Semiological classification of psychogenic nonepileptic seizures.

PURPOSE: We classified patients with psychogenic nonepileptic seizures (PNESs) according to a newly proposed classification system. Then, we investigated the demographic and clinical differences between various classes of the patients. METHODS: We retrospectively investigated all patients with PNESs admitted to the Jefferson Comprehensive Epilepsy Center from 2012 through 2016. We classified the patients into four distinct classes: patients with generalized motor seizures, patients with akinetic seizures, patients with focal motor seizures, and patients with seizures with subjective symptoms. All patients were interviewed by a neuropsychologist and were administered psychological assessment measures, including questions about PNES risk factors. For the statistical analyses, we compared patients who had generalized motor seizures with patients who had nonmotor seizures. RESULTS: Sixty-three patients were studied. Thirty-five (55.6%) patients had generalized motor seizures, 14 (22.2%) had seizures with subjective symptoms, 12 (19%) had akinetic seizures, and two (3.2%) patients had focal motor seizures. Patients with generalized motor seizures (35 patients) demonstrated a trend for later age at onset (p=0.06), more frequently had a history of substance abuse (p=0.001), and more often had loss of responsiveness with their seizures (p=0.04) compared with patients who had nonmotor seizures (26 patients). CONCLUSION: The recently proposed PNES classification system is useful and practical. This proposed classification of PNESs may address proper diagnosis and provide standardization across future studies. This may also potentially shed light on the etiologic understanding and management of various classes of patients affected with PNESs

Attention-deficit/hyperactivity disorder medication and seizures

OBJECTIVE: Individuals with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of seizures, but there is uncertainty about whether ADHD medication treatment increases risk among patients with and without preexisting seizures. METHODS: We followed a sample of 801,838 patients with ADHD who had prescribed drug claims from the Truven Health MarketScan Commercial Claims and Encounters databases to examine whether ADHD medication increases the likelihood of seizures among ADHD patients with and without a history of seizures. First, we assessed overall risk of seizures among patients with ADHD. Second, within-individual concurrent analyses assessed odds of seizure events during months when a patient with ADHD received ADHD medication compared with when the same individual did not, while adjusting for antiepileptic medications. Third, within-individual long-term analyses examined odds of seizure events in relation to the duration of months over the previous 2 years patients received medication. RESULTS: Patients with ADHD were at higher odds for any seizure compared with non-ADHD controls (odds ratio [OR] = 2.33, 95% confidence interval [CI] = 2.24-2.42 males; OR = 2.31, 95% CI = 2.22-2.42 females). In adjusted within-individual comparisons, ADHD medication was associated with lower odds of seizures among patients with (OR = 0.71, 95% CI = 0.60-0.85) and without (OR = 0.71, 95% CI = 0.62-0.82) prior seizures. Long-term within-individual comparisons suggested no evidence of an association between medication use and seizures among individuals with (OR = 0.87, 95% CI = 0.59-1.30) and without (OR = 1.01, 95% CI = 0.80-1.28) a seizure history. CONCLUSIONS: Results reaffirm that patients with ADHD are at higher risk of seizures. However, ADHD medication was associated with lower risk of seizures within individuals while they were dispensed medication, which is not consistent with the hypothesis that ADHD medication increases risk of seizures

The importance of early immunotherapy in patients with faciobrachial dystonic seizures.

Faciobrachial dystonic seizures and limbic encephalitis closely associate with antibodies to leucine-rich glioma-inactivated 1 (LGI1). Here, we describe 103 consecutive patients with faciobrachial dystonic seizures and LGI1 antibodies to understand clinical, therapeutic and serological differences between those with and without cognitive impairment, and to determine whether cessation of faciobrachial dystonic seizures can prevent cognitive impairment. The 22/103 patients without cognitive impairment typically had normal brain MRI, EEGs and serum sodium levels (P < 0.0001). Overall, cessation of faciobrachial dystonic seizures with antiepileptic drugs alone occurred in only 9/89 (10%) patients. By contrast, 51% showed cessation of faciobrachial dystonic seizures 30 days after addition of immunotherapy (P < 0.0001), with earlier cessation in cognitively normal patients (P = 0.038). Indeed, expedited immunotherapy (P = 0.031) and normal cognition (P = 0.0014) also predicted reduced disability at 24 months. Furthermore, of 80 patients with faciobrachial dystonic seizures as their initial feature, 56% developed cognitive impairment after 90 days of active faciobrachial dystonic seizures. Whereas only one patient developed cognitive impairment after cessation of faciobrachial dystonic seizures (P < 0.0001). All patients had IgG4-LGI1 antibodies, but those with cognitive impairment had higher proportions of complement-fixing IgG1 antibodies (P = 0.03). Both subclasses caused LGI1-ADAM22 complex internalization, a potential non-inflammatory epileptogenic mechanism. In summary, faciobrachial dystonic seizures show striking time-sensitive responses to immunotherapy, and their cessation can prevent the development of cognitive impairment.awx323media15681705685001

Audiogenic reflex seizures in cats

This study aims at characterizing feline audiogenic reflex seizures (FARS). An online questionnaire was developed to capture information from owners with cats suffering FARS. This was collated with the medical records from the primary veterinarian. Ninety-six cats were included. Myoclonic seizures were one of the cardinal signs of this syndrome (90/96), frequently occurring prior to generalized tonic-clonic seizures (GTCS) in this population. Other features include a late-onset (median 15 years) and absence seizures (6/96), with most seizures triggered by high frequency sounds amid occasional spontaneous seizures (up to 20%). Half the population (48/96) had hearing impairment or were deaf. One third of cats (35/96) had concurrent diseases, most likely reflecting the age distribution. Birmans were strongly represented (30/96). Levetiracetam gave good seizure control. The course of the epilepsy was non-progressive in the majority (68/96) with an improvement over time in some (23/96). Only 33/96 and 11/90 owners respectively felt the GTCS and myoclonic seizures affected their cat’s quality of life (QoL). Despite this, many owners (50/96) reported a slow decline in their cat’s health becoming less responsive (43/50), not jumping (41/50), uncoordinated or weak in the pelvic limbs (24/50), and exhibiting dramatic weight loss (39/50). These signs were exclusively reported in cats experiencing seizures for >2 years with 42/50 owners stating these signs affected their cat’s QoL. In gathering data on audiogenic seizures in cats, we have identified a new epilepsy syndrome named FARS with a geriatric-onset. Further studies are warranted to investigate potential genetic predispositions to this condition

One-shot Learning for iEEG Seizure Detection Using End-to-end Binary Operations: Local Binary Patterns with Hyperdimensional Computing

This paper presents an efficient binarized algorithm for both learning and classification of human epileptic seizures from intracranial electroencephalography (iEEG). The algorithm combines local binary patterns with brain-inspired hyperdimensional computing to enable end-to-end learning and inference with binary operations. The algorithm first transforms iEEG time series from each electrode into local binary pattern codes. Then atomic high-dimensional binary vectors are used to construct composite representations of seizures across all electrodes. For the majority of our patients (10 out of 16), the algorithm quickly learns from one or two seizures (i.e., one-/few-shot learning) and perfectly generalizes on 27 further seizures. For other patients, the algorithm requires three to six seizures for learning. Overall, our algorithm surpasses the state-of-the-art methods for detecting 65 novel seizures with higher specificity and sensitivity, and lower memory footprint.Comment: Published as a conference paper at the IEEE BioCAS 201

Postictal serotonin levels are associated with peri-ictal apnea.

ObjectiveTo determine the relationship between serum serotonin (5-HT) levels, ictal central apnea (ICA), and postconvulsive central apnea (PCCA) in epileptic seizures.MethodsWe prospectively evaluated video EEG, plethysmography, capillary oxygen saturation (SpO2), and ECG for 49 patients (49 seizures) enrolled in a multicenter study of sudden unexpected death in epilepsy (SUDEP). Postictal and interictal venous blood samples were collected after a clinical seizure for measurement of serum 5-HT levels. Seizures were classified according to the International League Against Epilepsy 2017 seizure classification. We analyzed seizures with and without ICA (n = 49) and generalized convulsive seizures (GCS) with and without PCCA (n = 27).ResultsPostictal serum 5-HT levels were increased over interictal levels for seizures without ICA (p = 0.01), compared to seizures with ICA (p = 0.21). In patients with GCS without PCCA, serum 5-HT levels were increased postictally compared to interictal levels (p < 0.001), but not in patients with seizures with PCCA (p = 0.22). Postictal minus interictal 5-HT levels also differed between the 2 groups with and without PCCA (p = 0.03). Increased heart rate was accompanied by increased serum 5-HT levels (postictal minus interictal) after seizures without PCCA (p = 0.03) compared to those with PCCA (p = 0.42).ConclusionsThe data suggest that significant seizure-related increases in serum 5-HT levels are associated with a lower incidence of seizure-related breathing dysfunction, and may reflect physiologic changes that confer a protective effect against deleterious phenomena leading to SUDEP. These results need to be confirmed with a larger sample size study

p53-sensitive epileptic behavior and inflammation in Ft1 hypomorphic mice

Epilepsy is a complex clinical condition characterized by repeated spontaneous seizures. Seizures have been linked to multiple drivers including DNA damage accumulation. Investigation of epilepsy physiopathology in humans imposes ethical and practical limitations, for this reason model systems are mostly preferred. Among animal models, mouse mutants are particularly valuable since they allow conjoint behavioral, organismal, and genetic analyses. Along with this, since aging has been associated with higher frequency of seizures, prematurely aging mice, simulating human progeroid diseases, offer a further useful modeling element as they recapitulate aging over a short time-window. Here we report on a mouse mutant with progeroid traits that displays repeated spontaneous seizures. Mutant mice were produced by reducing the expression of the gene Ft1 (AKTIP in humans). In vitro, AKTIP/Ft1 depletion causes telomere aberrations, DNA damage, and cell senescence. AKTIP/Ft1 interacts with lamins, which control nuclear architecture and DNA function. Premature aging defects of Ft1 mutant mice include skeletal alterations and lipodystrophy. The epileptic behavior of Ft1 mutant animals was age and sex linked. Seizures were observed in 18 mutant mice (23.6% of aged ≥ 21 weeks), at an average frequency of 2.33 events/mouse. Time distribution of seizures indicated non-random enrichment of seizures over the follow-up period, with 75% of seizures happening in consecutive weeks. The analysis of epileptic brains did not reveal overt brain morphological alterations or severe neurodegeneration, however, Ft1 reduction induced expression of the inflammatory markers IL-6 and TGF-β. Importantly, Ft1 mutant mice with concomitant genetic reduction of the guardian of the genome, p53, showed no seizures or inflammatory marker activation, implicating the DNA damage response into these phenotypes. This work adds insights into the connection among DNA damage, brain function, and aging. In addition, it further underscores the importance of model organisms for studying specific phenotypes, along with permitting the analysis of genetic interactions at the organismal level