Management of epilepsy in older adults: A critical review by the ILAE Task Force on Epilepsy in the elderly.

Older adults represent a highly heterogeneous population, with multiple diverse subgroups. Therefore, an individualized approach to treatment is essential to meet the needs of each unique subgroup. Most comparative studies focusing on treatment of epilepsy in older adults have found that levetiracetam has the best chance of long-term seizure freedom. However, there is a lack of studies investigating other newer generation antiseizure medications (ASMs). Although a number of randomized clinical trials have been performed on older adults with epilepsy, the number of participants studied was generally small, and they only investigated short-term efficacy and tolerability. Quality of life as an outcome is often missing but is necessary to understand the effectiveness and possible side effects of treatment. Prognosis needs to move beyond the focus on seizure control to long-term patient-centered outcomes. Dosing studies with newer generation ASMs are needed to understand which treatments are the best in the older adults with different comorbidities. In particular, more high-level evidence is required for older adults with Alzheimer's disease with epilepsy and status epilepticus. Future treatment studies should use greater homogeneity in the inclusion criteria to allow for clearer findings that can be comparable with other studies to build the existing treatment evidence base.

The epidemiology of epilepsy in older adults: A narrative review by the ILAE Task Force on Epilepsy in the Elderly.

In an aging world, it is important to know the burden of epilepsy affecting populations of older persons. We performed a selective review of epidemiological studies that we considered to be most informative, trying to include data from all parts of the world. We emphasized primary reports rather than review articles. We reviewed studies reporting the incidence and prevalence of epilepsy that focused on an older population as well as studies that included a wider age range if older persons were tabulated as a subgroup. There is strong evidence that persons older than approximately 60 years incur an increasing risk of both acute symptomatic seizures and epilepsy. In wealthier countries, the incidence of epilepsy increases sharply after age 60 or 65 years. This phenomenon was not always observed among reports from populations with lower socioeconomic status. This discrepancy may reflect differences in etiologies, methods of ascertainment, or distribution of ages; this is an area for more research. We identified other areas for which there are inadequate data. Incidence data are scarcer than prevalence data and are missing for large areas of the world. Prevalence is lower than would be expected from cumulative incidence, possibly because of remissions, excess mortality, or misdiagnosis of acute symptomatic seizures as epilepsy. Segmentation by age, frailty, and comorbidities is desirable, because "epilepsy in the elderly" is otherwise too broad a concept. Data are needed on rates of status epilepticus and drug-resistant epilepsy using the newer definitions. Many more data are needed from low-income populations and from developing countries. Greater awareness of the high rates of seizures among older adults should lead to more focused diagnostic efforts for individuals. Accurate data on epilepsy among older adults should drive proper allocation of treatments for individuals and resources for societies.

Self-Wrinkling in Polyacrylamide Hydrogel Bilayers.

Swelling of a gel film attached to a soft substrate can induce surface instability, which results in the formation of highly ordered patterns such as wrinkles and folds. This phenomenon has been exploited to fabricate functional devices and rationalize morphogenesis. However, obtaining centimeter-scale patterns without immersing the film in a solvent remains challenging. Here, we show that wrinkles with wavelengths of up to a few centimeters can be spontaneously created during the open-air fabrication of film-substrate bilayers of polyacrylamide (PAAm) hydrogels. When the film of an aqueous pregel solution of acrylamide prepared on the PAAm hydrogel substrate undergoes open-air gelation, hexagonally packed dimples initially emerge on the surface, which later evolve into randomly oriented wrinkles. The formation of such self-organized patterns can be attributed to the surface instability resulting from autonomous water transport in the bilayer system during open-air fabrication. The temporal evolution of the patterns can be ascribed to an increase in overstress in the hydrogel film due to continued water uptake. The wrinkle wavelength can be controlled in the centimeter-scale range by adjusting the film thickness of the aqueous pregel solution. Our self-wrinkling method provides a simple mechanism for the generation of swelling-induced centimeter-scale wrinkles without requiring an external solvent, which is unachievable with conventional approaches.

Atrophy of the hippocampal CA1 subfield relates to long-term forgetting in focal epilepsy.

OBJECTIVE: The mechanisms underlying accelerated long-term forgetting (ALF) in patients with epilepsy are still under investigation. We examined the contribution of hippocampal subfields and their morphology to long-term memory performance in patients with focal epilepsy. METHODS: We prospectively assessed long-term memory and performed magnetic resonance imaging in 80 patients with focal epilepsy (61 with temporal lobe epilepsy and 19 with extratemporal lobe epilepsy) and 30 healthy controls. The patients also underwent electroencephalography recording. Verbal and visuospatial memory was tested 30 s, 10 min, and 1 week after learning. We assessed the volumes of the whole hippocampus and seven subfields and deformation of the hippocampal shape. The contributions of the hippocampal volumes and shape deformation to long-term forgetting, controlling for confounding factors, including the presence of interictal epileptiform discharges, were assessed by multiple regression analyses. RESULTS: Patients with focal epilepsy had lower intelligence quotients and route recall scores at 10 min than controls. The focal epilepsy group had smaller volumes of both the right and left hippocampal tails than the control group, but there were no statistically significant group differences for the volumes of the whole hippocampus or other hippocampal subfields. Multiple regression analyses showed a significant association between the left CA1 volume and the 1-week story retention (ß = 7.76; Bonferroni-corrected p = 0.044), but this was not found for the whole hippocampus or other subfield volumes. Hippocampal shape analyses revealed that atrophy of the superior-lateral, superior-central, and inferior-medial regions of the left hippocampus, corresponding to CA1 and CA2/3, was associated with the verbal retention rate. SIGNIFICANCE: Our results suggest that atrophy of the hippocampal CA1 region and its associated structures disrupts long-term memory consolidation in focal epilepsy. Neuronal cell loss in specific hippocampal subfields could be a key underlying cause of ALF in patients with epilepsy.

Characteristics of olfactory dysfunction in patients with temporal lobe epilepsy.

OBJECTIVE: To determine the characteristics of olfactory dysfunction in patients with temporal lobe epilepsy (TLE). METHODS: Odor identification was assessed using the odor stick identification test for Japanese (OSIT-J, full score 12 points) in 65 patients with TLE and in 74 controls. RESULTS: The mean OSIT-J score was significantly lower in patients with TLE (mean ±â€¯SD = 8.1 ±â€¯2.8; median = 9) than in the control subjects (mean ±â€¯SD = 10.6 ±â€¯1.1; median = 11) (P < 0.005). Olfactory dysfunction (hyposmia/anosmia) was associated with bilateral seizure foci and older age of onset in TLE. Patients who underwent temporal lobectomy for hippocampal sclerosis did not show significant decline after long-term recovery. The Indian ink part of OSIT-J was useful for the detection of olfactory deficits in patients with TLE (sensitivity = 47%, specificity = 93%). Patients with TLE tended to have preserved olfactory ability for stimulating odors and for familiar odors of daily life. SIGNIFICANCE: We observed characteristic odor identification deficits for individual odors used in OSIT-J. Our study findings provide deeper insight into the underlying mechanism of olfactory function in patients with TLE and may be beneficial in the clinical management of these patients.

Abnormal repolarization: A common electrocardiographic finding in patients with epilepsy.

BACKGROUND: Recently, certain forms of early repolarization (ER) on electrocardiograms (ECGs) have been considered a possible marker of increased sudden cardiac death risk. The frequency, characteristics, and clinical follow-up with which these forms of ER are present in epilepsy patients, and whether or not abnormal ER contributes to sudden unexplained death in epilepsy patients (SUDEP) is unknown. METHODS AND RESULTS: The amplitude of J peak and ST-segment morphology after ER on 12-lead ECGs were assessed in 354 epilepsy patients (age, 33 ± 16 years; 54% men) and 140 age- and sex-matched control subjects (age, 31 ± 12 years; 50% men). Abnormal ER prevalence (J-wave amplitude ≥0.1 mV) was greater in epilepsy patients (19.8%) compared with controls (8.6%; P = 0.002) in inferior ECG leads but not in lateral leads ( P = 0.40). ER with a horizontal or descending ST segment was also more prevalent in epilepsy patients ( P < 0.001). After introducing antiepileptic drugs in 36 epilepsy patients, there were no significant ER changes. Similarly, in 64 epilepsy patients with seizure suppression, ER comparison before and after seizure control revealed no significant changes. Male gender was the only significant predictor of abnormal ER in epilepsy patients ( P = 0.03). During a median follow-up of 7 years, SUDEP occurred in two patients, one with abnormal ER. CONCLUSIONS: Abnormal ER may be more prevalent in epilepsy patients than in controls and is not altered by antiepileptic drugs or achievement of epilepsy suppression. The relation of abnormal ER to SUDEP remains in need of further study.

Critique of the 2017 epileptic seizure and epilepsy classifications.

This article critiques the International League Against Epilepsy (ILAE) 2015-2017 classifications of epilepsy, epileptic seizures, and status epilepticus. It points out the following shortcomings of the ILAE classifications: (1) they mix semiological terms with epileptogenic zone terminology; (2) simple and widely accepted terminology has been replaced by complex terminology containing less information; (3) seizure evolution cannot be described in any detail; (4) in the four-level epilepsy classification, level two (epilepsy category) overlaps almost 100% with diagnostic level one (seizure type); and (5) the design of different classifications with distinct frameworks for newborns, adults, and patients in status epilepticus is confusing. The authors stress the importance of validating the new ILAE classifications and feel that the decision of Epilepsia to accept only manuscripts that use the ILAE classifications is premature and regrettable.

Long-Term Follow-Up of Ictal Asystole in Temporal Lobe Epilepsy: Is Permanent Pacemaker Therapy Needed?

BACKGROUND: Ictal asystole (IA) is an infrequent complication of temporal lobe epilepsy (TLE), but one that may cause transient loss of consciousness (T-LOC) similar to reflex syncope (particularly the vasovagal faint). Although IA-triggered T-LOC is relatively rare, its recognition is therapeutically important. However, while the need for anti-epileptic drugs (AeDs) is broadly accepted, cardiac pacing in IA is controversial. This study aimed to evaluate the need for cardiac pacing in the follow-up of IA patients being treated with AeDs. METHODS AND RESULTS: Six patients (2 men, mean age of 66 ± 16 years), with documented prolonged asystole on electrocardiogram (ECG) in association with TLE, were followed for an average of 19.7 (range, 2-37) years; a pacemaker had been implanted in 4 of 6 patients, whereas 2 patients underwent long-term ECG monitoring with an implantable loop recorder (ILR). The longest documented IA pause lasted 12.6 ± 6.2 (range: 3.5-20) seconds. All patients were treated with AeDs. During follow-up, after optimization of AeD dosing, none of the patients had T-LOC spells or detected epileptic seizure episodes. During regular device interrogation, there was no evidence of pacing interventions (cumulative ventricular pacing, 0%) in the 4 pacemaker patients, and no symptomatic bradyarrhythmias in the 2 ILR patients. CONCLUSIONS: AeD therapy was effective to prevent IA in this cohort of TLE patients with prior IA. Consequently, pacemaker implantation is not immediately indicated for IA prevention, but should be reserved for those cases in which there is documented failure of AeD therapy.

Limbic encephalitis associated with anti-voltage-gated potassium channel complex antibodies as a cause of adult-onset mesial temporal lobe epilepsy.

Recently, some reports have indicated that limbic encephalitis associated with anti-voltage-gated potassium channel complex antibodies (VGKC-Ab) is a cause of adult-onset mesial temporal lobe epilepsy (MTLE). We report a 53-year-old woman who had her first epileptic seizure at the age of 50 years old. Examination by 3-Tesla brain MRI revealed left hippocampal high signal intensity and swelling on fluid-attenuated inversion recovery (FLAIR) and T2-weighted imaging at 2 months after her first seizure. The patient received intravenous methylprednisolone and carbamazepine 300 mg/day. One month later, MRI revealed improvement of her left hippocampal abnormalities. Thereafter, she had no seizures, however, three years after her first seizure, EEG revealed a seizure pattern in the left temporal region. Brain MRI revealed left hippocampal high signal intensity and brain fluorodeoxyglucose positron emission tomography revealed hypermetabolism. Her serum VGKC-Ab levels were 118 pM(normal < 100 pM). Intravenous methylprednisolone therapy was reinitiated. Two months later, her hippocampal abnormalities had improved and 3 months later her VGKC-Ab levels decreased to 4.4 pM. Remission of the epileptic seizures was also observed. This MTLE in the middle age was considered as limbic encephalitis associated with anti- VGKC-Ab. In cases of unexplained adult-onset MTLE, limbic encephalitis associated with anti-VGKC-Ab, which responds well to immunotherapy, should be considered in the differential diagnosis.

[Treatment of epilepsy in the elderly].

As the elderly constitute the most rapidly growing population, epilepsy in this group is an important health issue worldwide. We identified 70 patients who developed epilepsy after the age of 65 years at our institution. Complex partial seizures (CPS) without secondarily generalization were most frequent. The most frequent diagnosis was temporal lobe epilepsy. Etiological diagnosis was possible in nearly 50% patients, including those with cerebrovascular disease. Interictal EEG revealed focal epileptiform discharges in 66.7% of patients. Forty-two patients were on antiepileptic monotherapy and 52 patients had been seizure-free for more than 1 year. Epileptogenecity was relatively low in elderly patients and they responded well to antiepileptic medication.

IgG4-related pachyleptomeningitis with inflammatory pseudotumor.

•We report the first case of IgG4-related pachyleptomeningitis.•Our case showed also an inflammatory pseudotumor on the side ipsilateral to the pachyleptomeningitis.•The pachyleptomeningitis is probably due to inflammation from the dural pseudotumor spreading along the adjacent meninges.

Mesial temporal lobe epilepsy as a neuropsychiatric syndrome of systemic lupus erythematosus.

In this study, we aimed to investigate the types of seizures and epilepsy associated with systemic lupus erythematosus (SLE). We searched the medical records at a tertiary referral center to identify a cohort of epilepsy patients with SLE who were treated between January 2000 and August 2011. We analyzed the clinical and immunologic profiles of these patients, their seizure and epilepsy classifications, electroencephalography (EEG) and magnetic resonance imaging (MRI) assessments, and the treatment administered for epilepsy and SLE. As the result, 17 patients with SLE and epilepsy were identified. Seven patients had mesial temporal lobe epilepsy (MTLE), eight had epilepsy secondary to stroke, and two had generalized epilepsy. Of the seven patients with MTLE, anteriotemporal spikes were noted in all patients with EEG, and MRI findings suggesting hippocampal sclerosis were noted in four patients. Clobazam and levetiracetam were effective in treating three patients, and one patient underwent amygdalohippocampectomy. In conclusion, MTLE may be a characteristic manifestation of neuropsychiatric syndrome of systemic lupus erythematosus.

A more realistic approach, using dynamic stimuli, to test facial emotion recognition impairment in temporal lobe epilepsy.

To explore potentially impaired social functioning in patients with mesial temporal lobe epilepsy (MTLE), we evaluated facial emotion recognition (FER) using dynamic facial stimuli. We evaluated FER in 88 patients with MTLE, including 25 posttemporal lobectomy (PTL) patients, when they watched videos of actors expressing the six basic emotions of happiness, sadness, anger, fear, surprise, and disgust. Thirty-two healthy subjects were examined as controls. The relationships between task, performance, and neurophysiological and radiological variables potentially affecting the ability to recognize moving facial emotions were examined by multivariate analysis. Both the patients with MTLE and the PTL subset demonstrated significantly impaired FER compared with healthy controls. Of the six emotions, they showed impaired recognition of sadness, fear, and disgust. Facial emotion recognition was impaired in patients with chronic MTLE, particularly those with bilateral damage. Failure to recognize emotional expressions, particularly fear, disgust, and sadness, may contribute to difficulties in social functioning and relationship building.

Subclinical tonic-clonic epileptic seizure detected by an implantable loop recorder.

A 73-year old man received an implantable loop recorder (ILR) for the evaluation of transient loss of consciousness (TLOC) spells. His medical history was without any epileptic convulsions or automatism. ILR recording during a spontaneous episode revealed the presence of a regular, narrow QRS complex tachycardia associated with low-amplitude, high-frequency, continuous or discontinuous artifacts, consistent with myopotentials. During the event, the regular, low-amplitude continuous signals gradually became discontinuous, with a prolongation of the inter-signal cycle length, until their disappearance after manual activation of the ILR. The patient was diagnosed as experiencing subclinical tonic-clonic epileptic seizures. Antiepileptic drug treatment was initiated, and the patient has remained free of TLOC symptoms during 13 months follow-up.

[Advances in research on cognitive function related to temporal lobe epilepsy: focus on social cognitive function].

Research on cognitive function related to temporal lobe epilepsy has thus far focused on memory, language, and general intelligence. Recently, however, the concept of social cognitive function has been proposed in the field of neuropsychology. Social cognitive function refers collectively to the higher cognitive functions that are essential in our social lives, and its representative aspects are facial expression recognition and decision-making. Emotional processing centered around the amygdala is thought to play a key role in the neural mechanism of this function. We conducted a study on the social cognitive function (decision-making) of patients with temporal lobe epilepsy, and found that this function is reduced in these patients, and that the right amygdalo-hippocampal complexes play an important role. In order to ensure the best possible treatment for epilepsy patients, it is necessary not only to make an accurate diagnosis and provide appropriate treatment, but also to provide support for enabling a smoother social life from the perspective of social cognitive function. Future research developments in this field are expected to contribute to total management in medical care for epilepsy patients.

[Optimal Use of Perampanel in the Treatment of Patients with Epilepsy Based on the Clinical Evidence and Characteristics].

Perampanel (PER) has been used clinically as monotherapy and adjunctive therapy for focal seizures and as adjunctive therapy for generalized tonic-clonic seizures in epilepsy patients in Japan. In recent years in Japan and worldwide, clinical studies have been conducted on patients with various seizure types of epilepsy. The results have shown that PER has broad spectrum properties. The pooled analysis of controlled trials (PERMIT study) showed PER efficacy in patients with status epilepticus, myoclonic seizures, and absence seizures. In addition, PER has been shown to be safe and effective in patients with juvenile myoclonic epilepsy, Lennox-Gastaut syndrome, and elderly-onset epilepsy that are often difficult to treat with narrow-spectrum ASM. In this review article, we summarize the latest findings on PER, and overview the broad spectrum characteristics of PER. In addition, we discuss the optimal use of PER for patients with epilepsy, focusing on low-dose initiation and on slow titration of PER to minimize adverse events. (Received December 7, 2021; Accepted March 29, 2022; Published July 1, 2022).

Optimal Use of Perampanel in Elderly Asian Patients with Epilepsy: Expert Opinion.

Managing epilepsy in the elderly remains complicated largely due to factors related to aging. In this population, management practices are increasingly shifting towards the use of newer-generation anti-seizure medications (ASMs) as they are generally associated with better tolerability and safety profiles than older ones. Perampanel is a new ASM with broad-spectrum efficacy and a favorable safety profile. However, because of the lack of information and experience in its use, the prescription of perampanel has not been optimized in the elderly in the real-world setting in Asia. A group of epilepsy experts across the region convened at a series of virtual meetings to share their experience and discuss recommendations on perampanel use in elderly patients, including dose optimization, considerations with treatment initiation, and strategies to manage adverse events and maximize tolerability. This article summarizes key clinical and real-world evidence for perampanel in the elderly and consolidates the experts' opinions on optimizing perampanel use in elderly Asian patients with epilepsy, providing practical guidance for clinicians to address challenges related to treatment initiation and tolerance.

Postoperative striatal degeneration: a hitherto unrecognized impact of frontal disconnection surgery for drug-resistant epilepsy. Illustrative cases.

BACKGROUND: Frontal disconnection surgery is a useful surgical option for patients with frontal epilepsy whose seizure onset zones are exceedingly large and thus are not amenable to conventional resective surgery. While it has the advantage of avoiding sequelae stemming from a large resection cavity, the impact of radical anatomofunctional disconnection of such a vast frontal region is not fully understood. OBSERVATIONS: The authors have identified secondary degeneration in the striatum ipsilateral to the frontal disconnection surgery in two adult patients who had otherwise favorable postoperative outcomes following the surgery. On serial postoperative magnetic resonance imaging, the striatum showed transient restricted diffusion in the caudate head and rostral putamen around several weeks postoperatively and subsequent atrophy in the caudate head. The affected striatal regions (i.e., the anterior portion of the striatum) were congruent with the known fronto-striatal connectivity corresponding to the disconnected frontal regions anterior to the primary and supplementary motor areas. Both patients achieved 1-year seizure freedom without apparent disability related to the surgery. LESSONS: The benign postoperative course despite the marked degenerative changes in the ipsilateral striatum supports the feasibility of the frontal disconnection surgery in otherwise inoperable patients with broad frontal epileptogenicity.