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July2011 Vol.48 Issue:      3 (Supp.) Table of Contents
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Cognitive Impairment in Patients with Unilateral Temporal Lobe Epilepsy

M. Ashraf M. Zaitoun1, Ahmed D. Al Anwar1, Alaa A.M. Abdel Ghani1,

Khaled A. M. El-Sharkawy1, Wafaa S. Hassan1, Ahmed O. Abu Al Ezz2

 

Departments of Neurology1, Radiology2, Zagazig University; Egypt

 



ABSTRACT

Background: Neuropsychological impairment is an important co-morbidity of epilepsy. Objective: Study of cognitive functions and their relationship with a number of clinical parameters and MRI brain findings in patients with unilateral temporal lobe epilepsy (TLE). Methods: The present study was carried out on 50 patients with unilateral TLE, with a mean age of 31.22±9.22 years and 10 healthy controls. All patients and controls were subjected to neuropsychological assessment, interictal EEG and MRI study of the brain. Results: The patients performed worse than controls in the neuropsychological evaluation. There was a negative statistical correlation between immediate recall, language, visuoconstructive and executive functions and the duration of illness, and a positive statistical correlation between cognitive functions results and educational status of patients in verbal memory, language, and executive functions. There was significant impairment in patients under polytherapy in comparison to the others in delayed recall, visual memory, visuoconstructive and executive function. Patients with secondary generalization EEG discharge were found to be significantly impaired in delayed recall, visual memory and visuoconstructive function. Those with abnormal MRI findings were found to be impaired in delayed recall, visuoconstructive and executive function. Among left TLE patients with abnormal MRI study, patients with hippocampal sclerosis (HS) were found to be impaired in verbal memory, language, and executive functions, while patients with right TLE who had HS were found to be impaired in visual memory. Conclusion: Cognitive deficits in patients with TLE extend beyond memory deficits, so that psychological interventions should to be made routinely as part of the overall management plan of TLE. [Egypt J Neurol Psychiat Neurosurg.  2011; 48(3): 247-256]

 

Key Words: Cognitive, Temporal lobe, Epilepsy.

 

Correspondence to Alaa Abdel Ghani, Neurology Department, Zagazig University, Egypt,

Tel.:+20123006744       Email: alaa_abdelghani@hotmail.com.




 


INTRODUCTION

              

Temporal lobe epilepsy (TLE) is the most frequent partial epilepsy in adults and the most common type of medically refractory epilepsy amenable to surgical treatment in this age group. The selection of these patients for surgery depends on the concordance of clinical, electroencephalographic (EEG) and magnetic resonance imaging (MRI) findings1,2.

Cognitive decline has long been recognized as a consequence of TLE. The most prominent cognitive deficit occurs in memory function, this is due to the effect of the primary epileptogenic lesion3,4. However, it has become apparent that cognitive impairment may be evident in other cognitive domains, abnormalities that can not be explained by the primary TL disturbance5,6. Seizure-related contributors to cognitive impairment in TLE include the underling pathology of the disorder, seizure frequency and severity, duration of epilepsy, adverse effects of medications, medical complications such as status epilepticus, inter ictal epileptiform discharges and alterations in brain metabolism7-10.

Hippocampal sclerosis (HS) is the most common pathologic findings in adult patients with TLE. The features of HS identified by MRI are hippocampal atrophy, demonstrated with coronal T1-weighted images, and increased signal intensity within the hippocampus on T2-weighted spin-echo images11,12.

The aim of this study was to examine cognitive functions in a sample of patients with unilateral temporal lobe epilepsy and to correlate the neuropsychological data with a number of clinical parameters and MRI findings.

 

SUBJECTS AND METHODS

 

This study was carried out at Neurology Department, Zagazig University Hospitals.

 

Subjects

Research participants (N=60) included 50 right handed patients with unilateral TLE and 10 healthy control subjects. Selection criteria for epileptic patients included: (1) chronological age from18 to 49 years (2) partial seizures of TL origin based on clinical semiology, clinical history and interictal EEG, according the guidelines of the international League against Epilepsy13, (3) seizures of unilateral TL origin as shown by clinical semiology and/or interictal EEG and/or unilateral lesions within the temporal lobes by MRI findings. Exclusion criteria included: 1-Left handed patients as subjects with right hemisphere language dominance show less lateralized hemispheric specialization for memory processing14. 2- Neuropsychiatric or systemic disorders which may affect cognitive functions and drug abuse seizures.

The healthy control right-handed subjects were matched to the patients with respect to age, gender, socioeconomic state, and educational level.

 

All patients and controls were subjected to the following:

1-      Full history taking according to epilepsy sheet which is consistent with current guidelines of the international league against epilepsy.

2-      Complete physical and neurological history and examination.

3-      Routine laboratory investigations: complete blood picture, erythrocyte sedimentation rate (ESR), blood glucose level, serum electrolytes, liver and kidney functions.

4-      Interictal Electroencephalography (EEG): Electroencephalography was done for all patients using 32 channels digital EEG Nicolet Biomedical, Alliance Works. Electrodes were arranged according to the international 10-20 system of surface electrode placement using mono and bipolar montages. Hyperventilation for three minutes together with intermittent photic stimulation used as a provocation methods for all patients. The EEGs tracing was analyzed as regards: background activity, generalized slowing or spike and wave, focal slowing or spike and wave and focal with secondary generalization.

5-      Magnetic Resonance Imaging (MRI) of the brain: All patients underwent 0.5 Tesla (GE) equipment with T1 and T2 weighted images in the axial, coronal and sagittal planes. Hippocampus sclerosis (HS) is best depicted by using thin coronal sections that are angled perpendicularly to the hippocampus with T1 and T2 weighted images and fluid attenuated inversion recovery (FLAIR) sequences. HS was diagnosed on the basis of evidence of hippocampal atrophy on T1 slices and/ or increased signal intensity in the hippocampus on T2 and/ or  FLAIR weighted images or both by visual inspection11,12.

6-      Neuropsychological Assessment: Patients and control subjects were administered a comprehensive test battery that included Verbal Memory: immediate and delayed recall (Rey Auditory Verbal Learning (RAVL) test15 and digit Span(a subtest of the Wechsler Adult Intelligence Scale-Revised)16); Visual Memory(Benton Visual Retention Test (BVRT))17; Language( Controlled Oral Word Association (COWA) test)18; Visuo-Constructive Function (Block design, a subtest of WAIS-R)16 and Executive Function(Trail making test (B) time complete)19.

 

Statistical Analysis

All results were collected and analyzed statistically using Statistical Package for Social Sciences (SPSS) for windows version13.0. Student's t-test was used to test the probability, one way ANOVA (Analysis of Variance) test to compare more than two groups as regards quantitative variables and spearman correlation coefficient was used to determine positive or negative correlation between variables. P-values less than or equal to 0.05 were considered as statistically significant.

 

RESULTS

 

The age of the patients  ranged between 18 and 49 years with a mean age of 31.22±9.22 years, they were 28 males (56%) and 22 females (44%), the mean duration of educational years was 10.4±4.57. Control subjects did not differ from patients with respect to age, gender and educational level. 22(44%) of the patients had left TLE and 28(56%) had right TLE. According to the international classification of seizures in 1981, 17(34%) of the patients had partial seizures and 33(66%) had partial with secondary generalization seizures. The duration of illness in patients ranged from 4 months to 360 months with a median 54 months. Seizure frequency ranged from 7 per day to 2 per year. As regards antiepileptic drugs (AEDs), 15(30%) of the patients received polytherapy, 33(66%) monotherapy and 2(4%) did not receive AEDs. EEG was normal in 10(20%) of the patients and abnormal in 40 (80%) (Focal discharges in 23 and focal with secondary generalization in17 patients). MRI study of the brain was normal in 22(44%) of the patients and abnormal in 28(56%) (HS (9), tumor (4), cyst (4), calcification (3), infarction (3), and encephalomalacia (5).

               Regarding  cognitive functions tests, the patients′ group was found to be significantly impaired in all cognitive domains in comparison to the controls' group (P<0.05) (Table 1). Among the patients′ group, those with left TLE were found to be impaired in verbal memory and language function while those with  right TLE were found to be impaired in visual memory (Table 2). The presence of MRI abnormalities was associated with significant higher mean of age and longer duration of illness than patients with normal MRI ,while patients with HS had significant higher mean of age, longer duration of illness and earlier age of seizure onset than patients with normal MRI or other MRI abnormalities (Table 3). There was a negative statistical correlation between immediate recall, language, visuoconstructive and executive function and the duration of illness(Table 4), while a positive statistical correlation was found between cognitive functions results and educational status of patients in verbal memory, language, and executive functions reaching a significant level in only digit span and language domains (Table 5). There was significant impairment in patients under polytherapy in comparison to those with monotherapy and those not receiving AEDs in delayed recall , visual memory, visuoconstructive and executive functions (Table 6). Patients with secondary generalized discharge in EEG were significantly impaired in verbal memory (delayed recall), visual memory and visuoconstructive functions in comparison with patients with normal EEG or focal discharge (P<0.05) (Table 7).

               Patients with abnormal MRI were found to have lower mean scores than patients with normal MRI across all cognitive domains and higher mean scores in executive functions. These results were not statistically significant except in delayed recall, visuoconstructive and executive functions (Table 8). Among left TLE patients with abnormal MRI study, those with HS were found to be impaired in verbal memory (immediate recall,), language, and executive function (Table 9). On the other hand, patients  with right TLE who have  HS were found to be impaired in visual memory (Table 10).


 

Table 1. Comparison of cognitive functions results between patients and controls.

 

Cognitive domains

Patients (n=50)

Controls (n=10)

P

M

SD

M

SD

Verbal memory

Immediate recall

21.5

10.12

28.2

4.21

0.045*

Delayed recall

11.3

5.8

15.6

2.32

0.025*

Digital span

7.08

3.02

9.8

1.99

0.009**

Visual memory

3.74

2.13

5.6

1.89

0.013*

Language function

20.38

7.87

26.1

3.07

0.028*

Visuoconstructive function

4.96

3.33

8.4

1.26

0.002**

Executive function

59.44

13.68

50

6.2

0.038*

M mean, SD standard deviation              

* Significant at p<0.05, ** Significant at p<0.01

 

Table 2. Comparison of cognitive functions results in right and left temporal lobe epilepsy patients.

 

Cognitive domains

Right TLE (n=28)

Left TLE (n=22)

P

M

SD

M

SD

Verbal memory

Immediate recall

27.79

8.56

13.5

5.02

0.000*

Delayed recall

15.86

3.19

5.5

1.59

0.000*

Digit span

8.90

2.35

4.77

2.07

0.000*

Visual memory

2.32

0.77

5.55

1.92

0.000*

Language function

25.07

6.47

14.41

4.91

0.000*

Visuoconstructive function

5.00

3.40

4.91

3.31

0.925

Executive function

61.43

13.09

56.91

14.29

0.250

M mean, SD standard deviation, TLE temporal lobe epilepsy

* Significant at p<0.01

 

Table 3. Demographic data of temporal lobe epilepsy patients with normal and abnormal magnetic resonance imaging (MRI).

 

 

Normal MRI

Abnormal MRI

P value

HS

Other MRI abnormalities

P1

P2

P3

Number

22

9

19

 

 

 

Age, y (M±SD)

26±6.8

36.1±7.5

34.9±9.6

<0.001*

<0.001*

>0.05

Sex ratio M:F

11:11

3:6

8:11

0.68

Age of seizure onset, y  (M±SD)

25.1±6.8

14.8±7.7

25.5±10.2

<0.001*

>0.05

<0.001*

Duration, y Median    

0.75

20.0

7.0

<0.001*

<0.001*

<0.001*

Range                       

0.4 – 4

15 – 30

3 – 30

P1: Normal MRI Vs HS.

P2: Normal MRI Vs other MRI abnormalities.

P3: HS and other MRI abnormalities.

HS hippocampal sclerosis, M mean, SD standard deviation                                 

* Significant at p<0.01

Table 4. Correlation between cognitive functions results and TLE duration.

 

Cognitive functions

R

P

Verbal memory

Immediate recall

-0.391

0.005*

Delayed recall

0.007

0.96

Digit span

-0.047

0.75

Visual memory

0.022

0.877

Language function

-0.402

0.003*

Visuoconstructive function

-0.391

0.005*

Executive function

-0.502

0.000*

* significant at p<0.01

 

 

Table 5. Correlation between cognitive function results and educational status of the patients.

 

Cognitive functions

R

P

Verbal memory

Immediate recall

+ 0.26

0.06

Delayed recall

+ 0.19

0.17

Digit span

+ 0.36

0.010*

Visual memory

0.18

0.20

Language function

+ 0.34

0.016*

Visuoconstructive function

0.14

0.33

Executive function

+ 0.09

0.52

* Significant at p<0.05

 

 

Table 6. The relation between cognitive functions results and pattern of medications.

 

Cognitive functions

No treatment

Monotherapy

Polytherapy

ANOVA

M

SD

M

SD

M

SD

F

P

Verbal memory

Immediate recall

23.2

13.07

20.85

8.95

19.50

0.71

0.310

0.735

Delayed recall

11.6

6.82

11.52

5.39

5.50

0.71

3.043

0.030*

Digit span

7.21

2.87

6.00

2.83

6.93

3.51

0.171

0.848

Visual memory

7.5

2.12

4.07

2.66

3.36

1.17

4.340

0.019*

Language function

20.85

6.83

19.93

10.34

16.00

0.01

0.382

0.685

Visuoconstructive function

8.00

5.66

5.91

3.00

2.47

2.39

8.301

0.001**

Executive function

50.93

11.58

63.03

12.85

64.00

21.21

4.793

0.013*

* Significant at p<0.05 ** Significant at p<0.01

 

Table 7. The effect of various EEG changes on the results of cognitive functions.

 

Cognitive functions

Normal EEG

n=10

Focal discharge

n=23

Focal with 2ry       generalization

n=17

ANOVA

M

SD

M

SD

M

SD

F

P

Verbal memory

Immediate recall

24.8

10.25

22.17

10.17

18.65

9.83

1.271

0.290

Delayed recall

16.48

6.47

9.80

4.89

7.41

5.11

3.436

0.044*

Digit span

7.7

2.49

7.52

3.45

6.12

2.57

1.336

0.273

Visual memory

6.71

2.28

3.50

1.74

2.13

1.27

3.986

0.030*

Language function

21.6

6.83

21.43

8.97

18.23

6.73

0.955

0.392

Visuoconstructive function

8.00

3.30

4.04

2.70

2.82

1.96

4.793

0.013*

Executive function

57.29

15.43

62.00

11.31

59.91

13.57

0.388

0.680

M mean, SD standard deviation              

* Significant at p<0.05

Table 8. Cognitive functions results in relation to MRI findings.

 

Cognitive functions

MRI

t-test

Normal (n=22)

Abnormal (n=28)

M

SD

M

SD

P

Verbal memory

Immediate recall

21.82

11.72

21.09

7.88

0.803

Delayed recall

12.41

4.21

10.21

6.88

0.009**

Digit span

7.55

2.61

6.71

3.30

0.340

Visual memory

3.85

2.25

3.59

1.99

0.665

Language function

20.68

5.74

20.14

9.31

0.813

Visuoconstructive function

6.45

3.34

3.78

2.84

0.004**

Executive function

55.82

14.61

64.04

11.04

0.033*

M mean, SD standard deviation              

* Significant at p<0.05, ** Significant at p<0.01

 

Table 9. The effect of abnormal MRI (hippocampal sclerosis versus other abnormalities) on the cognitive function results among left TLE patients.

 

Cognitive functions

Left TLE with abnormal MRI (n=15)

t-test

Hippocampal sclerosis (n=5)

Other abnormalities (n=10)

M

SD

M

SD

P

Verbal memory

Immediate recall

8.00

1.41

14.50

3.83

0.003**

Delayed recall

3.20

1.09

6.90

1.72

0.051*

Digit span

3.00

0.70

4.90

2.13

0.079

Visual memory

6.80

2.28

4.70

1.49

0.060

Language function

9.20

6.09

15.80

3.82

0.022*

Visuoconstructive function

2.80

1.92

4.80

3.15

0.220

Executive function

75.41

7.02

53.61

13.28

0.001**

M mean, SD standard deviation              

* Significant at p<0.05, ** Significant at p<0.01

 

Table 10. The effect of abnormal MRI (hippocampal sclerosis versus other abnormalities) on the cognitive function results among right TLE patients.

 

Cognitive functions

Right TLE with abnormal MRI (n=13)

t-test

Hippocampal sclerosis

(n=4)

Other abnormalities

(n=9)

M

SD

M

SD

P

Verbal memory

Immediate recall

35.25

9.60

31.66

5.12

0.389

Delayed recall

19.50

2.38

17.88

2.89

0.062

Digital span

9.55

0.88

10.75

2.06

0.093

Visual memory

0.75

0.50

3.22

0.66

0.050*

Language function

30.50

6.45

28.11

5.15

0.071

Visuoconstructive function

3.75

1.50

3.22

3.34

0.772

Executive function

63.98

4.08

63.16

14.56

0.101

M mean, SD standard deviation              

* Significant at p<0.05

 

 


DISCUSSION

              

Over the past decade, various studies have been carried out to characterize cognitive dysfunction in patients with TLE. In these patients cognitive dysfunction extends beyond memory function, compromising other cognitive such as executive function, language, motor speed and measures of intelligence5,20. A number of factors seem to correlate with cognitive decline in refractory TLE including underlying pathology, seizure frequency, duration of epilepsy, seizure medications, interictal epileptiform discharges and alteration of brain metabolism7-10.

               In our study, we were able to identify significant cognitive impairment extending beyond specific memory deficits. When compared with healthy control subjects, our patients had deficits that included language, executive function and visuoconstructive, as well as memory itself. These findings are in agreement with prior results: In a cross- sectional study of (5) patients with TLE exhibited not only worse memory function but worse performance across measures of intelligence, language, executive function and motor speed. Hermann et al.2, identified a subset of patients with chronic TLE who had cognitive decline in the domains of confrontational naming, delayed visual memory, delayed verbal memory and motor speed and in the series of Marques et al.21, the patients with TLE when compared with control subjects, had deficits, that included language, executive functions, spatial organization and memory.

As regard comparison between left TLE and right TLE patients on cognitive domains measures, we found that left TLE patients had impaired verbal memory and language, while right TLE patients showed impaired visual memory. No difference was found between the two groups in other parameters. These results are in agreement with Barr et al.22, who found that right TLE patients obtained lower mean scores on visual memory than left TLE patients, with preserved verbal memory and language skills among those patients23 collected  neuropsychological data of 44 TLE patients, and found that left TLE patients had significantly lower mean scores in verbal memory and language domains than right TLE patients. Billingsley et al.24 stated impaired verbal memory in patients with either left or right TLE focus. It has been suggested that association between verbal memory and left temporal lobe, and the difficulties in documenting the association between visual memory and right temporal lobe, reflecting the inadequacies of the traditional memory tests, as many of the visual tests can be coded both verbally and visually. This may affect the more variable results of visual memory25,4.

               The relationship between neuropsychological test scores and duration of epilepsy was extensively explored. Jokeit and Ebner7 studied 209 patients with unilateral TLE correlating duration of epilepsy with cognitive decline and obtained convincing evidence that the cognitive abilities of these patients deteriorate with increasing duration of intractable epilepsy. Hermann et al.26 study demonstrated a significantly lower cognitive function in patients with TLE of childhood onset compared with onset in early adulthood. Oyegbile et al.5 found that, the degree of cognitive morbidity per patient to be significantly associated with the duration of epilepsy in their 96 patients with chronic TLE. Marques et al.21 showed a correlation between the duration of epilepsy ranged from 9 to 56 years and the degree of cognitive impairment. Longer duration of epilepsy correlated with an increased number of measures outside the normal limits. Also Kaaden and Helmstaedter6 results clearly demonstrated that patients with TLE with early onset performed more poorly in neuropsychological tests than those with later onset. Our results were compatible with these previous studies as we found a negative correlation between immediate recall, language, visuoconstructive, executive functions and the duration of epilepsy. Experimental studies in chronic rodent models of epilepsy have shown that kindled seizures induce progressive cellular alterations and neuronal loss, increasing the susceptibility to evoked and spontaneous seizures and importantly, behavioral and cognitive deficits that worsen as a function of the cumulative number of seizures27. One might reasonably anticipate a similar relationship in humans, with increasing years of intractable epilepsy resulting in progressive cognitive impairment5. However, it has proven surprisingly difficult to document this relationship8,28.

It should be remembered that the duration of epilepsy is a composite factor that probably reflects the influence of several factors (cumulative impact of seizures, AEDs, pathological interictal brain activity, etc.) acting alone or more likely in combination, the relative explanatory power of each remaining to be clarified. The longer one suffers from intractable epilepsy, the higher the possibility of exposure to factors that result in seizure-induced neuronal damage5,3,6.

               Our study demonstrated positive correlation between all measured cognitive domains (except visual memory and visuoconstructive) and educational status of patients reaching a significant level in digit span  and language domain. Higher educational level may protect against cognitive decline in neurological diseases. This has been well established in patients with Alzheimer disease, in whom higher education seems to diminish the rate of progression of memory loss and other cognitive impairments. This property has been called cerebral reserve in these patients5. The hypothesis of cerebral reserve is not definite in epilepsy patients7,5,21. Jokeit and Ebner7 observed that better educated persons in the successively longer seizure duration group diminished intellectually as much as did the less educated group, but perhaps not as rapidly. Oyegbile et al.5 tested this hypothesis in 96 patients with TLE and found that for those with more years of formal schooling correlation between the duration of epilepsy and cognitive decline was different from the data for patients with fewer years of education. Lower educational level is an indication of low cerebral reserve which means that the patients with more education have greater capacity to withstand the neurobiological insult, because they have increased cognitive reserve. In a study on  64 epileptic  patients, including 31 with high educational level and 33 with low  educational level, Pai and Tsai29 found that patients with high educational level have better cognitive functioning than those with low educational level after epilepsy has developed, which supports the cognitive reserve theory. However, in Marques et al.21 study, this association was not confirmed. This could be the consequence of psychosocial difficulties, characteristic of their population, who were from low educational and socioeconomic levels. 

               Regarding the effect of seizure type on cognition, our study showed that  patients with secondarily generalized seizures were found to have lower mean scores across the measured cognitive domains than patients without secondary generalization, which was non-significant. These findings are concomitant with that of Loiseau et al.30 and Dodrill8, who reported an effect of seizures generalization on general intellectual ability. On the other hand, Kramer et al.28 did not find a relationship between secondarily generalized seizures and cognition.

We also observed that patients with generalized EEG discharges were significantly impaired in verbal memory (delayed recall), visual memory and visuoconstructive function. This is in accordance with Aldenkamp(31), Holmes et al.9 and Mantoan et al.10,who reported that interictal epileptiform discharges (IEDs) have been associated with cognitive impairment.

               Antiepileptic drugs (AEDs) are more likely to have adverse cognitive effects at higher doses, higher blood levels or rapid upward titration. In addition, taking several different AEDs has an additive effect, increasing toxicity. There are differences in adverse cognitive effects between AEDs and individual patients differ in susceptibility to and metabolism of AEDs32. In our work, we found that patients who were under polytherapy performed poorer in delayed recall memory, visual memory, visuo-constructive and executive function. Polytherapy produced greater cognitive impairment. A review of studies employing polytherapy versus monotherapy or tapering from polytherapy to monotherapy suggested a significant deleterious effect of polytherapy across most studies33,34.

               MRI is a sensitive method for detection of HS. Volumetric data may aid in the diagnosis of this condition12. Oyegbile et al.5 have reported an association of cognitive deficits with small hippocampal volume as well as with reduced total brain volume. Therefore hippocampal atrophy may be a marker for cognitive impairment as well as a predictor of cognitive decline. In our study, we found that patients with HS had a statistically significant higher mean age of patients, longer duration of illness and earlier age of seizure onset than patients with normal MRI or other MRI abnormalities. These findings agree wholly or in part with prior studies. Several authors have found that longer duration of epilepsy, earlier age at onset or both to be related to diminished hippocampal volume, prolonged T2 relaxation times, reduced NAA/Cr or increased severity of HS on pathological evaluation35,36,37,21,10. Many animal studies have demonstrated that seizures can produce progressive neuronal loss in the hippocampus38,27. Taken together, these studies suggest that HS may be a progressive disorder with risk of cognitive dysfunction. The hippocampus is a critical structure for anterograde declarative memory, however the mechanisms underlying encoding, reinforcement and retrieval of memory are not well understood39. Patients with chronic TLE demonstrated deficit in verbal and non- verbal memory that correlate with decreased neuronal attenuation within the hippocampi and hippocampal atrophy35,40. Studies using MR imaging- based volume measurement confirm this relationship. Also, volumetric abnormalities have been reported in extrahippocampal mesial TL, temporal neocortex and extratemporal regions11,12. In particular, abnormalities of the left hippocampus have been correlated with verbal memory deficits and abnormalities of the right hippocampus with visuo spatial memory in addition, abnormalities in baseline volumetric measurements of other regions of interest were predictive of adverse changes in other cognitive abilities23,37,39,34.

In our population of patients with TLE, we found that left TLE patients, in whom HS were detected in their MRIs, are impaired in verbal memory, language and executive functions assessment, while right TLE patients, who had detected HS in their MRIs ,are impaired in visual memory assessment. These results are in agreement with that of Barr et al.41, who demonstrated a correlation between verbal memory scores and left hippocampal volume and between visual memory scores and right hippocampal volume measurements before surgery. Hermann et al.42 stated that patients with left HS  performed significantly worse than left TLE patients without HS on verbal memory  and on language function. Their right TLE patients who had HS performed significantly worse than others who were without HS, on visual memory. Lui et al.39 found abnormalities of left hippocampal mean diffusivity to be negatively correlated not only with verbal memory tests but also with visuospatial memory tests. Similarly, right hippocampal diffusivity demonstrated negative correlation with non verbal memory test and visuo- spatial test. These findings suggested that verbal and non verbal memory are incompletely lateralized. Patients of Messas et al.34 with left HS showed impaired performance in tests measuring verbal memory. Right HS may also negatively influence memory performance, though to a lesser extent, than in patients with left HS.

               In conclusion, our findings indicated that: (1) MRI abnormalities including HS are associated with higher mean age of patients, longer duration of epilepsy and earlier age of seizure onset. (2) Cognitive deficits in patients with TLE are not restricted to memory only but extend to other cognitive functions. (3) there is a relationship between deficits of verbal memory and language and left TLE and visual memory and right TLE. (4) Longer duration of epilepsy, increased seizure frequency, antiepileptic polytherapy and complex partial seizures with secondary generalization are associated with cognitive dysfunctions. (5) There is an association of verbal memory, language and executive deficits with left HS and visual memory with right HS.

               So, we recommend that TLE patients should be examined by special MRI protocol for diagnosis of different pathologies which affect temporal lobe especially HS and that physicians treating epilepsy should be alert for cognitive effects of TLE, giving an ear to the patient’s complains and psychological interventions should to be made routinely as part of the overall management plan of TLE.

 

[Disclosure: Authors report no conflict of interest]

 

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الملخص العربي

 

لقد استهدف هذا البحث دراسة بعض الوظائف المعرفية وعلاقتها بالتغيرات التي قد تطرأ على الفص الصدغي من خلال صور الرنين المغناطيسي لمرضى صرع الفص الصدغي.

أجرى هذا البحث على 50 مريضاً بالغاً (28 ذكراً و 22 أنثى) يعانون من صرع الفص الصدغي تراوحت أعمارهم ما بين 18 إلى 49 سنة. وتم مقارنتهم بعشرة أشخاص أصحاء (المجموعة الضابطة) , وقد تراوحت مدة المرض في المرضى ما بين 4 أشهر إلى 360 شهرا بمعدل حدوث للحالة ما بين 7 مرات يوميا إلى مرتين في السنة. وقد تم إجراء الفحوص الآتية للمرضى و المجموعة الضابطة:

1-        الفحص الإكلينيكي للجهاز العصبي.

2-        دراسة بعض الوظائف المعرفية (الذاكرة اللفظية، الذاكرة البصرية، الوظيفة اللغوية، الوظيفة التنفيذية و وظيفة التركيب البصري).

3-        رسم المخ الكهربي (بين النوبات الصرعية).

4-        الرنين المغناطيسي للمخ.

 

وقد تلخصت النتائج فيما يلي:

وفقا للتصنيف الدولي للتشنجات (1981) كان 66% من المرضى يعانون من تشنجات صرعيه عامة, و34% من تشنجات جزئية، كما كان 66% من المرضى يتلقون عقاراً واحداً لعلاج الصرع، بينما كان 30% منتظمين على أكثر من دواء بينما لم يتلق 4% من المرضى أي علاج حتى وقت الدراسة. وقد أظهر رسام المخ الكهربائي وجود بؤرة صرعيه في 40 مريض (80%) حيث كان46٪ لهم بؤرة صرعيه جزئية في حين 34٪ منهم بؤرة صرعيه جزئية متبوعة بانتشار عام.

بينما  التصوير بالرنين المغناطيسي كان طبيعيا في 44٪، في حين كان غير طبيعيا في 56٪ في شكل مرض تصلب قرن آمون في 18% من المرضى، أورام بالمخ في 8%، تكيس في 8%، تكلس في 6%، إحتشاء مخي في 6%، ومنطقة رخوية دماغية في 10%.

أما بالنسبة لدراسة الوظائف المعرفية فقد وجدنا أن مجموعة مرضى صرع الفص الصدغي حصلوا على درجات أقل من المجموعة الضابطة في كل من الذاكرة اللفظية، الذاكرة البصرية، الوظيفة اللغوية، وظيفة التركيب البصري، و درجات أعلي من المجموعة الضابطة في الوظيفة التنفيذية و كانت هذه الفروق ذو دلالة إحصائية واضحة.

وبمقارنة تلك الوظائف المعرفية في مرضى صرع الفص الصدغي الأيمن والأيسر فقد وجد أن مرضى صرع الفص الصدغي الأيمن حصلوا على درجات أقل في الذاكرة البصرية بينما مرضى صرع الفص الصدغي الأيسر حصلوا على درجات أقل في الذاكرة اللفظية والوظيفة اللغوية وكان هذا واضح إحصائيا.

كان هناك ارتباط عكسي بين النتائج الإحصائية وبعض الوظائف المعرفية، الوظيفة اللغوية، ووظيفة التركيب البصري, والوظيفة التنفيذية ومدة المرض في حين أننا وجدنا علاقة ارتباط ايجابي ذات دلالة إحصائية بين الذاكرة اللفظية والوظيفة اللغوية والمستوى التعليمي لهؤلاء المرضى. أما بالنسبة لمجموعة المرضى الذين يتلقون أكثر من علاج للصرع, فقد حصلوا على درجات أقل من الذين يتلقون عقاراً واحداً أو لم يتلقوا أي عقار، في كل من الذاكرة اللفظية فيما يخص بذاكرة الاسترجاع المتأخر، الذاكرة البصرية، وظيفة التركيب البصري ودرجات أعلي في الوظيفة التنفيذية وكان هذا واضحاً إحصائياً.

لقد وجدنا أن المرضى الذين أظهر رسام المخ الكهربائي لديهم بؤرة صرعيه متبوعة بانتشار عام, حصلوا على درجات منخفضة بالمقارنة بالآخرين, وذلك في كل من ذاكرة الاسترجاع المتأخر، الذاكرة البصرية ووظيفة التركيب البصري وكان هذا واضحاً إحصائياً.لقد لاحظنا أن مجموعة المرضى الذين لهم منطقة مصابة بالدماغ. كما أظهر فحصهم بالرنين المغناطيسي حصلوا على درجات منخفضة, في كل من ذاكرة الاسترجاع المتأخر وظيفة التركيب البصري ودرجات مرتفعه في الوظيفة التنفيذية وكان هذا واضحاً إحصائياً.

أما بالنسبة لدراسة مرضى صرع الفص الصدغي الأيسر ذو تصلب قرن آمون فقد حصلوا على درجات منخفضة ذات دلالة إحصائية في كل من الذاكرة اللفظية فيما يخص ذاكرة الاسترجاع المباشر، وذاكرة الاسترجاع المتأخر، الوظيفة اللغوية و درجات مرتفعه للوظيفة التنفيذية والتي كان لها نفس الأهمية الإحصائية. بينما مرضى صرع الفص الصدغي الأيمن ذو تصلب قرن آمون حصلوا على درجات منخفضة ذات دلالة إحصائية في الذاكرة البصرية فقط.

ومن هنا نستنتج أهمية استخدام الرنين المغناطيسي في فحص مرضى صرع الفص الصدغي لتشخيص التغيرات المرضية المختلفة فيهم, وأيضاً نستنتج مدى تأثير مرض صرع الفص الصدغي على القدرات المعرفية وبالأخص ذي تصلب قرن آمون. ولهذا ننصح باستخدام بروتوكول خاص بالرنين المغناطيسي لتصوير الفص الصدغي في هؤلاء المرضى بالإضافة إلى زيادة الوعي بآثار المرض العقلية التي قد يكون لها آثار أخطر على المريض, من حالة الصرع نفسها, وذلك من خلال إدخال الاختبارات المعرفية في فحصهم والتي تؤدي باستخدام الحاسب الآلي لتقليل احتمالات الخطأ البشري.



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