Is 'burned-out hippocampus' syndrome a distinct electro-clinical variant of MTLE-HS syndrome?

AIM: To study the clinical, electrophysiological and imaging characteristics of patients with unilateral mesial temporal lobe epilepsy (MTLE) with contralateral ictal onset on scalp EEG, viz. 'burned-out hippocampus' syndrome (MTLE-BHS). METHODS: MTLE-BHS was defined as TLE with unilateral hippocampal sclerosis (HS) without any dual pathology on MRI and contralateral ictal onset on scalp EEG, unlike in classical hippocampal sclerosis (HS). Consecutive "MTLE-BHS" patients evaluated at our Centre for Comprehensive Epilepsy Care from January 2005 to July 2014 were studied. Twenty-five cases of classic MTLE-HS operated during the same period were also analyzed for comparison. RESULTS: Seventeen patients were diagnosed to have MTLE-BHS. Mean age of seizure onset was 9.5±7.7years and the mean duration of epilepsy was18.2±7.3years. Epigastric aura was more common in MTLE-HS and fear, secondary generalized seizures and temporal polar changes on MRI were more prevalent in the MTLE-BHS subgroup. In the latter group, five (29%) exhibited seizure semiology and 2 (12%) had interictal discharges discordant to the side of MTS. Eight (47%) patients in the MTLE-BHS sub-group had normal medial temporal volume on Scheltens scale. Eight patients among MTLE-BHS underwent surgery (4 following intracranial monitoring that localized to the side of HS) with Engel class I outcome at 1year follow-up in 6 and Engel class II outcome in 2. CONCLUSION: Attenuation of ipsilateral fast ictal rhythms on scalp EEG as well as neocortical changes are likely to be deterministic factors for MTLE-BHS as opposed to the severity of hippocampal atrophy. Considering good post-operative outcomes, intracranial monitoring for surgical selection is not mandatory in MTLE-BHS despite discordant semiology and ictal onset, in the presence of inter-ictal, functional imaging and neuropsychology data concordant to the side of HS.

Memory outcome following left anterior temporal lobectomy in patients with a failed Wada test.

PURPOSE: This study aimed to compare the memory outcome following left anterior temporal lobectomy (ATL) between patients with a failed Wada test and patients who passed the Wada test. METHODS: From 1996 to 2002, we performed the Wada test on all patients with unilateral left mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and concordant electroclinical data before ATL. We used a 12-item recognition paradigm for memory testing and awarded a score of +1 for each correct response and -0.5 for each incorrect response. No patient was denied surgery on the basis of Wada scores. We assessed cognitive and memory functions using the Wechsler Adult Intelligence Scale and the Wechsler Memory Scale preoperatively and at one year after ATL. We compared the number of patients who showed decline in memory scores, as per the published reliable change indices, between the patients with a failed Wada test and the patients who passed the Wada test. RESULTS: Out of the 116 eligible patients with left MTLE-HS, 88 underwent bilateral Wada test, while 28 underwent ipsilateral Wada test. None of them developed postoperative amnesia. Approximately, one-third of patients with a failed Wada memory test when the failure was defined as a contralateral score of <4, as an ipsilateral score of >8, and as an asymmetry score of <0. The patients with Wada memory failure had a longer pre-ATL duration of epilepsy (p<0.003). The memory and quality-of-life outcomes did not differ between the group with a failed Wada memory test and the group who passed the Wada memory test. The results remained the same when analyses were repeated at various other cutoff points. CONCLUSION: The patients with left MTLE-HS with concordant electroclinical, MRI, and neuropsychological data should not be denied ATL solely on the basis of Wada memory test results.

A critical evaluation of the lateralizing significance of material-specific memory deficits in patients with mesial temporal lobe epilepsy with hippocampal sclerosis.

To critically assess the value of material-specific memory deficits in lateralizing temporal lobe dysfunction preoperatively, we compared the neuropsychological data of 50 consecutive patients with unilateral mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS; right: 31, left: 19) with those of 50 age- and education-matched healthy control subjects. On case-control comparison, both the subcohorts with left and right MTLE-HS performed poorly on intelligence tests, in addition to individual memory tests. However, comparison of the verbal and visual memory functions between subcohorts with right and left MTLE-HS revealed that learning trials and delayed word list recall were the only tests that hypothesized left temporal lobe dysfunction. We conclude that material-specific memory deficits are largely test driven, but there is a lateralizing role for task-specific deficits in left MTLE-HS. Although neuropsychological data help to define baseline neuropsychological impairment, caution should be exercised in interpreting the lateralizing value of material-specific memory deficits prior to surgery.

Sexual desire and satisfaction after resective surgery in patients with mesial temporal lobe epilepsy with hippocampal sclerosis.

Utilizing a questionnaire, we inquired about the self-perceived sexual behavior of 50 married males with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) before and after anterior temporal lobectomy (ATL) and compared the results with those of 50 age-matched healthy married males. The sexual desire and satisfaction of the patients were poor when compared to the controls. Although a majority of the sexual domains improved following ATL, even after a median duration of five years, the sexual status of the patients did not match with that of the controls. Those who, after ATL, were seizure free, had one or no antiepileptic drug (AED) and had an EEG without epileptiform abnormalities achieved a better sexual outcome. We conclude that sexual dysfunction is frequent in male patients with MTLE-HS. They require preoperative assessment to identify their sexual inadequacies as well as counseling about the expected post-ATL sexual outcome. Discontinuation of enzyme-inducing AEDs facilitates post-ATL improvement in sexual function.

Dementia in Kerala, South India: prevalence and influence of age, education and gender.

BACKGROUND: Data on the prevalence of dementia in India with a large and aging population is scant. We studied prevalence of AD and dementia in Kerala, South India, and effects of age, education and gender on it. METHODS: 2-phase survey on 2466 individuals aged > or = 55 years living in community. Men constituted 41%, < 75 years age in 76.9% and education > or = 4 years in 69.6%. Screening (Phase I) using the instrumental activity of daily living scale for the elderly (IADL-E) and the Addenbrooke's cognition examination (ACE). Diagnostic-assessment (Phase II) was in 532 screen-positives and 247 (10%) screen-negatives. RESULTS: 93 (3.77%) > or = 55 years and 81 (4.86%) > or = 65 years of age had dementia. Age adjusted (against US-population in 2000) dementia (and AD) rates were 4.86% (1.91%) in age > or = 55 years and 6.44% (3.56%) in > or = 65 years. Odds for dementia (and AD) were high with increasing-age 5.89 (15.33) in 75-84, 13.23 (25.92) > or = 85 years, and in women 1.62 (2.95); and low 0.27 (0.16) if education was > or = 9 years. Age and low education increased dementia. Age and female gender increased AD. CONCLUSION: Prevalence of dementia and AD is higher than any reported from the subcontinent suggesting that dementia in Kerala in South India is not uncommon. Increasing age increased dementia and AD. Low-education is associated with dementia and female-gender with AD.

Impaired facial emotion recognition in patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS): Side and age at onset matters.

To define the determinants of impaired facial emotion recognition (FER) in patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS), we examined 76 patients with unilateral MTLE-HS, 36 prior to antero-mesial temporal lobectomy (AMTL) and 40 after AMTL, and 28 healthy control subjects with a FER test consisting of 60 items (20 each for anger, fear, and happiness). Mean percentages of the accurate responses were calculated for different subgroups: right vs. left MTLE-HS, early (age at onset <6 years) vs. late-onset, and before vs. after AMTL. After controlling for years of education, duration of epilepsy and number of antiepileptic drugs (AEDs) taken, on multivariate analysis, fear recognition was profoundly impaired in early-onset right MTLE-HS patients compared to other MTLE patients and control subjects. Happiness recognition was significantly better in post-AMTL MTLE-HS patients compared to pre-AMTL patients while anger and fear recognition did not differ. We conclude that patients with right MTLE-HS with age at seizure onset <6 years are maximally predisposed to impaired fear recognition. In them, right AMTL does not further worsen FER abilities. Longitudinal studies comparing FER in the same patients before and after AMTL will be required to refine and confirm our cross-sectional observations.

Hippocampal activations in mesial temporal lobe epilepsy due to hippocampal sclerosis- an observational study on intramural encoding-delayed recall paradigms using task-based memory fMRI.

OBJECTIVES: To validate concurrent utility of within-scanner encoding and delayed recognition-memory paradigms to ascertain hippocampal activations during task-based memory fMRI. METHODS: Memory paradigms were designed for faces, word-pairs and abstract designs. A deep-encoding task was designed comprising of a total of 9 cycles run within a 1.5T MRI scanner. A recall session was performed after 1 h within the scanner using an event-related design. Group analysis was done with 'correct-incorrect' responses applied as parametric modulators in Statistical Parametric Mapping version 8 using boot-strap method to enable estimation of laterality indices (LI) using custom anatomical masks involving the medio-basal temporal structures. RESULTS: Twenty seven subjects with drug-resistant mesial temporal lobe epilepsy due to hippocampal sclerosis (MTLE-HS) [17 patients of left-MTLE and 10 patients of right-MTLE] and 21 right handed age-matched healthy controls (HC) were recruited. For the encoding paradigm blood oxygen level dependent (BOLD) responses in HC demonstrated right laterality for faces, left laterality for word pairs, and bilaterality for design encoding over the regions of interest. Both right and left MTLE-HS groups revealed left lateralisation for word-pair encoding, bilateral activation for face encoding, with design encoding in right MTLE-HS demonstrating a left shift. As opposed to lateralization shown in controls, group analysis of cued-recall BOLD signals acquired within scanner in left MTLE-HS demonstrated right lateralization for word-pairs with bilaterality for faces and designs. The right MTLE-HS group demonstrated bilateral activations for faces, word-pairs and designs. CONCLUSION: Recall-based fMRI paradigms indicate hippocampal plasticity in MTLE-HS, maximal for word-pair associate recall tasks.

Corpora amylacea in mesial temporal lobe epilepsy: clinico-pathological correlations.

PURPOSE: To investigate the electro-clinical significance of premature accumulation of corpora amylacea (CoA) in the resected hippocampus of patients with medically refractory mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). METHODS: We compared the clinical and EEG characteristics, and post-operative seizure outcome of 373 (mean age 29.4 years, range 7-55 years) surgically treated MTLE-HS patients with (MTLE-HS-CoA(+), n=129 [34.5%]) and without (MTLE-HS-CoA(-), n=244 [65.5%]) CoA. RESULTS: Age at surgery was significantly higher and duration of epilepsy before surgery was significantly longer for MTLE-HS-CoA(+) patients compared to MTLE-HS-CoA(-) patients. Although the distribution of interictal epileptiform EEG abnormalities did not differ, type 1 ictal EEG pattern was more frequent in MTLE-HS-CoA(+) patients. Among the 21 patients with major interictal psychosis detected prior to epilepsy surgery, 19 (90.5%) belonged to MTLE-HS-CoA(+) group. Schizophrenia-like psychosis was most prevalent. The post-operative seizure-free outcome was comparable, but significantly more MTLE-HS-CoA(-) patients were free of antiepileptic drugs. CONCLUSIONS: Overall, our observations support the hypothesis that the pathological process in MTLE-HS is progressive. MTLE-HS-CoA(+) patients are predisposed to increased psychiatric morbidity. In vivo detection of hippocampal CoA accumulation in the future will help us to understand the neurobiological significance of this phenomenon.

Mini mental state examination and the Addenbrooke's cognitive examination: effect of education and norms for a multicultural population.

OBJECTIVE: To derive population norms on the Malayalam adaptation of Addenbrooke's Cognitive Examination (M-ACE) and the inclusive Malayalam mini mental state examination (M-MMSE). MATERIALS AND METHODS: Education-stratified norms were obtained on randomly selected cognitively unimpaired community elders (n = 519). RESULTS: Valid data on norms was available on 488 subjects (age 68.5 +/- 7.1 and education 7.9 +/- 5.4). Education and age, but not gender had a significant effect on both M-ACE and M-MMSE. When compared to the effect of age, the effect of education was sevenfold more on the M-ACE and ninefold more on the M-MMSE. The mean composite score on the M-ACE (and the M-MMSE) was 42.8 +/- 9.8 (14.9 +/- 3.1) for those with 0 (n = 72), 55.9 +/- 12.5 (19.7 +/- 4.1) with 1-4 (n = 96), 62.6 +/- 11.4 (21.9 +/- 3.7) with 5-8 (n = 81), 77 +/- 10.2 (25.7 +/- 2.4) with 9-12 (n = 136) and 83.4 +/- 7.2 (26.7 +/- 1.6) with > 12 (n = 103) years of formal education. CONCLUSIONS: Education has the most potent effect on performance on both M-ACE and M-MMSE in the Indian cohort. Education-stratified scores on the M-ACE and the M-MMSE, will provide a more appropriate means of establishing the cognitive status of patients. It is also our feeling that these cut-off scores will be useful across India.

Qualitative aspects of learning, recall, and recognition in dementia.

OBJECTIVE: To determine whether learning and serial position effect (SPE) differs qualitatively and quantitatively among different types of dementia and between dementia patients and controls; we also wished to find out whether interference affects it. MATERIALS AND METHODS: We administered the Malayalam version of the Rey Auditory Verbal Learning Test (RAVLT) to 30 cognitively unimpaired controls and 80 dementia patients [30 with Alzheimer's disease (AD), 30 with vascular dementia (VaD), and 20 with frontotemporal dementia (FTD)] with mild severity on the Clinical Dementia Rating Scale. RESULTS: All groups were comparable on education and age, except the FTD group, who were younger. Qualitatively, the learning pattern and SPE (with primacy and recency being superior to intermediate) was retained in the AD, VaD, and control groups. On SPE in free recall, recency was superior to intermediate in the FTD group (P < 0.01 using Bonferroni correction). On recognition, the AD and VaD groups had more misses (P < 0.01), while the FTD group had more false positives (P < 0.01). CONCLUSION: Quantitative learning is affected by dementia. The pattern of qualitative learning remains unaltered in dementia in the early stages.