thus has important clinical implications for prognosis and surgical management (Stretton and Thompson, 2012). A small study suggested that differential impairment of memory tests may help in lateralization of epileptogenic foci, ETLE group performed better than the RTLE group on nonverbal memory measures and better than the LTLE group on verbal memory measures (Breier et al., 1996). The neuropsychological studies on FLE report deficits in motor

coordination and planning, reduced attention span, and difficulties in response inhibition in complex cognitive tasks (Patrikelis et al., 2009). While the localization of many cognitive functions has been clearly described with specific areas of the brain, the localization for functions like memory and language is complex and involves several areas and circuits of the brain (Weber et al., 2006; Binder and Desai, 2011). In addition, while impairment in all important cognitive functions among patients with refractory epilepsy, has been reported in several studies, selective impairment of particular cognitive functions may not necessarily remain localization specific (Weiner et al., 2011). We aimed at testing the hypothesis, hence, that all main cognitive domains of importance to patients suffering from refractory focal epilepsy, viz., memory, language and executive function, are similarly impaired among this patient population, irrespective of localization of the seizure focus and/or lesion. Proving this hypothesis could help neurologists and epileptologists involved in their care, to remain more sensitized to the possibility of more general than specific cognition problems. This would also prove useful in counseling patients during pre-surgical planning. This study was, therefore, conducted to evaluate the prevalence, degree and selectivity of involvement of the domains of memory, language and executive functions among patients with temporal versus extratemporal epilepsy.

Methods This study was conducted at a premier tertiary care hospital of India, over a period of two years, from July 2010 to July 2012. Consecutive adolescent and adult patients with medically refractory focal epilepsy were enrolled prospectively from the neurology services, mainly the intractable epilepsy clinic.

Exclusion criteria Patients excluded were those not giving consent, children below the 12 years, gross mental subnormality (Verbal IQ < 70), patients who could not converse in either Hindi or English languages and patients with any co-morbid neurological or mental illness like autistic disorder, cerebral palsy, severe depression, encephalopathy or any associated speech or hearing impairment. The purpose of the study was explained to the patients and the caregivers and informed consent was taken from the patients or the guardians, in case of minor patients. Ethical clearance had been obtained before initiation of enrollment.

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Definitions

Evaluation of cognition

Epilepsy diagnosis was essentially clinical. Medically refractory epilepsy was defined as the condition which required failure of at least two appropriate antiepileptic drugs (AED) in adequate doses with occurrence of at least one seizure per month for 18 months, and no seizure-free interval longer than three months during that time (Berg, 2006). Temporal lobe epilepsy (TLE) was defined on the basis of clinical seizure semiology of temporal lobe auras (Henkel et al., 2002), automatisms of limbs or orofacial musculature (Jobst et al., 2000), unresponsiveness, limb dystonia and amnesia (Rusu et al., 2005). The history of febrile seizures or other antecedents in early childhood and the characteristic course with initial latent period and stuttering increase in seizure frequency whenever present were used as supportive to this diagnosis and for defining the sub-group of patients with mesial temporal lobe epilepsy (MTLE) (Wieser, 2004). Frontal lobe epilepsy (FLE) was defined based on history of brief seizures, absence of aura, abrupt onset and offset, clustering and predominant occurrence in sleep, with semiology of bizarre proximal automatisms, without postictal symptoms (Ryvlin et al., 2006). Clear limb or facial clonic seizures or seizures with semiology characteristic of supplementary motor area localization, were also categorized under this subgroup (Kotagal et al., 2000). Other extratemporal epilepsies were clinically recognized by characteristic reliable description of somatosensory (Manford et al., 1996) or visual (unformed positive phenomena or negative phenomena) aura (Richer et al., 1991). Based on these definitions and investigational data (MRI brain, video EEG with or without nuclear imaging) for localization of epileptogenic foci, patients were divided into 2 main groups: patients with TLE and those with extratemporal lobe epilepsy (ETLE). The categorization into temporal, frontal, occipital and parietal lobe epilepsy was made by confirming the clinical criteria and presence of either structural (MRI and/or ictal SPECT and/or FDG PET) or neurophysiological (interictal and ictal EEG with ictal semiology) or both, for all patients. The former was further divided into patients with mesial temporal lobe epilepsy with MRI findings of hippocampal sclerosis (MTLE-HS) and those with any other temporal lobe lesion or localization, without hippocampal sclerosis.

After noting personal & relevant clinical details, IQ assessment was carried out to rule out mental retardation. Detailed assessment of language was carried out by VR for all patients using the Western Aphasia Battery, individual subtest scores for spontaneous speech, comprehension, repetition & naming were noted. Aphasia quotient and cortical quotient were calculated using Kertesz formula (Kertesz, 1982) for each patient. Evaluation of memory and executive function was carried out by VR, along with trained psychologists, MA and SP, for all patients included. All three examiners of cognition remained blinded to the clinical, video EEG and MRI details of the patients. The PGI Memory Scale was used for memory assessment (Pershad and Wig, 1976, 1978, 1988). It is a validated battery for memory assessment commonly used in India (Prajapati et al., 2011). PGI memory scale includes 10 subtests including remote memory, recent memory, mental balance (working memory), attention and concentration, immediate recall, delayed recall, verbal retention for similar and dissimilar words, visual retention and recognition. A total score is obtained by adding scores on all subtests (Score range: 0—100). Executive function performance was assessed by using a battery of 4 tests including, trail making test A & B (TMTA, TMT-B) (Tombaugh, 2004), digit symbol test (DST) (Duff et al., 2003), Stroop Task (ST) (Ivnik et al., 1996) and verbal fluency test (VFT) (Tombaugh et al., 1999). Total score of these tests were coded from 0 to 4, using Heaton et al. system of classification of neuropsychological test scores, depending upon lower limit of percentile range of normative data as follows: <1 percentile = 4 (moderate to severe and severe impairment), 1—2 percentile = 3 (moderate impairment), 2—7 percentile = 2 (moderate impairment), 7—16 percentile = 1 (mild impairment) and 16—100 percentile = 0 (normal) (Heaton et al., 2004). Normative data for all tests were available for Indian population, except executive function tests including digit symbol test, Stroop Task and verbal fluency test for which normative data was simultaneously collected by applying this test to 30 normal healthy attendants of patients coming to the neurology clinic.

Localization of epileptogenic focus This was mainly based on semiology of seizures determined by history taking, video EEG and MRI brain. Ictal SPECT & PET scans were used in patients with normal or discordant MRI or as per requirement in individual patients. The clinical details and video EEG data were obtained and analyzed, for all patients, by an experienced epilepsy neurologist (GS). Patient’s personal and demographic details along with complete description of seizures were recorded. Other relevant facts concerning the presence of cognitive impairment and other motor or other deficits were noted.

Statistical analysis All data was tabulated in Microsoft Excel® format and was analyzed through the statistical software SPSS version 16. The statistical analysis was based on basic descriptive statistics. Relative risk (RR) along with 95% confidence interval (CI) was calculated for impairment in all three cognitive domains assessed. Differences between two groups with categorical variables, were calculated through chi-square contingency test and for groups with continuous variables, the independent sample t-test was used for comparing means of variables. Multivariate logistic regression analysis was carried out to identify independent role of localization of epilepsy in impairment in each of the three cognitive domains assessed. A p value of <0.05 was considered significant.

Memory, executive function and language function are similarly impaired in both temporal and extra

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Results

Language performance

We enrolled 102 patients with medically refractory epilepsy prospectively during the study period (July 2010—June 2012). Mean age of patients enrolled was 23.04 ± 8.3 (range 10—47) years. There were 66% (67/102) males and 34% (35/102) females. Mean age of onset of seizures; mean duration of epilepsy and mean seizure frequency were 11 ± 8.2 years, 12.5 ± 7.5 years and 10 ± 13 per month, respectively. Median seizure frequency was 5 (range 1—60) per month. Mean verbal IQ was 83 ± 10. Out of 102 patients, 6 (6%) were illiterate, 36 (35%) educated up to 9th grade, 34 (33%) educated between 10th and 12th class, 21 (20%) were graduates and 5 (5%) had received postgraduate education. Most patients (91%) were right handed. There was no significant difference at baseline between patients with right hemisphere epilepsy focus versus those with left hemisphere focus or those with TLE versus ETLE groups except that the ETLE group patients were younger (mean age 20.8 ± 7.4) than the TLE group (24.6 ± 8.7) (Table 1). Among 102 patients of intractable or drug resistant epilepsy enrolled, 41 patients (40%) had left hemispheric focus and 61 (60%) had right hemispheric focus. TLE was most common, seen in 59 (58%) of patients rest 43 (42%) patients were grouped in ETLE; with 34 patients of frontal lobe epilepsy, 7 patients of parietal lobe epilepsy and 2 patients of occipital lobe epilepsy (Table 2). Among 102 patients of intractable epilepsy 83 (82%) have more than one cognitive domain affected. All three domains were involved in 21 (21%) patients.

Prevalence of language impairment in refractory epilepsy was 47% (48/102). The most common category of aphasia was anomic aphasia, found in 41% of all patients, 1 patient fulfilled criteria for conduction aphasia and one other patient, for trans-cortical sensory aphasia. No significant difference found between various groups compared (TLE Vs ETLE, TLE Vs FLE and TLE-HS Vs other TLE) (Table 5). All aphasia subscores were similar for the ETLE and TLE groups as well as for the FLE subgroup of ETLE, except for the repetition subscore, which was significantly lower in the FLE subgroup (mean score = 86.94 ± 9.4) compared to the TLE group {(91 ± 6.5); p = 0.034} (Table 6). Multivariate analysis adjusting for age of onset, gender, education, seizure frequency, duration of epilepsy showed no significant difference in performance on the memory scale and language assessment, between TLE and ETLE groups {adjusted odds ratio (for memory) = 0.73(0.25—2.06; adjusted odds ratio (for language) = 0.96 (0.34—2.67} (Table 7). Multivariate analysis for the executive function tests could not be done and is meaningless, since all patients showed impairment, majority being severely impaired.

Memory performance Prevalence of memory impairment was 21% with no significant difference between two groups, {TLE (19.7%) and ETLE (23.3%)}. No significant difference found in mean memory scores or severity of memory impairment in various group comparisons including TLE compared to ETLE, TLE compared to FLE and TLE with hippocampal sclerosis (HS) compared to TLE without HS (Table 3).

Executive function performance All patients enrolled in study showed impairment of one or other executive function tests with 93% showing impairment on at least 3 out of 5 tests. All drug refractory epilepsy patients showed impairment on Trail A test with almost 78% showing severe impairment. The performance on this test, was significantly worse for patients with FLE compared to TLE, all patients with ETLE compared to TLE and non HS TLE compared to mTLE-HS (Table 4a). Almost all patients showed impairment on Trail B test (93.2% in TLE, 97.7% in ETLE), with majority showing severe impairment. Though performance was similarly affected in TLE and ETLE group, Trail B performance was significantly poor in FLE and TLE without hippocampal sclerosis when compared with TLE and TLE with hippocampal sclerosis, respectively (Table 4b). Both group showed similar extent of impairment of DST, Stroop task and VFT (Table 4c Table 4d Table 4e).

Discussion This prospective study, conducted with the aim of evaluating the prevalence, degree and selectivity of involvement of the domains of memory, language and executive functions among patients with TLE versus ETLE, revealed significant and similar impairment of all three cognitive domains in both groups. Memory impairment was found to be equally common in both groups, with similar extent of involvement. Severe impairment of all executive functions was observed in majority of patients in both groups, however the ETLE group showed significantly worse performance in the trail making test. Mild language impairment of anomic type was observed in both groups with similar subtest scores except repetition which was more affected in ETLE (mainly FLE) group. Executive function deficit: Prevalence of impairment in more than one cognitive domain, observed in our study is higher (82%) than that reported in previous studies. A retrospective analysis of 65 patients with TLE showed that the majority (78%) of patients with TLE were impaired in more than one cognitive domain, with impaired semantic memory (87%), episodic verbal memory (64%), executive functions (55%) and language (78%) (Wang et al., 2011). We observed impaired executive function in all patients, with impairment in ≥3 tests in 93% patients. Memory and language impairment was observed in 21% and 48%, respectively. Higher prevalence of impaired executive function and in multiple domains in our study could be attributable to the inclusion of both TLE and ETLE patients in whom, stringent intractability criteria were applied and more detailed assessment was carried out by us. Our observation that cognitive impairment in patients with medically refractory TLE is not restricted to memory but includes significant and frequent involvement of executive function and language; is similar to observations in few

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Table 1

Baseline characteristics of patients in the TLE and ETLE groups.

Patient characteristics Age in years* Male (%) Handedness Rt (%) IQ Verbal* Education Illiterate (%) Graduate n above (%) Age of onset in years* Seizure ‘f’ median per month Duration of Epilepsy in years* Left hemisphere (%) *

TLE (n = 59)

ETLE (n = 43)

Significance (p)

24 ± 8 38 (64) 52 (88) 83 ± 10

20 ± 7 29 (67) 41 (95) 81 ± 10

0.024 0.907 0.205 0.357

4 (7) 17 (29)

2 (5) 9 (21)

0.774 0.774

12 ± 8 4 (1—50) 13 ± 7 24 (41)

9.7 ± 8 5 (1—60) 12 ± 7 17 (39.5)

0.071 0.451 0.750

Values expressed in mean ± standard deviation

Table 2

Basis of localization of epileptogenic foci in our patients.

Localization

Clinical + VEEG + MRI or nuclear imaging (n)

Clinical + VEEG (n)

Clinical + MRI or nuclear imaging (n)

Temporal (n = 59) Frontal (n = 34) Parietal (n = 4) Occipital (n = 1)

49 29 4 2

3 2 — —

7 3 3 1

Table 3

Comparison of memory performance among various study groups. Memory score mean (SD)

TLE ETLE p Value TLE FLE p Value TLE-HS Other TLE p Value

Table 4a

70.4 ± 15.0 68.1 ± 13.5 0.44 70.4 ± 15.0 68.1 ± 14.0 0.47 71.1 ± 15.0 68.7 ± 15.3 0.54

p Value

Normal

Mild

Mild to mod

Mod

Severe

48 (81.3) 33 (76.7)

3 (5.1) 3 (6.9)

1 (1.7) 3 (6.9)

2 (3.4) 1 (2.3)

5 (8.5) 3 (6.9)

0.96

48 (81.4) 26 (76.5)

3 (5.0) 2 (5.9)

1 (1.7) 3 (8.8)

2 (3.4) 1 (2.9)

5 (8.5) 2 (5.9)

0.83

30 (85.7) 19 (76.0)

1 (2.9) 2 (8.0)

0 (0.0) 1 (4.0)

1 (2.9) 1 (4.0)

3 (8.6) 2 (8.0)

0.58

Comparison of Trail A performance among various study groups. Trail A score median (range)

TLE ETLE p Value TLE FLE p Value TLE-HS Other TLE p Value

Severity of impairment [n (% of subjects)]

68 (31—502) 86 (32—282) 0.009 68 (31—502) 84 (44—282) 0.014 58 (31—400) 80 (40—502) 0.041

Severity of impairment [n (% of subjects)]

p Value

Normal

Mild

Mild to mod

Mod

Severe

0 (0) 0 (0)

4 (6.8) 0 (0)

9 (15.2) 3 (6.9)

6(10.2) 3 (6.9)

40 (67.8) 37 (86.0)

0.02

0 (0) 0 (0)

4 (6.8) 0(0)

9(15.2) 1(2.9)

6(10.2) 3(8.8)

40 (67.8) 30(88.2)

0.93

0 (0) 0 (0)

3(8.6) 1(4.0)

7(20%) 2(8%)

5 (14.3) 20(57.1) 1(4.0) 21(84.0)

0.73

Memory, executive function and language function are similarly impaired in both temporal and extra Table 4b

Comparison of Trail B performance among various study groups. Trail A score median (range)

TLE ETLE p Value TLE FLE p Value TLE HS Other TLE p Value

Table 4c

154.5 (56—596) 178 (50—539) 0.22 154.5 (56—596) 178 (65—539) 0.42 120.5 (59—596) 174 (56—304) 0.44

Severity of impairment [n (% of subjects)] Normal

Mild

Mild to mod

Mod

Severe

4 (6.8) 1 (2.3)

1 (1.7) 1 (2.3)

4 (6.8) 2 (4.6)

4 (6.8) 4 (9.3)

46(77.9) 35(81.4)

0.45

4 (6.8) 0 (0)

1 (1.7) 1(2.9)

4 (6.8) 2(5.9)

4 (6.8) 4(11.8)

46(77.9) 27(79.4)

0.05

1(2.9) 3(12)

0 (0) 1(4)

4(11.4) 0 (0)

3(8.6) 1(4.0)

27(77.1) 20(80.0)

0.04

27 (0—65) 25 (0—56) 0.64 27 (0—65) 25 (0—54) 0.64 28 (0—65) 25 (0—65) 0.26

Severity of impairment [n (% of subjects)] Mild

Mild to mod

Mod

Sever

16 (27.1) 14 (32.5)

9(15.2) 5(11.6)

7(11.9) 0 (0)

1 (1.7) 0 (0)

26(44.0) 24(55.8)

0.45

16(27.1) 11(32.2)

9(15.2) 4(11.8)

7(11.9) 0(0%)

1 (1.7) 0(0%)

26(44.1) 19(55.9)

0.30

11(31.4) 5(20.0)

7(20.0) 2(8.0)

3(8.6) 4(16.6)

1(2.9) 0(0)

13(37.1) 14(56.0)

0.55

performance of patients with FLE on memory tasks (Weiner et al., 2011). Memory deficits: Findings resembling our observation of prevalent memory deficits in both TLE and ETLE groups have been reported previously. Weiner et al. (2011) tested the hypothesis that patients with TLE would demonstrate relatively more impairment on a test of everyday memory, while patients with FLE would demonstrate relatively more

Comparison of Stroop test performance (CW) among various study groups. CW score median (range)

TLE ETLE p Value TLE FLE p Value TLE HS Other TLE p Value

p Value

Normal

previously published studies (Helmstaedter and Lendt, 2001; Oyegbile et al., 2004; Hermann et al., 2008). In ETLE, cognitive deficits usually found are more diffuse than in TLE, particularly in childhood (Helmstaedter et al., 1996). The most common deficits reported in FLE are in attention, planning and executive functions (Boucsein et al., 2002; Hernandez et al., 2003; Upton and Thompson, 1996) while other studies report significantly poor

Table 4d

p Value

Comparison of DST performance among various study groups. DST score median (range)

TLE ETLE p Value TLE FLE p Value TLE HS Other HS p Value

77

23 (0—48) 22 (0—65) 0.61 23 (0—48) 22.5 (0.65) 0.71 24 (0—48) 22 (0—48) 0.48

Severity of impairment [n (% of subjects)]

p Value

Normal

Mild

Mild to mod

Mod

4 (Severe)

45 (76.3) 30 (69.8)

8(13.6) 6(13.9)

0 (0) 2(4.6)

0 (0) 0 (0)

6(10.2) 5(11.6)

0.73

45 (76.3) 24(70.6)

8(13.6) 4(11.7)

0 (0) 2(5.9)

0 (0) 0(0)

6(10.2) 4(11.7)

0.65

26(74.3) 19(76.0)

5(14.29) 0 (0) 4(16%) 0 (0)

0 (0) 0 (0)

4(11.4) 2(8.0)

0.11

78 Table 4e

V.K. Rai et al. Comparison of VFT performance among various study groups. VFT score median (range)

TLE ETLE p Value TLE FLE p Value TLE HS Other TLE p Value

Table 5

Severity of impairment [n (% of subjects)]

14 (0—40) 12 (0—35) 0.80 14 (0—40) 12 (0—30) 0.52 13 (0—40) 14 (4—34) 0.98

Normal

Mild

Mild to mod

Mod

4 (6.8) 1 (2.3)

3(5.1) 7(16.3)

33(55.9) 23(53.5)

18(30.5) 1(1.7) 10(23.3) 2 (4.6)

0.59

4 (6.8) 0(0)

3(5.1) 5(14.7)

33(55.9) 19(55.9)

18(30.5) 1(1.7) 8(23.5) 2(5.9)

0.49

3(8.6) 1(4.0)

2(5.7) 1(4.0)

17(48.6) 17(68.0)

12(34.3) 1(2.9) 6(24) 0(0)

0.78

92.05 ± 8.09 91.30 ± 6.76 0.62 92.05 ± 8.09 90.91 ± 7.08 0.49 91.48 ± 9.97 92.84 ± 4.02 0.52

TLE ETLE p Value TLE FLE p Value TLE HS Other TLE p Value

Impairment [n (% of subjects)] Normal

Impaired

33 (52.9) 21(48.8) 0.478 33 (55.9) 16 (47.1) 0.409 20 (57.1) 13 (52.0) 0.693

26 (44.1) 22 (51.2) 26 (44.1) 18 (52.9) 15 (42.9) 12 (48.0)

Mean scores of language performance in patients with TLE v/s ETLE.

Language performance

TLE (n = 59)

Spontaneous speech Comprehension Repetition Naming Aphasia quotient

18.5 190 91 88 93.4

± ± ± ± ±

1.2 20 6.5 7.6 5

impairment on a test of everyday executive function. However, both groups were found to have significantly impaired daily memory functioning, while their executive daily functioning test scores were within normal limits, suggesting that

Table 7

Severe

Comparison of language performance among various study groups. Aphasia quotient (mean ± SD)

Table 6

p Value

ETLE (n = 43) 18.3 192 87.6 87 92.7

± ± ± ± ±

1.4 10 8.6 7 4.8

Significance (p value) 0.338 0.699 0.028 0.481 0.487

despite having focal lesions, functional impairments could be seen in a broad range of daily activities. Small sample size with a wide difference in the number of patients in the two groups (TLE = 25, FLE = 9), inclusion of patients

Multivariate analysis adjusting for age of onset of epilepsy, seizure frequency, epilepsy duration, gender and education.

ETLE [n = 43 (%)] TLE [n = 59 (%)] p Value Unadjusted odds ratio (95% confidence interval) Adjusted odds ratio* (95% confidence interval)

Impaired memory

Impaired language

10 (23.3) 11 (18.6) 0.57 0.76 (0.29—1.98) 0.73 (0.25—2.06)

22 (51.2) 26 (44.1) 0.48 0.75 (0.34—1.65) 0.96 (0.34—2.67)

Reference category: ETLE. * Adjusted for age of onset of epilepsy, seizure frequency, epilepsy duration, gender and education.

Memory, executive function and language function are similarly impaired in both temporal and extra with epilepsy controlled with medications, and use of everyday executive function tasks (less sensitive test) may have lead to this reported underestimation of executive function impairment. Our finding of similar involvement of semantic memory in both ETLE and TLE groups is in agreement with the observations of Drane et al. (2006), in a prospective study of 29 patients (FLE 9, TLE 20), that semantic fluency (animal naming) is impaired in both FLE (78%) and TLE (35%) regardless of the laterality of seizure onset. These findings may suggest that the semantic fluency test is a complex cognitive task encompassing aspects of language functioning, executive control processes, attention, and semantic memory. Language deficits: In our study there was no significant difference in subtests of language assessment between two sides except repetition impairment in FLE compared to the TLE group. Another study of language function in 23 intractable TLE patients (left 12, right 11) made similar observations, reporting impairment in a total of 7 patients (30%), with no significant differences in total scores or sub scores among patients with left TLE versus right TLE, except in spontaneous speech, which was more impaired in left TLE (Bartha et al., 2005).

Limitations The main limitation of our study was not comparing cognitive function with matched normal controls. However, normative data used in this study had been systematically collected prior to initiation of the study and Indian normative data were used.

Conclusion On comprehensive evaluation, cognitive impairment in either of all of the three domains of memory, language and executive function is very common among patients with medically refractory epilepsy. Contrary to popular belief, this impairment is generally similar among patients with TLE as compared with those having ETLE, except that of impaired trail making test performance among patients with ETLE.

Conflict of interest statement None of the authors has any conflict of interest to disclose.

Acknowledgements The authors wish to acknowledge the constant assistance obtained from Dr. Anupama Gupta and Ms. Jyoti Katoch in data collection and analysis, during this study as well as the help obtained from Dr. M Kalaivani in the statistical analysis.

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