Temporal lobe volume predicts Wada memory test performance in patients with mesial temporal sclerosis
Dynamin 1 (DNM1) is a large guanosine triphosphatase involved in clathrin-mediated endocytosis. In recent studies, de novo mutations in DNM1 have been identified in five individuals with epileptic encephalopathy. In this study, we report two patients with early onset epileptic encephalopathy possessing de novo DNM1 mutations. Using whole exome sequencing, we detected the novel mutation c.127G>A (p.Gly43Ser) in a patient with Lennox-Gastaut syndrome, and a recurrent mutation c.709C>T (p.Arg237Trp) in a patient with West syndrome. Structural consideration of DNM1 mutations revealed that both mutations would destabilize the G domain structure and impair nucleotide binding, dimer formation, and/or GTPase activity of the G domain. These and previous cases of DNM1 mutations were reviewed to verify the phenotypic spectrum. The main clinical features of DNM1 mutations include intractable seizures, intellectual disability, developmental delay, and hypotonia. Most cases showed development delay before the onset of seizures. A patient carrying p.Arg237Trp in this report showed a different developmental status from that of a previously reported case, together with characteristic extrapyramidal movement.
Ictal onset patterns of local field potentials, high frequency oscillations, and unit activity in human mesial temporal lobe epilepsy
To characterize local field potentials, high frequency oscillations, and single unit firing patterns in microelectrode recordings of human limbic onset seizures.Methods
Wide bandwidth local field potential recordings were acquired from microelectrodes implanted in mesial temporal structures during spontaneous seizures from six patients with mesial temporal lobe epilepsy.Results
In the seizure onset zone, distinct epileptiform discharges were evident in the local field potential prior to the time of seizure onset in the intracranial EEG. In all three seizures with hypersynchronous (HYP) seizure onset, fast ripples with incrementally increasing power accompanied epileptiform discharges during the transition to the ictal state (p < 0.01). In a single low voltage fast (LVF) onset seizure a triad of evolving HYP LFP discharges, increased single unit activity, and fast ripples of incrementally increasing power were identified ~20 s prior to seizure onset (p < 0.01). In addition, incrementally increasing fast ripples occurred after seizure onset just prior to the transition to LVF activity (p < 0.01). HYP onset was associated with an increase in fast ripple and ripple rate (p < 0.05) and commonly each HYP discharge had a superimposed ripple followed by a fast ripple. Putative excitatory and inhibitory single units could be distinguished during limbic seizure onset, and heterogeneous shifts in firing rate were observed during LVF activity.Significance
Epileptiform activity is detected by microelectrodes before it is detected by depth macroelectrodes, and the one clinically identified LVF ictal onset was a HYP onset at the local level. Patterns of incrementally increasing fast ripple power are consistent with observations in rats with experimental hippocampal epilepsy, suggesting that limbic seizures arise when small clusters of synchronously bursting neurons increase in size, coalesce, and reach a critical mass for propagation.
Mining continuous intracranial EEG in focal canine epilepsy: Relating interictal bursts to seizure onsets
Brain regions are localized for resection during epilepsy surgery based on rare seizures observed during a short period of intracranial electroencephalography (iEEG) monitoring. Interictal epileptiform bursts, which are more prevalent than seizures, may provide complementary information to aid in epilepsy evaluation. In this study, we leverage a long-term iEEG dataset from canines with naturally occurring epilepsy to investigate interictal bursts and their electrographic relationship to seizures.Methods
Four dogs were included in this study, each monitored previously with continuous iEEG for periods of 475.7, 329.9, 45.8, and 451.8 days, respectively, for a total of >11,000 h. Seizures and bursts were detected and validated by two board-certified epileptologists. A published Bayesian model was applied to analyze the dynamics of interictal epileptic bursts on EEG and compare them to seizures.Results
In three dogs, bursts were stereotyped and found to be statistically similar to periods before or near seizure onsets. Seizures from one dog during status epilepticus were markedly different from other seizures in terms of burst similarity.Significance
Shorter epileptic bursts explored in this work have the potential to yield significant information about the distribution of epileptic events. In our data, bursts are at least an order of magnitude more prevalent than seizures and occur much more regularly. Our finding that bursts often display pronounced similarity to seizure onsets suggests that they contain relevant information about the epileptic networks from which they arise and may aide in the clinical evaluation of epilepsy in patients.
Research suggests that individuals with chronic epilepsy display differences in their self-identity. The mechanisms by which self-identity is altered, however, are not well understood. Neural networks supporting autobiographical memory retrieval in the mesial temporal (MT) lobe are thought to be fundamental to self-identity processes. Thus, we examined differences in self-identity and autobiographical memory in patients with either MT or non–mesial temporal (NMT) foci with early or late age of habitual seizure onset.Methods
Participants included 102 adults: 51 healthy individuals and 51 patients with drug-resistant focal seizures (19 MT, 32 NMT). We used the Ego Identity Process Questionnaire to profile the identity development of participants, and examined how this related to memory function assessed using the Autobiographical Memory Test.Results
Patients and controls had strikingly different self-identity profiles, with early onset MT patients showing the least identity development compared to controls and other patient groups. In contrast, late-onset NMT patients showed the highest level of identity development of the patient groups and closely resembled healthy controls (p < 0.05 for all comparisons). For all MT patients, poor autobiographical memory retrieval was correlated with altered self-identity (p < 0.001). No associations between autobiographical memory and self-identity were evident in the NMT group.Significance
Self-identity in epilepsy may be modulated by the extent to which seizure foci impinge on the autobiographical memory network and the timing of seizure onset. Early disruption to MT regions of the autobiographical memory network may constitute a neurocognitive mechanism by which self-identity is altered in chronic focal epilepsy.
We aimed to explore the patterns of health-related behaviors (HRBs) such as smoking and physical activity in people with epilepsy in the community and examine whether behaviors have changed over the past decade.Methods
We conducted a repeated cross-sectional study using data from a series of five cycles (2001–2011) of the Canadian Community Health Survey, a national population-based survey. The proportions and odds ratios with 95% confidence intervals for HRBs and comorbidities in people with epilepsy (PWE) compared to respondents without epilepsy were calculated for each survey over the 10-year period, and estimates were examined for changes over time.Results
The study included 522,722 participants of whom 3,220 (0.6%) had epilepsy. The proportion of PWE who did not participate in physical activity decreased over time (2001 = 17.2%, 2010/2011 = 8.5%), as did the proportion of PWE who smoked cigarettes (2001 = 32.3%, 2010/2011 = 18.0%). PWE had consistently reduced alcohol consumption in comparison to the general population. Fewer than half of participants met the recommended daily guidelines for fruit and vegetable consumption. An apparent reduction in the prevalence of heart disease occurred in PWE (2001 = 11.7%, 2010/2011 = 4.0%), but not in people without epilepsy; however, similar trends were not observed for other cardiovascular comorbidities studied.Significance
Apparent improvements in smoking cessation and physical activity occurred in PWE. Despite these improvements, physicians should continue to counsel their patients on the importance of healthy lifestyle choices. Further exploration into the reasons for the apparent decrease in the prevalence of heart disease in PWE is warranted.
Postencephalitic epilepsy and drug-resistant epilepsy after infectious and antibody-associated encephalitis in childhood: Clinical and etiologic risk factors
To define the risk factors for postencephalitic epilepsy (PE) and drug-resistant epilepsy (DRE) in childhood following infectious and autoimmune encephalitis, we included 147 acute encephalitis patients with a median follow-up of 7.3 years (range 2–15.8 years). PE was defined as the use of antiepileptic drugs (AEDs) for ≥24 months, and DRE was defined as the persistence of seizures despite ≥2 appropriate AEDs at final follow-up. PE and DRE were diagnosed in 31 (21%) and 15 (10%) of patients, respectively. The features during acute encephalitis predictive of DRE (presented as odds ratio [OR] with confidence intervals [CIs]) were status epilepticus (OR 10.8, CI 3.4–34.3), visual disturbance (6.4, 1.4–29.9), focal seizures (6.2, 1.9–20.6), magnetic resonance imaging (MRI) hippocampal/amygdala involvement (5.0, 1.7–15.4), intensive care admission (4.7, 1.4–15.4), use of >3 AEDs (4.5, 1.2–16.1), MRI gadolinium enhancement (4.1, 1.2–14.2), any seizure (3.9, 1.1–14.4), and electroencephalography (EEG) epileptiform discharges (3.9, 1.3–12.0). On multivariable regression analysis, only status epilepticus remained predictive of DRE in all models. DRE was common in herpes simplex virus (3/9, 33%) and unknown (8/40, 20%) encephalitis, but absent in acute disseminated encephalomyelitis (ADEM) (0/32, 0%), enterovirus (0/18), and anti-N-methyl-d-aspartate receptor–NMDAR encephalitis (0/9). We have identified risk factors for DRE and demonstrated “high-risk,” and “low-risk” etiologies.
Laryngeal motility alteration: A missing link between sleep apnea and vagus nerve stimulation for epilepsy
This study aimed to evaluate the prevalence and the relationship of sleep breathing disorders (SBDs) and laryngeal motility alterations in patients with drug-resistant epilepsy after vagus nerve stimulator (VNS) implantation. Twenty-three consecutive patients with medically refractory epilepsy underwent out-of-center sleep testing before and after VNS implantation. Eighteen eligible subjects underwent endoscopic laryngeal examination post-VNS implantation. Statistical analysis was carried out to assess an association between laryngeal motility alterations and the onset/worsening of SBDs. After VNS implantation, 11 patients showed a new-onset mild/moderate SBD. Half of the patients already affected by obstructive sleep apnea (OSA) showed worsening of SBD. All of the patients with a new-onset OSA had a laryngeal pattern with left vocal cord adduction (LVCA) during VNS stimulation. The association between VNS-induced LVCA and SBD was statistically significant. This study suggests an association between VNS and SBD, hinting to a pivotal role of laryngeal motility alterations. The relationship between SBD and VNS-induced LVCA supports the need to routinely investigate sleep respiratory and laryngeal motility patterns before and after VNS implantation.