Auditory Temporal Ordering in Patients with Medial Temporal Lobe Epilepsy with and without Hippocampal Sclerosis
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.314569
Source of Support: None, Conflict of Interest: None
Keywords: Auditory temporal ordering, central auditory processing, duration pattern test, medial temporal lobe epilepsyKey Message: MTLE both with HS and without HS affects ATO, a CAP skill. CAP is crucial to speech perception.
Temporal processing is important for speech recognition and is the basic component of central auditory processing (CAP)., Temporal processing encompasses four sub-processes: (a) temporal resolution, (b) temporal patterning, (c) temporal integration, and (d) temporal masking. Auditory temporal ordering (ATO) is a temporal patterning task and refers to the processing of two or more sounds in their order of occurrence in time. ATO can be evaluated using duration pattern test (DPT). Subjects' responses on DPT require the interaction of both hemispheres and corpus callosum. DPT is found to be sensitive to central pathologies.,,,
Temporal lobe epilepsy (TLE) with hippocampal sclerosis forms a major subgroup of patients with TLE. Medial temporal lobe epilepsy (MTLE) can cause damage to the neocortex, and corpus callosum., Hence, it is posited that MTLE precipitates auditory processing disorder (APD). Researchers employing auditory behavioral,,,,,,,,, and electrophysiological measures,,, have reported APD in patients with TLE. However, very few studies have looked into CAPD in distinct homogeneous subgroups such as MTLE with hippocampal sclerosis (MTLE + HS) and without hippocampal sclerosis (MTLE-HS). The current study was aimed to evaluate ATO using DPT in patients with “MTLE + HS” and “MTLE-HS” as well as in their subgroups, right MTLE with HS (RMTLE + HS), left MTLE with HS (LMTLE + HS), right MTLE without HS (RMTLE-HS), and left MTLE without HS (LMTLE-HS).
Test universe: Department of Speech pathology and Audiology and Department of Neurology, National institute of mental health and neurosciences, Bangalore, Karnataka, India.
Patients (N = 100; M:F = 66:34) who were candidates for pre-surgical evaluation for drug-resistant epilepsy participated in the study. All were under multiple antiepileptic drug regimes. Among them, 50 were “MTLE + HS” (M:F = 29:21) and 50 were “MTLE-HS” (M:F = 37:13). Age range-matched normal healthy volunteers (n = 50; M:F = 31:19) formed the control group. The sub-groups in the clinical group were RMTLE + HS (n = 23; M:F = 13:10), LMTLE + HS (n = 27; M:F = 16:11), RMTLE-HS (n = 22; M:F = 16:6), and LMTLE-HS (n = 28; M:F = 21:7).
The patients were first identified and evaluated by an epileptologist (PS and SS). Detailed clinical history, interictal electroencephalography (EEG), and video–EEG recordings constituted the neurological evaluation. Magnetic resonance imaging (MRI) was carried out on a 3-T machine (Philips Achieva) and the interpretation was done by the MRI specialist (JS) based on volume loss, signal changes, loss of normal architecture, and loss of hippocampal internal digitization, for the diagnosis of MTLE + HS. All subjects were right-handed individuals in the age range of 15 to 50 years. All had a bilateral normal hearing sensitivity (≤25 dBHL; 250 Hz to 8 KHz) on audiometry for air conduction (based on the classification of Goodman, 1965). Subjects with a history/complaint of acute or chronic middle ear infections were excluded. With specific to the clinical group, patients who had premorbid neurological/psychiatric disorders, other types of epilepsy, and undergone surgical intervention for epilepsy earlier were excluded. A pre-recorded DPT was routed through a calibrated clinical audiometer. The test was carried out in a sound-treated double room. The study had the approval of the institutional ethics committee of the study center. Further, the subjects gave their written informed consent for the study.
Duration pattern test
The DPT has a sequence of three consecutive 1000 Hz tones with an inter-stimulus interval of 300 ms and they were either long (L) or short (S) in duration. The long tone was of 500 ms and the short was of 250 ms duration with a rise/fall time of 10 ms. Among the three tones, one differed from the other two in the sequence. Six different response sequences (LLS, LSL, LSS, SLS, SLL, and SSL) were possible in the test. A total of 20 such stimuli (three-tone sequences) were presented monaurally at 50dB sensational level with reference to speech recognition threshold. The subjects were instructed to respond to each stimulus presentation with a verbal description of the sequence heard. The total number of correct responses (raw score) were calculated for each ear separately referred as DPT right and DPT left which were further converted into percentages (DPT right % and DPT left %). The higher percentage of correct response indicated better ATO. Practice items were provided to each subject to ensure their understanding of the task before the actual test administration.
Statistical analysis was done using SPSS 22.0 (SPSS, Chicago, IL, USA) software package. ANOVA (post hoc: Dunnett's two-sided) was done to evaluate the differences between the control and the patient groups. ANOVA (post hoc: Bonferroni) was used to compare between the patient groups. To check for the ear effect, the right and the left ear scores were compared using paired sample t-test. The relation between the phenotypes and the test measures were studied using Pearson's correlation. An independent t-test was performed to study the effect of phenotypes.
There was no significant difference between the groups with respect to demographic variables [Table 1] viz., mean age and gender distribution (for all subject groups), onset, duration of seizures, and mini mental state examination (MMSE) score (for both patient groups and their subgroups).
The mean percentage of correct response for the control group and the patient groups are given in [Table 2]. The control group had significantly (P < 0.001) higher scores compared to the “MTLE + HS” and “MTLE − HS” groups (DPT Right%: F (2,147) = 46.56 and DPT left%: F (2,147) = 48.29) and its subgroups (DPT Right%: F (4,145) = 23.34 and DPT left %: F (4,145) = 25.39) than other groups. However, there were no significant differences between the clinical groups.
A right and left ear comparison (paired t-test) did not reveal significant differences for both control and patient groups (clinical and its subgroups). To evaluate the effect of phenotypes, subjects were sub-categorized based on cutoff values. The cutoff values (based on median values) were 10 years for age at onset and 15 years for the duration of seizure. In addition, the patients were categorized based on the seizure frequency (≥2/week or ≥2/month), last seizure attack (within 3–7 days: within 8 days to 1 month) and drug effect (two drugs or more). There was no significant difference (independent t-test) between any of the phenotypic subgroups. Further, the age at onset and duration of seizures did not reveal any correlation (Pearson's) with the ATO performance in any of the patient groups.
To differentiate the normal and abnormal scores, a cutoff value of 2 SD below the mean scores of the control group was used (Museik, 2005). Accordingly, 75% cutoff value was considered for both ears. On an average, around 68% of the patients had performed below the cutoff score [Table 3].
The medial temporal lobe has a role in CAP.,,, The APD has been documented in patients with TLE.,,,,,,,,,,,,, The nature of APD in these patients seems to be a covert phenomenon not otherwise reported by the patients. Further, researchers had reported a differential effect of various phenotypes such as age at onset, duration, frequency, and last seizure attack as well as the drug regime on AP skills.,
In the current study, we report the performance of MTLE patients and their subgroups on DPT. The patient groups (”MTLE+HS” and “MTLE−HS”) and their subgroups (”RMTLE+HS,” “LMTLE+HS,” “RMTLE−HS,” and “LMTLE−HS”) have demonstrated poorer scores compared to the control group, indicating ATO dysfunction. The mean percentage of correct response for the patient groups ranged from 44.6% to 63.5% compared to the control group score of >90%. Poorer performance on DPT as well as on dichotic digits test (DDT) in children with TLE has been reported in an earlier study by Cranford et al (1996). The mean right DPT and left ear scores were 34.4 ± 13.03% and 38.2 ± 24.83%, respectively. The authors had compared the pre-surgical and post-surgical (for epilepsy) scores in the same group of children and found that poorer performance persisted even after surgery. Similar findings have been reported in adults. The authors studied the impact of epilepsy surgery on CAP function in patients (n = 22; mean age 40.41 ± 10.31 years) with “MTLE-HS”. Their findings revealed no significant difference between pre- and post-surgery on DPT, frequency pattern test (FPT), and dichotic speech test (DST). The pre-operative DPT scores were around 70% in the “MTLE−HS'' group and the subgroups (RMTLE − HS and left MTLE-HS) compared to the cutoff (81%), indicating ATO dysfunction.
CAP dysfunctions in patients with TLE generally have been studied as a whole group. Meneguello et al. (2006) in their study (n = 8; age = 22 to 51 years) reported poorer performance on DPT, DDT, and nonverbal dichotic test except sound location test in patients with TLE. The average DPT right and left score for the patient groups was 53.3 and 56.6%, respectively, and that of the control group was 85.2 and 85.7%, respectively. In a detailed study on distinct TLE subgroups, Han et al. (2011) recruited patients (n = 28) with hippocampal sclerosis (right = 10, left = 8, and bilateral = 2) and without hippocampal sclerosis (n = 8). The same patients were subcategorized with reference to seizure foci (right = 15, left = 10, and bilateral = 3). The authors reported poorer scores (mean: 73.1 ± 22.1%) on FPT, DPT, and DDT in patients compared to the normal cutoff score (81%), indicating ATO dysfunction. The findings of our study corroborate with the findings of the above studies.
In the current study, the differences between the control and the patient groups were statistically significant. However, no significant effect was observed among those with and without HS. This implicates that there is no distinct effect of lesion or seizure on ATO skill. This is similar to the findings on DPT reported by Han et al. (2011). The authors had further reported that on FPT measure, the patients with HS performed significantly poor than without HS. A similar poor performance by the “TLE with HS” group has been reported on rapid auditory processing task. However, in the current study, FPT, as well as rapid auditory processing task, was not included as a part of the test protocol.
The non-lesion side of the clinical groups too showed poor scores in the current study. Further, a comparison between the right and the left ear (lesion vs. non lesion side) did not yield any significant differences. A similar finding has been reported by Meneguello et al. (2006). The observed bilateral deficit could be attributed cumulatively to the nature of the test (DPT) employed and the underlying pathology. First, unilateral cerebral lesion causes bilateral reduction of DPT scores, as both hemispheres contribute during DPT testing., Second, bilateral deficits have been reported in unilateral TLE patients using other CAP test measures.,, Further, bihemispheric abnormality,,, and damage to corpus callosum, have been documented in patients with unilateral TLE.
This study also documents no significant difference between the seizure phenotypic categories (early vs. late onset, less vs. long duration, less vs. more frequency, recent vs. early attack, and less number vs. more number of drugs) on the DPT measures. Similar results are reported in the literature. Further, in the current study, the age at onset and duration of seizures did not show any significant correlation with that of the DPT measures. Contrarily, Han et al. (2011) reported a negative correlation of DPT and dichotic measures with respect to the duration of seizures. However, they did not find a correlation on FPT measure and also with respect to age at seizure onset. Similar to the current study, Chi Chen et al. (2001) in their study reported no correlation with respect to age at onset and duration of seizure in relation to auditory P300 measure.
To find the number of subjects having an abnormal score, a cutoff value of 75% was considered in the current study. Based on this criterion, it was found approximately 68% of patients had an abnormal score. Han et al. (2011) reported that 57.1% patients with TLE as having abnormal scores. The difference between our study and of theirs could be due to slightly higher cutoff score (81%) considered by the authors compared to our study. Also, in the present study, the cutoff score was derived out of age range-matched control group and the sample size was on the higher side. Further, probing of the results reveal higher failure percentage in patients with left hemisphere damage (LMTLE + HS and LMTLE-HS) compared to those with right hemisphere damage (RMTLE + HS and RMTLE-HS). This could be due to the fact that the left hemisphere is generally the language dominant making the verbal responses difficult during the DPT.
The current study implicates ATO deficits in patients with MTLE with and without hippocampal sclerosis and in their distinct subgroups. In agreement with previous studies, the current study further strengthens and justifies the role of audiological tests in unravelling APD in patients with TLE. These deficits seem to be a covert phenomenon, and hence require a thorough understanding of its pathophysiological basis and its overall effect on quality of life of the individuals with TLE. Future studies encompassing various central auditory measures should focus towards profiling auditory skills deficits and expand it to remediation strategies. This is more pertinent particularly in the school-going population as APD secondary to TLE may have a direct impact on their learning outcomes.
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[Table 1], [Table 2], [Table 3]