Clinical Features and Prognosis in Chinese Patients With Dipeptidyl–Peptidase–Like Protein 6 Antibody–Associated Encephalitis

Objectives:Anti-dipeptidyl–peptidase–like protein 6 (anti-DPPX) encephalitis an extremely rare type of immune-mediated encephalitis. This study aimed to analyze the electroclinical characteristics and prognosis of anti-DPPX encephalitis.Methods:Five patients (all male) with anti-DPPX encephalitis in East China from January 2016 to October 2021 was retrospective analyzed. Electroclinical features and outcomes were reviewed.Results:All five patients were male. The media age at disease onset was 32 years old with a range of 14–56 years. The main symptoms included psychiatric disturbances (2/5), amnesia (4/5), confusion (3/5), and seizures (3/5). Migrating myoclonus were identified in patient 4 with positive DPPX and contactin-associated protein-like 2 antibodies in blood. All of the patients had positive DPPX antibodies in serum. Only one of them had positive antibody in the cerebrospinal fluid. EEG showed diffuse slowing in two patients, but no epileptiform discharges were observed. Eighty percent (4/5) of the patients showed normal brain magnetic resonance imaging. After immunotherapy, improvement of neuropsychiatric symptoms from all of the patients was observed. Over a mean follow-up of 30.8 weeks, all of the patients had marked improvement in the modified Rankin Scale. To date, no tumors were not observed in any patients.Conclusions:Anti-DPPX encephalitis mainly presents as neuropsychiatric symptoms. Cooperation of DPPX antibodies and CASPR2 antibodies might have contributed to the migration of myoclonus in the patient 4. Prompt immunotherapy often results in improvement.

Parkinson's Disease With Visual Hallucinations Is Associated With Epileptiform Activity on EEG

Background: Visual hallucinations (VHs) in Parkinson's disease (PD) are the cardinal symptoms which declare the onset of PD psychosis (PDP). The anthropomorphic and zoomorphic VHs of PD resemble those of Charles Bonnet syndrome and temporal lobe epilepsy. In both of these disorders electroencephalography (EEG) abnormalities have been described. We therefore sought to examine whether VHs in PD were associated with similar EEG abnormalities.Methods: This retrospective observational study searched the medical records of 300 PD patients and filtered for those containing clinical 20-min scalp EEGs. Remaining records were separated into two groups: patients with reported VHs and those without. The prevalence of epileptiform discharges in the EEGs of both groups was identified.Results: Epileptiform discharges were present in 5 of 13 (38.5%) PD patients with VHs; all localized to the temporal lobe. No epileptiform discharges were observed in the EEGs of the 31 PD patients without VHs.Conclusion: The significantly high incidence of temporal lobe epileptiform discharges in PD patients with VHs as compared to those without VHs lends to the possibility of an association visual cortex epileptogenic focus. Accordingly, for treatment-refractory patients, antiepileptic drugs might be considered, as in the case of Charles Bonnet syndrome, temporal lobe epilepsy and migraine with visual aura. Future prospective studies involving larger samples and multi-center cohorts are required to validate these observational findings.

A novel method for multi-scale recording of intracranial EEG through dynamic alteration of electrode surface area

Intracranial EEG (iEEG) plays a critical role in the treatment of neurological diseases, such as epilepsy and Parkinson's disease, as well as the development of neural prostheses and brain computer interfaces. While electrode geometries vary widely across these applications, the impact of electrode size on iEEG features and morphology is not well understood. Some insight has been gained from computer simulation studies and experiments in which signals are recorded using electrodes of different sizes concurrently in different brain regions. Here, we introduce a novel method to record from electrodes of different sizes in the exact same location by changing the size of iEEG electrodes after implantation in the brain. We first present a theoretical model and an in vitro validation of the method. We then report the results of an in vivo implementation in three human subjects with refractory epilepsy. We recorded iEEG data from three different electrode sizes and compared the amplitudes, power spectra, interchannel correlations, and signal-to-noise ratio (SNR) of interictal epileptiform discharges, i.e., epileptic spikes. We found that iEEG amplitude and power decreased as electrode size increased, while inter-channel correlation increased with electrode size. The SNR of epileptic spikes was generally highest in the smallest electrodes, but 39% of spikes had maximal SNR in medium or large electrodes. This likely depends on the precise location and spatial spread of each spike. Overall, this new method enables multi-scale measurements of electrical activity in the human brain that facilitate our understanding of neurophysiology, treatment of neurological disease, and development of novel technologies.

Efficacy and potential predictors of vagus nerve stimulation therapy in refractory postencephalitic epilepsy

Background: Vagus nerve stimulation (VNS) is a therapeutic approach for patients with refractory postencephalitic epilepsy (PEE), which is characterized by drug resistance and disappointing surgical outcomes. However, the efficacy of VNS has not yet been studied in patients with refractory PEE. The present study aimed to demonstrate the efficacy of VNS and evaluate potential clinical predictors in patients with refractory PEE. Methods: We retrospectively collected the outcomes of VNS with at least a 1-year follow-up in all patients with refractory PEE. Subgroups were classified as responders and non-responders according to the efficacy of VNS (⩾50% or < 50% reduction in seizure frequency). Preoperative data were analyzed to screen for potential predictors of VNS responsiveness. Results: A total of 42 refractory PEE patients who underwent VNS therapy were enrolled, with an average age of 21.13 ± 9.70 years. Seizure frequency was reduced by more than 50% in 64.25% of patients, and 7.14% of patients achieved seizure-free events after VNS therapy. In addition, the response rates increased over time, with 40.5%, 50.0% and 57.1%, respectively at 6 months, 12 months, and 24 months after VNS therapy. Preoperative duration of epilepsy, monthly seizure frequency, and spatial distribution of interictal epileptic discharges (IEDs) were correlated with responders ( p < 0.05) in the univariate analysis. Further multivariate regression analysis demonstrated that refractory PEE patients with high monthly seizure frequency or Focal IEDs (focal or multifocal epileptiform discharges) achieved better efficacy on VNS ( p = 0.010, p = 0.003, respectively). Conclusion: VNS is an effective palliative therapy for patients with refractory PEE. Focal IEDs (focal or multifocal epileptiform discharges) and high seizure frequency were potential preoperative predictors of effectiveness after VNS therapy.

The Role of Focal Epilepsy Features in Defining SCN1A Mutation-positive Dravet Syndrome as Generalized and Focal Epilepsy

Background and Purpose: This study was aimed to describe focal epilepsy features of SCN1A mutation-positive Dravet syndrome patients.Methods: A total of 82 SCN1A mutation-positive patients were reviewed retrospectively (39 boys and 43 girls). Seizure type and electroencephalography (EEG) findings were investigated according to the stage, disease onset, and steady state (after age 2 years). Long-term video EEG data were used to classify the seizure type.Results: Focal seizures at onset and the steady state were found in 54.9% (45/82) and 90% (63/70) of patients, respectively. Afebrile focal seizures were an initial seizure in about one fourth of the patients (22/82, 26.8%). Of 48 seizures captured during long-term video EEG monitoring of 30 patients, 19 seizures were classified as focal onset (39.6%). Of the 19 focal seizures, 12 were either focal motor or focal non-motor seizures, and seven were focal onset bilateral tonic-clonic seizure. Focal epileptiform discharges were more frequent than generalized epileptiform discharges at seizure onset and during the clinical course on conventional EEG (3.7% vs. 0%, 52.9% vs. 32.9%, respectively).Conclusions: Our study provides a comprehensive description of focal epilepsy features of SCN1A mutation-positive Dravet syndrome patients. Recognizing these features as defining the clinical spectrum of Dravet syndrome may lead to earlier genetic diagnosis and tailored management.

Assessment of Effective Network Connectivity among MEG None Contaminated Epileptic Transitory Events

Characterizing epileptogenic zones EZ (sources responsible of excessive discharges) would assist a neurologist during epilepsy diagnosis. Locating efficiently these abnormal sources among magnetoencephalography (MEG) biomarker is obtained by several inverse problem techniques. These techniques present different assumptions and particular epileptic network connectivity. Here, we proposed to evaluate performances of distributed inverse problem in defining EZ. First, we applied an advanced technique based on Singular Value Decomposition (SVD) to recover only pure transitory activities (interictal epileptiform discharges). We evaluated our technique’s robustness in separation between transitory and ripples versus frequency range, transitory shapes, and signal to noise ratio on simulated data (depicting both epileptic biomarkers and respecting time series and spectral properties of realistic data). We validated our technique on MEG signal using detector precision on 5 patients. Then, we applied four methods of inverse problem to define cortical areas and neural generators of excessive discharges. We computed network connectivity of each technique. Then, we confronted obtained noninvasive networks to intracerebral EEG transitory network connectivity using nodes in common, connection strength, distance metrics between concordant nodes of MEG and IEEG, and average propagation delay. Coherent Maximum Entropy on the Mean (cMEM) proved a high matching between MEG network connectivity and IEEG based on distance between active sources, followed by Exact low-resolution brain electromagnetic tomography (eLORETA), Dynamical Statistical Parametric Mapping (dSPM), and Minimum norm estimation (MNE). Clinical performance was interesting for entire methods providing in an average of 73.5% of active sources detected in depth and seen in MEG, and vice versa, about 77.15% of active sources were detected from MEG and seen in IEEG. Investigated problem techniques succeed at least in finding one part of seizure onset zone. dSPM and eLORETA depict the highest connection strength among all techniques. Propagation delay varies in this range [18, 25]ms, knowing that eLORETA ensures the lowest propagation delay (18 ms) and the closet one to IEEG propagation delay.

Excess interictal activity marks seizure prone cortical areas and mice in a genetic epilepsy model

Genetic epilepsies are often caused by variants in widely expressed genes, potentially impacting numerous brain regions and functions. For instance, gain-of-function (GOF) variants in the widely expressed Na+-activated K+ channel gene KCNT1 alter basic neurophysiological and synaptic properties of cortical neurons, leading to developmental epileptic encephalopathy. Yet, aside from causing seizures, little is known about how such variants reshape interictal brain activity, and how this relates to epileptic activity and other disease symptoms. To address this knowledge gap, we monitored neural activity across the dorsal cortex in a mouse model of human KCNT1-related epilepsy using in vivo, awake widefield Ca2+ imaging. We observed 52 spontaneous seizures and 1700 interictal epileptiform discharges (IEDs) in homozygous mutant (Kcnt1m/m) mice, allowing us to map their appearance and spread at high spatial resolution. Outside of seizures and IEDs, we detected ~46,000 events, representing interictal cortical activity, in both Kcnt1m/m and wild-type (WT) mice, and we classified them according to their spatial profiles. Spontaneous seizures and IEDs emerged within a consistent set of susceptible cortical areas, and seizures propagated both contiguously and non-contiguously within these areas in a manner influenced, but not fully determined, by underlying synaptic connectivity. Seizure emergence was predicted by a progressive concentration of total cortical activity within the impending seizure emergence zone. Outside of seizures and IEDs, similar events were detected in WT and Kcnt1m/m mice, suggesting that the spatial structure of interictal activity was largely preserved. Several features of these events, however, were altered in Kcnt1m/m mice. Most event types were briefer, and their intensity more variable, across Kcnt1m/m mice; mice showing more intense activity spent more time in seizure. Furthermore, the rate of events whose spatial profile overlapped with where seizures and IEDs emerged was increased in Kcnt1m/m mice. Taken together, these results demonstrate that an epilepsy-causing K+ channel variant broadly alters physiology. Yet, outside of seizures and IEDs, it acts not to produce novel types of cortical activity, but rather to modulate its amount. The areas where seizures and IEDs emerge show excessively frequent and intense interictal activity and the mean intensity of an individual's cortical activity predicts its seizure burden. These findings provide critical guidance for targeting future research and therapy development.

Isolated Memory Loss in Anti-NMDAR Encephalitis

Background and ObjectivesTo report a case of anti-NMDAR encephalitis presenting with isolated memory dysfunction.MethodsA 29-year-old woman was admitted to the Neurology Department referring memory impairment with a subacute onset. The initial assessment included EEG, neuropsychological tests, and brain MRI. Serum and CSF samples were collected for immunologic studies. The diagnostic evaluation was completed with a total body PET scan.ResultsPatient's neurologic examination was unremarkable apart from an episodic memory deficit, confirmed by neuropsychological examination. The EEG revealed epileptiform discharges in the temporal lobes, whereas brain MRI showed bilateral temporal lobes hyperintense lesions on fluid-attenuated inversion recovery images and T2-weighted images. NMDAR-IgG was detected in the patient's serum and CSF by cell-based assay confirming the diagnosis of definite anti-NMDAR encephalitis. The total body PET showed only a slight hypometabolism in the right temporal cortex and in the cerebellar hemispheres. After a course of IV immunoglobulin and corticosteroid therapy, a marked improvement of the memory deficit was observed.DiscussionThis case shows that anti-NMDAR encephalitis can present with isolated memory loss. Neural antibody testing in these patients could play a pivotal role in early diagnosis and prompt treatment.

Research Progress on the Effect of Epilepsy and Antiseizure Medications on PCOS Through HPO Axis

Epilepsy is a common chronic neurological disease that manifests as recurrent seizures. The incidence and prevalence of epilepsy in women are slightly lower than those in men. Polycystic ovary syndrome (PCOS), a reproductive endocrine system disease, is a complication that women with epilepsy are susceptible to, and its total prevalence is 8%–13% in the female population and sometimes as high as 26% in female epilepsy patients. The rate of PCOS increased markedly in female patients who chose valproate (VPA), to 1.95 times higher than that of other drugs. In addition, patients receiving other anti-seizure medications (ASMs), such as lamotrigine (LTG), oxcarbazepine (OXC), and carbamazepine (CBZ), also have reproductive endocrine abnormalities. Some scholars believe that the increase in incidence is related not only to epilepsy itself but also to ASMs. Epileptiform discharges can affect the activity of the pulse generator and then interfere with the reproductive endocrine system by breaking the balance of the hypothalamic–pituitary–ovarian (HPO) axis. ASMs may also cause PCOS-like disorders of the reproductive endocrine system through the HPO axis. Moreover, other factors such as hormone metabolism and related signalling pathways also play a role in it.

Temporal Lobe Spikes Affect Distant Intrinsic Connectivity Networks

Objective: To evaluate local and distant blood oxygen level dependent (BOLD) signal changes related to interictal epileptiform discharges (IED) in drug-resistant temporal lobe epilepsy (TLE).Methods: Thirty-three TLE patients undergoing EEG–functional Magnetic Resonance Imaging (fMRI) as part of the presurgical workup were consecutively enrolled. First, a single-subject spike-related analysis was performed: (a) to verify the BOLD concordance with the presumed Epileptogenic Zone (EZ); and (b) to investigate the Intrinsic Connectivity Networks (ICN) involvement. Then, a group analysis was performed to search for common BOLD changes in TLE.Results: Interictal epileptiform discharges were recorded in 25 patients and in 19 (58%), a BOLD response was obtained at the single-subject level. In 42% of the cases, BOLD changes were observed in the temporal lobe, although only one patient had a pure concordant finding, with a single fMRI cluster overlapping (and limited to) the EZ identified by anatomo-electro-clinical correlations. In the remaining 58% of the cases, BOLD responses were localized outside the temporal lobe and the presumed EZ. In every patient, with a spike-related fMRI map, at least one ICN appeared to be involved. Four main ICNs were preferentially involved, namely, motor, visual, auditory/motor speech, and the default mode network. At the single-subject level, EEG–fMRI proved to have high specificity (above 65%) in detecting engagement of an ICN and the corresponding ictal/postictal symptom, and good positive predictive value (above 67%) in all networks except the visual one. Finally, in the group analysis of BOLD changes related to IED revealed common activations at the right precentral gyrus, supplementary motor area, and middle cingulate gyrus.Significance: Interictal temporal spikes affect several distant extra-temporal areas, and specifically the motor/premotor cortex. EEG–fMRI in patients with TLE eligible for surgery is recommended not for strictly localizing purposes rather it might be useful to investigate ICNs alterations at the single-subject level.