Lipodystrophy syndromes are rare diseases of genetic or acquired origin, characterized by quantitative and qualitative defects in adipose tissue. The metabolic consequences of lipodystrophy syndromes, such as insulin resistant diabetes, hypertriglyceridemia and hepatic steatosis, are frequently very difficult to treat, resulting in significant risks of acute and/or chronic complications and of decreased quality of life. The production of leptin by lipodystrophic adipose tissue is decreased, more severely in generalized forms of lipodystrophy, where adipose tissue is absent from almost all body fat depots, than in partial forms of the disease, where lipoatrophy affects only some parts of the body and can be associated with increased body fat in other anatomical regions. Several lines of evidence in preclinical and clinical models have shown that leptin replacement therapy could improve the metabolic complications of lipodystrophy syndromes. Metreleptin, a recombinant leptin analogue, was approved as an orphan drug to treat the metabolic complications of leptin deficiency in patients with generalized lipodystrophy in the USA or with either generalized or partial lipodystrophy in Japan and Europe. In this brief review, we will discuss the benefits and limitations of this therapy, and the new expectations arising from the recent development of a therapeutic monoclonal antibody able to activate the leptin receptor.

The 2017 International League Against Epilepsy (ILAE) classification suggested that the term \"genetic generalized epilepsies\" (GGEs) should be used for the broad group of epilepsies with so-called \"generalized\" seizure types and \"generalized\" spike-wave activity on EEG, based on a presumed genetic etiology. Within this framework, idiopathic generalized epilepsies (IGEs) are described as a subset of GGEs and include only four epileptic syndromes: childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and epilepsy with generalized tonic-clonic seizures alone. The recent 2022 ILAE definition of IGEs is based on the current state of knowledge and reflects a community consensus and is designed to evolve as knowledge advances. The term \"frontiers of IGEs\" refers to the actual limits of our understanding of these four syndromes. Indeed, among patients presenting with a syndrome compatible with the 2022 definition of IGEs, we still observe a significant proportion of patients presenting with specific clinical features, refractory seizures, or drug-resistant epilepsies. This leads to the discussion of the boundaries of IGEs and GGEs, or what is accepted within a clinical spectrum of a definite IGE. Here, we discuss several entities that have been described in the literature for many years and that may either constitute rare features of IGEs or a distinct differential diagnosis. Their recognition by clinicians may allow a more individualized approach and improve the management of patients presenting with such entities.

Cenobamate (CNB), ([(R)-1-(2-chlorophenyl)-2-(2H-tetrazol-2-yl)ethyl], is a novel tetrazole alkyl carbamate derivative. In November 2019, the Food and Drug Administration approved Xcopri®, marketed by SK Life Science Inc., (Paramus, NJ, USA) for adult focal seizures. The European Medicines Agency approved Ontozry® by Arvelle Therapeutics Netherlands B.V.(Amsterdam, The Neatherlands) in March 2021. Cenobamate is a medication that could potentially change the perspectives regarding the management and prognosis of refractory epilepsy. In this way, this study aims to review the literature on CNB\'s pharmacological properties, pharmacokinetics, efficacy, and safety. CNB is a highly effective drug in managing focal onset seizures, with more than twenty percent of individuals with drug-resistant epilepsy achieving seizure freedom. This finding is remarkable in the antiseizure medication literature. The mechanism of action of CNB is still poorly understood, but it is associated with transient and persistent sodium currents and GABAergic neurotransmission. In animal studies, CNB showed sustained efficacy and potency in the 6 Hz test regardless of the stimulus intensity. CNB was revealed to be the most cost-effective drug among different third-generation antiseizure medications. Also, CNB could have neuroprotective effects. However, there are still concerns regarding its potential for abuse and suicidality risk, which future studies should clearly assess, after which protocols should be changed. The major drawback of CNB therapy is the slow and complex titration and maintenance phases preventing the wide use of this new agent in clinical practice.

暂无摘要。

OBJECTIVE: To describe blinking as the only manifestation of seizures from isolated focal and generalized cortical spikes and investigate the relationship between blinks and epileptic discharges.
METHODS: We measured the latency from the onset of spikes to the onset of blinks in two patients using electroencephalogram (EEG) and an electrooculogram (EOG), and calculated the median latency in both cases. We analyzed the latency from spike onset to the onset of additional specific eye movements, seen only in the second case. To determine the frequency of spontaneous blinks (not triggered by spikes), we defined a \"control point\" at 45 s following a random spike for the first case. We tested for statistically significant associations between latencies of blinks (Case 1) as well as between latencies of blinks and specific eye movements (Case 2).
RESULTS: A total of 174 generalized spike-waves followed by a blink were analyzed in the first patient. Approximately 61% of the blinks occurred within 150-450 ms after the onset of the spike. Median latency for blinks following a spike was 294 ms compared to 541 ms for control blinks (p = .02). For the second patient, a total of 160 eye movements following a right occipito-parietal spike were analyzed. The median spike-blink latency in the second case was 497 milliseconds. Median latencies of spike onset to contralateral oblique eye movements with blink and left lateral eye movements were 648 and 655 milliseconds, respectively.
CONCLUSIONS: Our study shows that isolated cortical spikes can induce epileptic seizures consisting exclusively of blinks. These findings emphasize the importance of careful EEG and EOG analysis to determine blinking as the only ictal phenomenon. We additionally describe a new technique to prove the temporal relationship between cortical discharges and a specific movement when, in addition to the movements triggered by a spike, the same movement is also spontaneously performed by the patient (in this case, blinking).

Generalized pustular psoriasis (GPP) is a clinical entity distinct from psoriasis, associated with a poor clinical prognosis, often resulting in severe systemic complications and mortality. The relapsing nature of the disease with recurrent or intermittent flares imposes a significant burden on patients\' quality of life (QoL). Although inadequately studied, QoL data in GPP patients has been a recent point of investigation. We conducted a literature search on PubMed/MEDLINE using the following search terms: \'generalized pustular psoriasis\' OR \'pustular psoriasis\' AND \'quality of life\'. We identified 12 relevant articles that provide insight into the large impact of GPP on the QoL of patients, the burden of the disease and the treatment, and the success of new treatment options in making a clinically important difference to QoL. This review illustrates a need for routine assessment of the QoL in interventional clinical trials for GPP and during physician encounters. This information can help guide clinicians on how to tailor the treatment approach from the patient\'s perspective or illustrate whether new therapies offer meaningful benefits to patient care as we enter an era of exciting new treatments for this challenging condition.

Generalized pustular psoriasis (GPP) is a multisystem disease with potentially life-threatening adverse effects. As patients increasingly seek health information online, and as the landscape for GPP changes, the quality of online health information (OHI) becomes progressively more important. This paper is the first of its kind to examine the quality, comprehensiveness and readability of online health information for GPP. Similar to pre-existing studies evaluating OHI, this paper examines 5 key search terms for GPP- 3 medical and 2 laymen. For each search term, the results were evaluated based on HONcode accreditation, an enhanced DISCERN analysis and a number of readability indices. Of the 500 websites evaluated, 84 (16.8%) were HONcode-accredited. Mean DISCERN scores of all websites were 74.9% and 38.6% for website reliability and treatment sections, respectively, demonstrating key gaps in comprehensiveness and reliability of GPP-specific OHI. Additionally, only 4/100 websites (4%) analysed for readability were written at the NIH-recommended sixth-grade level. Academic websites were significantly more difficult to read than governmental websites. This further exacerbates the patient information gap, particularly for patients with low health literacy, who may already be at higher risk of not receiving timely medical care.

UNASSIGNED: Perampanel is approved for the adjunctive treatment of focal-onset seizures (FOS) with or without secondary generalized seizures. The FAME (Fycompa® as first Add-on to Monotherapy in patients with Epilepsy; NCT02726074) study evaluated the efficacy and safety of perampanel added to monotherapy in patients with FOS with or without secondary generalized seizures (SGS). Post hoc analyses of the FAME study assessed potential predictors of response and an in-depth evaluation of the safety and efficacy of perampanel.
UNASSIGNED: Efficacy was assessed by reduction of total seizure frequency by ≥50%, ≥75% or 100%, and safety by incidence of treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation. Univariate and multivariate logistic regression analyses for treatment response were performed.
UNASSIGNED: Most patients (82/85) received perampanel doses of 4-8 mg/day during maintenance therapy and the highest efficacy rates were achieved with 4 mg/day, irrespective of efficacy outcome. Doses of 4 or 6 mg/day in patients with FOS with SGS (n=16) produced comparable efficacy outcomes. In multivariate analysis, total perampanel dose was predictive of 50% and 75% response rates; longer total perampanel administration period with 50% response; and concomitant non-anti-seizure medication with a 100% response. Patients developed a TEAE more frequently during the 12-week titration period (60.2%) than the 24-week maintenance period (28.4%), including dizziness (45.5% vs. 9.1%), somnolence (10.2% vs. 0%), and headache (4.5% vs. 3.4%).
UNASSIGNED: Post hoc analyses show that even low doses of perampanel may be effective and TEAEs are usually self-limited or well-tolerated.

UNASSIGNED: FAME (Fycompa® as first Add-on to Monotherapy in patients with Epilepsy; NCT02726074), a previously reported single-arm, phase IV study, showed that perampanel improved seizure control as first add-on to failed anti-seizure medication (ASM) monotherapy in 85 South Korean patients aged ≥12 years with focal-onset seizures (FOS) with/without focal to bilateral tonic-clonic seizures. We present results of three post hoc analyses of FAME that further assessed the efficacy and safety of perampanel.
UNASSIGNED: Patients were stratified by low- (4, 6 mg/day) versus high- (8, 10, 12 mg/day) dose maintenance perampanel, perampanel added to first- versus second-line ASM monotherapy, and concomitant background ASM monotherapy and perampanel dose. The primary endpoint was the proportion of patients with a ≥50% reduction in total seizure frequency during the 24-week maintenance period. Safety was assessed by the descriptive incidence of treatment-emergent adverse events (TEAEs).
UNASSIGNED: In post hoc analyses, 50% responder rates were significantly higher for low- versus high-dose maintenance perampanel (88.6% vs. 40.0%; p<0.001) and when added to first- versus second-line ASM monotherapy (83.5% vs. 33.3%; p=0.013). By concomitant background ASM and perampanel maintenance dose, 50% responder rates were 100% for perampanel 4 mg/day added to carbamazepine, oxcarbazepine, lamotrigine, or valproic acid, and 85% when added to levetiracetam. Add-on perampanel improved 75% and seizure-free responder rates, and median percent changes from baseline seizure frequency per 28 days. Perampanel was well tolerated when added to ASM monotherapy, with dizziness being the most common TEAE.
UNASSIGNED: Post hoc analyses of FAME provide supportive data for the use of perampanel as an effective and well-tolerated first add-on treatment to a broad spectrum of ASM monotherapies in patients with FOS.

BACKGROUND: Focal semiologies have been described in idiopathic generalized epilepsies (IGE) and generalized-onset bilateral tonic-clonic seizures (GBTCS). These focal signs may lead to wrong diagnosis and inappropriate choice of antiseizure medications. We sought to investigate the differences in focal semiologic features between GBTCS and focal-onset bilateral tonic-clonic seizures (FBTCS).
METHODS: We retrospectively reviewed video-EEG data of captured GBTCS and FBTCS over a period of five years. The presence or absence of 12 focal signs as well seizure duration and time to head version was tabulated for each seizure. We used the chi-square test for independence and Fisher\'s exact test to investigate the occurrence of each focal sign in FBTCS compared with GBTCS. Additionally, we used receiver operating characteristic (ROC) curves to explore if the seizure duration and time to head version from the ictal onset can reliably differentiate between FBTCS and GBTCS. Finally, we employed hierarchical cluster analysis to visualize how these focal signs appear in combination.
RESULTS: Head version (p <.001), preceding automatisms (p <.001), eye version (p <.001), unilateral facial clonic activity (p <.001), and mouth deviation (p =.004) were found to be significantly more frequent in FBTCS. Longer seizures were highly in favor of FBTCS whereas shorter time to head version from the ictal onset indicated GBTCS in the ROC curve analysis.
CONCLUSIONS: Though focal signs occur in GBTCS, careful evaluation of semiology can help the clinician distinguish FBTCS from GBTCS.