Breaking the age barrier: Epilepsy surgery in septuagenarians.

Resective epilepsy surgery (RES) has traditionally been offered to young patients (<50years). The reservation about offering RES to the elderly is multifactorial with their advanced age and comorbidities being the primary reason. The elderly age group (≥65years of age) is one of the fastest growing populations. The arbitrary age limits for RES need reconsideration in the face of an ever increasing elderly population. Considering such changes in demographics, we report the first case series in the literature of seven septuagenarians who underwent RES in the form of anterior temporal lobectomy (ATL). The 10-year median survival probability based on their comorbidities and age was more than 50%. Six patients had good surgical outcome (Engle I/II) with four of them being completely free of disabling seizures after a median follow-up of almost 2years. No significant medical or surgical morbidity was observed. However, three out of the four patients undergoing pre- and post-RES neuropsychological testing showed decline in memory function. Seizure-related injuries were noted in four out of seven patients and may have been a motivation to proceed with RES in our cohort. Our experience suggests that RES can be a safe and effective therapy in well-selected, septuagenarian patients with drug-resistant epilepsy. Neuropsychological outcomes after RES in this population need further evaluation.

Histopathologic substrate of drug-resistant epilepsy in older adults and the elderly undergoing surgery.

Patients 60 years or older are one of the highest risk age groups for development of epilepsy. Clinical and neuroimaging analysis has typically accounted for etiology in two-thirds of these patients, while the data on histopathology are lacking. We provide the first analysis of the histopathological substrates underlying drug-resistant epilepsy (DRE) in older adults/elderly patients who underwent resective epilepsy surgery (RES) at Cleveland Clinic. A total of 78 patients (mean age ± standard deviation: 64.7 ± 3.7 years; 59% female) were included in the study. The most common pathologies included hippocampal sclerosis (HS; 35.9%; all visible on magnetic resonance imaging [MRI]), focal cortical dysplasia (FCD; 25.6%) and remote infarct/ischemic changes (12.8%). Underlying pathology did not differ significantly between the patients achieving a good seizure outcome (Engel class I; 77% [47 of 61 patients]) and the rest of the cohort. With one exception, all MRI-negative cases had FCD type Ib. A receiver-operating characteristic (ROC) curve analysis found a significant association (P = 0.002) between seizure-onset age and HS, whereby the odds of its presence were reduced by 4% for every 1 year increase in the age at seizure onset. The model showed that the age cutoff for seizure onset predicting HS was 43 years, with a negative predictive value of 81.6%. None of the 14 patients with late-onset epilepsy (≥60 years of age) were found to have HS; they mostly had acquired lesions. Our study provides histopathologic evidence for the diminished role of late-onset HS in DRE in older adults/elderly who undergo RES.

Extra operative intracranial EEG monitoring for epilepsy surgery in elderly patients.

OBJECT: The objective of the study is to investigate and report our experience with extra operative intracranial EEG monitoring for evaluation of epilepsy surgery among elderly (≥ 60 years) patients. METHODS: After IRB approval, we searched our prospectively maintained epilepsy surgery database to find patients who underwent eiEEG at the age of 60 years or older. Electronic medical records were reviewed to extract clinical and surgery-related information. Patients who underwent resective epilepsy surgery after eiEEG and had at least 1 year of clinical follow-up were assessed for seizure outcome. Categorical and continuous variables were compared using Pearson chi-square and Student's t-test, respectively. RESULTS: A total of 21 patients, with 13 (62%) women, underwent eiEEG in our center at the age of 60 years or older. The mean age at time of implantation was 63.8 ±â€¯2.7 years. Sub-dural grids (SDG) were implanted in five (24%) patients, whereas sixteen (76%) patients underwent stereo-EEG (SEEG) implantation. Median number of contacts in SDG were 106 (56-136) and depth electrodes in SEEG were 12 (9-14). There were 2 complications, including one mortality due to intracerebral hemorrhage. Sixteen (76%) patients underwent respective epilepsy surgery after eiEEG and eleven (69%) achieved Engel class I outcome on the last follow-up [mean follow-up duration of 2.7 (± 1.8) years]. CONCLUSION: We noticed an increased utilization of eiEEG in elderly patients after the introduction of SEEG at our center. Overall, we found that eiEEG can help achieve good seizure outcomes in the elderly population. However, the one eiEEG-related mortality serves a word of caution about the potential risks in this population.

Time to push the age limit: Epilepsy surgery in patients 60 years or older.

Objective: To summarize the existing literature on resective epilepsy surgery (RES) in older adults (≥60 years old) and examine seizure and neuropsychological outcomes in a single-center large cohort of older adults undergoing RES and their comparison to a consecutive, younger (25- to45-year-old) adult population who underwent RES in routine clinical practice. Methods: First, a comprehensive literature review was performed. Then, we identified older adults who underwent RES at our center (2000-2015). Outcome analysis was performed on patients who had ≥1 year of clinical follow-up. A younger cohort of patients who underwent RES during the same period was selected for comparison. The 2 groups were compared with respect to demographic and disease variables as well as key clinical outcomes. Results: Seizure outcomes on 58 older patients were reported in existing literature; 72% achieved Engel class I outcome ≥1 year postoperatively. Sixty-four older adults underwent RES at our center, accounting for 2.8% of all RES during the study period. A total of 51 older adults (Mage = 65) among them had ≥1-year clinical follow-up; 80% achieved Engel I outcome after a mean follow-up of 3.2 years. This was comparable to the 68% Engel class I outcome among 50 consecutive younger adults, despite later age of onset, longer epilepsy duration, and more comorbidities (all p < 0.001) among older adults. The majority (86%) of older adults were referred to our center after years of suffering from drug-resistant epilepsy. There were no group differences in surgical complications. However, 1 older adult passed away post-RES. There was no difference in post-RES neuropsychological outcomes compared to younger adults, except significantly higher number of older adults showed a decline in confrontational naming. Significance: RES in well-selected older adults is a safe and effective therapy, and advanced age should not preclude consideration of surgical therapy in older adults with pharmacoresistant epilepsy.

Comparison of reorganization of the somatosensory system in rats that sustained forelimb removal as neonates and as adults.

Studies of sensory pathways in several species indicate that the extent and form of reorganization resulting from deafferentation early in life vs. adulthood are not the same. The reasons for such differences are not well understood. To gain further insight into age-dependent mechanisms of reorganization, this study compared the consequences of neonatal vs. adult forelimb amputation in rats at multiple levels of the sensory pathway, including primary somatosensory cortex, brainstem, and dorsal root ganglia. At the cortical level, the average area of the functional forelimb-stump representation from rats amputated as adults was significantly smaller (P < 0.05) than that of neonatally amputated rats (4.3 +/- 1.3 mm(2) vs. 6.6 +/- 1.5 mm(2), respectively). At the brainstem level, neonatally amputated rat cuneate neurons possessed the following responsivities: 20% stump responsive, 40% responsive to both stump and hindlimb, 30% responsive to another body region, and 10% unresponsive. In contrast, cuneate neurons of adult amputated rats were 70% stump responsive, 2% responsive to both stump and hindlimb, and 30% unresponsive. A significantly (P < 0.001) greater percentage of the C(6)-C(8) dorsal root ganglia neurons of adult amputated rats were unresponsive to peripheral stimulation vs. neurons from neonatally amputated rats (48% vs. 16%, respectively). These results indicate that the reorganization that occurs in response to forelimb amputation at birth vs. adulthood is distinctly different at each of these levels of the dorsal column-medial lemniscal pathway. Possible mechanisms to account for these differences are considered.

Do observer and self-reports of ictal eye closure predict psychogenic nonepileptic seizures?

PURPOSE: Diagnostic delay in distinguishing psychogenic nonepileptic seizures (PNES) from epileptic seizures may result in unnecessary therapeutic interventions and higher health care costs. Previous studies demonstrated that video-recorded eye closure is associated with PNES. The present study prospectively assessed whether observer or self-report of eye closure could predict PNES, prior to video-EEG monitoring. METHODS: Adults referred to an epilepsy monitoring unit (EMU) were prospectively enrolled into the study. At baseline, self-report of eye closure was assessed by questionnaire, and observer report was obtained by interview. Physicians viewed video clips independent of EEG tracings and determined the duration of eye closure during PNES and epileptic seizures. We evaluated whether video-recorded eye closure identified an episode as PNES using random effects models that accounted for episode clustering by subject. The utility of observer and self-report of eye closure in predicting a diagnosis of PNES was tested using logistic regression. RESULTS: Of 132 enrolled subjects, 112 met study criteria during EMU stay for either PNES (n = 43, 38.4%) or epilepsy (n = 84, 75.0%). Fifteen of the 43 PNES subjects (34.9%) had coexisting epilepsy. Self and observer reports of eye closure were neither sensitive nor specific for the diagnosis of PNES. Self-report of eye closure more accurately predicted actual video-recorded eye closure than observer report. Video-recorded eye closure was 92% specific, but only 64% sensitive for PNES identification. DISCUSSION: Neither observer nor self-report of eye closure, prior to VEEG monitoring, predicts PNES. Video-recorded eye closure may not be as sensitive an indicator of PNES as previously reported.

Role of development in reorganization of the SI forelimb-stump representation in fetally, neonatally, and adult amputated rats.

Rats that sustain forelimb removal on postnatal day (P) 0 exhibit numerous multi-unit recording sites in the forelimb-stump representation of primary somatosensory cortex (SI) that also respond to hindlimb stimulation when cortical GABAA+B receptors are blocked. Most of these hindlimb inputs originate in the medial SI hindlimb representation. Although many forelimb-stump sites in these animals respond to hindlimb stimulation, very few respond to stimulation of the face (vibrissae or lower jaw), which is represented in SI just lateral to the forelimb. The lateral to medial development of SI may influence the capacity of hindlimb (but not face) inputs to "invade" the forelimb-stump region in neonatal amputees. The SI forelimb-stump was mapped in adult (>60 days) rats that had sustained amputation on embryonic day (E) 16, on P0, or during adulthood. GABA receptors were blocked and subsequent mapping revealed increases in nonstump inputs in E16 and P0 amputees: fetal amputees exhibited forelimb-stump sites responsive to face (34%), hindlimb (10%), and both (22%); neonatal amputees exhibited 10% face, 39% hindlimb, and 5% both; adult amputees exhibited 10% face, 5% hindlimb, and 0% both, with approximately 80% stump-only sites. These results indicate age-dependent differences in receptive-field reorganization of the forelimb-stump representation, which may reflect the spatiotemporal development of SI. Results from cobalt chloride inactivation of the SI vibrissae region and electrolesioning of the dysgranular cortex suggest that normally suppressed vibrissae inputs to the SI forelimb-stump area originate in the SI vibrissae region and synapse in the dysgranular cortex.