Autoimmune seizures and epilepsy Geis, Christian; Planagumà, Jesus; Carreño, Mar ...
The Journal of clinical investigation,
03/2019, Letnik:
129, Številka:
3
Journal Article
Recenzirano
Odprti dostop
The rapid expansion in the number of encephalitis disorders associated with autoantibodies against neuronal proteins has led to an incremental increase in use of the term "autoimmune epilepsy," yet ...has occurred with limited attention to the physiopathology of each disease and genuine propensity to develop epilepsy. Indeed, most autoimmune encephalitides present with seizures, but the probability of evolving to epilepsy is relatively small. The risk of epilepsy is higher for disorders in which the antigens are intracellular (often T cell-mediated) compared with disorders in which the antigens are on the cell surface (antibody-mediated). Most autoantibodies against neuronal surface antigens show robust effects on the target proteins, resulting in hyperexcitability and impairment of synaptic function and plasticity. Here, we trace the evolution of the concept of autoimmune epilepsy and examine common inflammatory pathways that might lead to epilepsy. Then, we focus on several antibody-mediated encephalitis disorders that associate with seizures and review the synaptic alterations caused by patients' antibodies, with emphasis on those that have been modeled in animals (e.g., antibodies against NMDA, AMPA receptors, LGI1 protein) or in cultured neurons (e.g., antibodies against the GABAb receptor).
Glutamic acid decarboxylase 65 antibodies (anti-GAD65) have been found in patients with late-onset chronic temporal lobe epilepsy (TLE). No prior neuroimaging studies have addressed how they affect ...hippocampal volume and shape and how they relate to cognitive abnormalities. We aimed to investigate both brain structure and function in patients with isolated TLE and high anti-GAD65 levels (RIA ≥ 2000 U/ml) compared to 8 non-immune mesial TLE (niTLE) and 8 healthy controls (HC). Hippocampal subfield volume properties were correlated with the duration of the disease and cognitive test scores. The affected hippocampus of GAD-TLE patients showed no volume changes to matched HC whereas niTLE volumes were significantly smaller. Epilepsy duration in GAD-TLE patients correlated negatively with volumes in the presubiculum, subiculum, CA1, CA2-3, CA4, molecular layer and granule cell-molecular layer of the dentate nucleus. We found differences by advanced vertex-wise shape analysis in the anterior hippocampus of the left GAD-TLE compared to HC whereas left niTLE showed bilateral posterior hippocampus deformation. Verbal deficits were similar in GAD-TLE and niTLE but did not correlate to volume changes. These data might suggest a distinct expression of hippocampal structural and functional abnormalities based on the immune response.
Background
Lockdown due to the SARS‐CoV‐2 pandemic became a challenge to maintain care for patients with epilepsy; we aimed to find out how the pandemic affected them.
Methods
We sent an online ...22‐item questionnaire to patients from our outpatient clinic, a reference centre in Spain for drug‐resistant epilepsy, inquiring about the effects of lockdown, from March to May 2020.
Results
We sent the survey to 627 patients; 312 (58% women) sent a complete response and were included. Of all respondents, 57% took >2 antiseizure medications. One‐third of respondents (29%) declared an associated cognitive or motor disability. A minority had confirmed infection with SARS‐CoV‐2 (1.92%). Seizure frequency remained like usual in 56% of patients, while 31.2% reported an increase. Less than 10% needed emergent assistance. Almost half reported anxiety or depression, and 25% increased behavioural disorders. Mood (F: 5.40; p: 0.002) and sleep disorders (F = 2.67; p: 0.05) were associated with increase in seizure frequency. Patients were able to contact their physicians when needed and were open to a future telematic approach to follow‐up visits.
Conclusions
Seizure frequency and severity remained unchanged in most patients during the lockdown. Mood and sleep disorders were common and associated with seizure worsening. Patients were open to telematic care in the future.
Psychogenic non-epileptic seizures (PNES) are complex clinical manifestations and misdiagnosis as status epilepticus remains high, entailing deleterious consequences for patients. ...Video-electroencephalography (vEEG) remains the gold-standard method for diagnosing PNES. However, time and economic constraints limit access to vEEG, and clinicians lack fast and reliable screening tools to assist in the differential diagnosis with epileptic seizures (ES). This study aimed to design and validate the PNES-DSC, a clinically based PNES diagnostic suspicion checklist with adequate sensitivity (Se) and specificity (Sp) to discriminate PNES from ES.
A cross-sectional study with 125 patients (n = 104 drug-resistant epilepsy; n = 21 PNES) admitted for a vEEG protocolised study of seizures. A preliminary PNES-DSC (16-item) was designed and used by expert raters blinded to the definitive diagnosis to evaluate the seizure video recordings for each patient. Cohen's kappa coefficient, leave-one-out cross-validation (LOOCV) and balance accuracy (BAC) comprised the main validation analysis.
The final PNES-DSC is a 6-item checklist that requires only two to be present to confirm the suspicion of PNES. The LOOCV showed 71.4% BAC (Se = 45.2%; Sp = 97.6%) when the expert rater watched one seizure video recording and 83.4% BAC (Se = 69.6%; Sp = 97.2%) when the expert rater watched two seizure video recordings.
The PNES-DSC is a straightforward checklist with adequate psychometric properties. With an integrative approach and appropriate patient history, the PNES-DSC can assist clinicians in expediting the final diagnosis of PNES when vEEG is limited. The PNES-DSC can also be used in the absence of patients, allowing clinicians to assess seizure recordings from smartphones.
•Misdiagnosis of psychogenic non-epileptic seizures (PNES) remains high.•The PNES-DSC is a 6-item clinically based PNES diagnostic suspicion checklist.•The PNES-DSC has adequate power to discriminate PNES from epileptic seizures.•The PNES-DSC has 71.4% accuracy (Se = 45.2%; Sp = 97.6%) in confirming suspicion of PNES after one seizure.•The PNES-DSC has 83.4% accuracy (Se = 69.6%; Sp = 97.2%) in confirming suspicion of PNES after two seizures.
Cognitive‐relevant information is processed by different brain areas that cooperate to eventually produce a response. The relationship between local activity and global brain states during such ...processes, however, remains for the most part unexplored. To address this question, we designed a simple face‐recognition task performed in patients with drug‐resistant epilepsy and monitored with intracranial electroencephalography (EEG). Based on our observations, we developed a novel analytical framework (named “local–global” framework) to statistically correlate the brain activity in every recorded gray‐matter region with the widespread connectivity fluctuations as proxy to identify concurrent local activations and global brain phenomena that may plausibly reflect a common functional network during cognition. The application of the local–global framework to the data from three subjects showed that similar connectivity fluctuations found across patients were mainly coupled to the local activity of brain areas involved in face information processing. In particular, our findings provide preliminary evidence that the reported global measures might be a novel signature of functional brain activity reorganization when a stimulus is processed in a task context regardless of the specific recorded areas.
Cognitive‐relevant information is processed by different brain areas that cooperate to eventually produce a response. Here, we develop a novel analytical framework (named “local–global” framework) to statistically correlate the signal power in every recorded gray‐matter region (intracranial electroencephalography) with the widespread connectivity fluctuations as proxy to identify concurrent local and global activity that may plausibly reflect a common functional network during cognition. The application of the local–global framework to the data from three subjects with different recorded areas showed similar connectivity fluctuations, which were mainly coupled to local activity of brain areas involved in the task.
Computational models and in vivo studies in rodents suggest that the emergence of gamma activity (40–140 Hz) during memory encoding and retrieval is coupled to opposed-phase states of the underlying ...hippocampal theta rhythm (4–9 Hz).1,2,3,4,5,6,7,8,9,10 However, direct evidence for whether human hippocampal gamma-modulated oscillatory activity in memory processes is coupled to opposed-phase states of the ongoing theta rhythm remains elusive. Here, we recorded local field potentials (LFPs) directly from the hippocampus of 10 patients with epilepsy, using depth electrodes. We used a memory encoding and retrieval task whereby trial unique sequences of pictures depicting real-life episodes were presented, and 24 h later, participants were asked to recall them upon the appearance of the first picture of the encoded episodic sequence. We found theta-to-gamma cross-frequency coupling that was specific to the hippocampus during both the encoding and retrieval of episodic memories. We also revealed that gamma was coupled to opposing theta phases during both encoding and recall processes. Additionally, we observed that the degree of theta-gamma phase opposition between encoding and recall was associated with participants’ memory performance, so gamma power was modulated by theta phase for both remembered and forgotten trials, although only for remembered trials the dominant theta phase was different for encoding and recall trials. The current results offer direct empirical evidence in support of hippocampal theta-gamma phase opposition models in human long-term memory and provide fundamental insights into mechanistic predictions derived from computational and animal work, thereby contributing to establishing similarities and differences across species.
•Hippocampal phase-amplitude coupling modulates memory in humans•Phase preference of encoding and recall are opposed•Theta-gamma opposition predicts memory performance
Saint Amour di Chanaz et al. find evidence that hippocampal gamma is coupled to opposing theta phases during the encoding and retrieval of episodic memories. These results provide support for the memory models that involve hippocampal theta-gamma phase opposition and offer insight into similarities and differences between species.
Sleep-Related Epilepsy Carreño, Mar; Fernández, Santiago
Current treatment options in neurology,
05/2016, Letnik:
18, Številka:
5
Journal Article
Recenzirano
Opinion statement
Sleep has a strong influence on interictal epileptiform discharges and on epileptic seizures. Interictal epileptiform discharges are activated by sleep deprivation and sleep, and ...some epilepsies occur almost exclusively during sleep. Treatment of sleep-related epilepsy should take in account the type of epileptic syndrome, the type of seizures, the patient characteristics, and also the pharmacokinetics of the drug. Proper characterization of the epilepsy is essential to choose appropriate antiepileptic drugs. Drugs effective in focal epilepsy may be used to treat benign genetic focal epilepsies such as rolandic epilepsy and other focal (frontal or not) sleep epilepsies. These include both classical (such as carbamazepine) and new (such as levetiracetam and lacosamide) antiepileptic drugs. Drug-resistant cases should be evaluated for epilepsy surgery, which may be efficacious in this setting. Valproate, lamotrigine, topiramate, levetiracetam, and perampanel are effective against generalized tonic-clonic seizures in genetic generalized epilepsies, which frequently happen on awakening. Risks of valproate should be considered before prescribing it to women of childbearing age. Specific syndromes such as ESES require specific treatment such as a combination of high dose steroids, benzodiazepines, levetiracetam, and even surgery when an epileptogenic lesion is present. Sleep disorders that may worsen epilepsy such as obstructive sleep apnea or insomnia should be adequately treated to improve seizure frequency. Adequate control of seizures during sleep (especially generalized tonic-clonic seizures) decreases risk of sudden unexpected death in epilepsy (SUDEP).
•Patients with DRE showed greater narcissistic personality disorder symptoms.•Patients with PNES had greater somatization levels.•Seizure frequency was associated with poorer quality of life in ...patients with DRE.•Psychiatric history was associated with poorer quality of life in patients with PNES.•Psychiatric and psychological differences between patients with DRE and PNES were few.
Psychogenic nonepileptic seizures (PNES) are common imitators of epileptic seizures. Refractoriness to antiseizure medication hinders the differential diagnosis between ES and PNES, carrying deleterious consequences in patients with PNES. Psychiatric and psychological characteristics may assist in the differential diagnosis between drug-resistant epilepsy (DRE) and PNES. Nevertheless, current comprehensive psychiatric and psychological descriptive studies on both patient groups are scarce and with several study limitations. This study provides a comprehensive psychiatric and psychological characterization of Spanish patients with DRE and PNES.
A cross-sectional and comparative study was completed with 104 patients with DRE and 21 with PNES. Psychiatric and psychological characteristics were assessed with the HADS, SCL-90-R, NEO-FFI-R, PDQ-4+, COPE, and QOLIE-31 tests. Parametric and non-parametric tests were used, and regression models were fit to further explore factors affecting patients' life quality.
Patients with PNES had greater levels of somatization and extraversion and were associated with benzodiazepine intake. Patients with DRE showed greater narcissistic personality disorder symptoms than those with PNES. In patients with DRE, difficulty in performing basic needs-related tasks and greater psychological distress severity and seizure frequency were associated with poorer life quality. In contrast, being a woman, having a psychiatric disorder history, and greater psychiatric symptoms’ intensity were associated with poorer life quality in patients with PNES.
Patients with DRE and PNES share similar psychiatric and psychological characteristics, with only very few being significantly different.
•New epilepsy definition is considered to treatment decision-making process.•There was not enough evidence on antiseizure monotherapy in all clinical situations.•We present an expert consensus ...guideline recommendation for the treatment of epilepsy.•Type of epilepsy, age, sex, childbearing potential, and comorbidities are considered.
Following publication in 2014 of the International League Against Epilepsy (ILAE) official report changing the definition of epilepsy, a number of questions remain unresolved in regard to deciding when to start treatment and to the choice of a particular antiseizure medication (ASM). This study uses a Delphi method to update consensus among a panel of experts on the initiation of epilepsy treatment in order to provide insight regarding those questions.
The study was undertaken in four phases. Firstly, a multi-center steering committee met to review relevant bibliography and to draft a questionnaire. Secondly, a panel of neurologists specialized in epilepsy was selected and convened. Thirdly, an online survey was carried out in two rounds. Fourthly, the final results were discussed at a face-to-face meeting of the steering committee to draw conclusions. The final questionnaire focused on three independent sections: the decision to commence ASM in different clinical situations, the choice of initial monotherapy depending on the type of epilepsy and the patient’s age/sex (including childbearing potential), and the choice of initial monotherapy depending on comorbidity. In these two latter sections, fourteen ASMs approved for monotherapy use by the EMA and available in Spain were considered.
Regarding the decision as to when to commence treatment, the results show agreement exists to initiate treatment following a first generalized tonic-clonic seizure or a focal seizure if the electroencephalography (EEG) reveals epileptiform activity, if the MRI reveals a lesion, or when it occurs in elderly patients. With respect to the choice of initial monotherapy depending on the type of epilepsy and the patient’s age/sex profile, it is agreed to avoid valproic acid (VPA) in women with childbearing potential, with levetiracetam (LEV) and lamotrigine (LTG) being the preferable options in generalized epilepsy. In focal epilepsy, the options are broader, particularly in men, and include the most recent ASMs approved for monotherapy. In the elderly, LEV, lacosamide (LCM), eslicarbazepine acetate (ESL) and LTG are considered the most suitable drugs for initiating treatment. With regard to comorbidities, the recommendation is to avoid enzyme inducing ASMs, with LEV, the most recent ASMs approved for monotherapy and LTG being the preferred options.
In conclusion, as the ILAE definition states, there are different situations that lead to treatment initiation after a first seizure. When choosing the first ASM, the type of epilepsy, childbearing potential and drug–drug interaction are key factors.
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