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Comprehensive assessment reveals numerous clinical and neurophysiological differences between MECP2-allelic disorders 综合评估揭示了mecp2等位基因疾病之间的许多临床和神经生理差异。
IF 4.4 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-21 DOI: 10.1002/acn3.52269
Davut Pehlivan, Chengjun Huang, Holly K. Harris, Christine Coquery, Aditya Mahat, Mirjana Maletic-Savatic, Laurence Mignon, Sukru Aras, Daniel G. Glaze, Charles S. Layne, Leonardo Sahelijo, Huda Y. Zoghbi, Matthew J. McGinley, Bernhard Suter

Objective

Rett syndrome (RTT) and MECP2 duplication syndrome (MDS) result from under- and overexpression of MECP2, respectively. Preclinical studies using genetic-based treatment showed robust phenotype recovery for both MDS and RTT. However, there is a risk of converting MDS to RTT, or vice versa, if accurate MeCP2 levels are not achieved. The aim of this study was to identify biomarkers distinguishing RTT from MDS.

Materials and Methods

We prospectively enrolled 11 MDS and 6 male RTT like (MRL) individuals for a panel of clinical and neurophysiological assessments over two visits, 8–10 months apart.

Results

We identified numerous clinical and physiological features as promising biomarkers. MRL individuals exhibited large amplitude whole body tremor, midline stereotypies (vs. hand flapping at sides in MDS), earlier neuromotor regression, and earlier onset but less commonly refractory epilepsy. In the neurophysiological domain, we observed several marked differences in sleep physiology between MDS/MRL and typically developing (TD) individuals including reduced sleeping time, increased delta power during rapid eye movement (REM) sleep, decreased occipital alpha and increased brain-wide delta power during wakefulness, and reduced spindle density and duration. MRL individuals also had much lower delta power during NREM 2 and 3 stages than the TD group. We found differences in spindle duration in the temporal lobes and spindle amplitude in the frontal lobes between MDS and MRL.

Discussion

Our study revealed distinct clinical features of MDS and MRL that can be monitored during a clinical trial and may serve as target engagement, disease progression, or safety biomarkers for interventional studies.

目的:Rett综合征(RTT)和MECP2重复综合征(MDS)分别由MECP2过表达和过表达引起。临床前研究使用基于基因的治疗显示强健的MDS和RTT表型恢复。然而,如果没有达到准确的MeCP2水平,则存在将MDS转化为RTT的风险,反之亦然。本研究的目的是鉴定区分RTT和MDS的生物标志物。材料和方法:我们前瞻性地招募了11名MDS和6名男性RTT样(MRL)个体,在两次访问中进行临床和神经生理评估,间隔8-10个月。结果:我们确定了许多临床和生理特征作为有前途的生物标志物。MRL个体表现为大幅度全身震颤,中线刻板印象(相对于MDS患者的侧手扑动),更早的神经运动消退,更早发病,但罕见的难治性癫痫。在神经生理领域,我们观察到MDS/MRL与正常发育(TD)个体在睡眠时间减少、快速眼动(REM)睡眠时δ波功率增加、清醒时枕α下降和全脑δ波功率增加、纺锤波密度和持续时间减少等睡眠生理学上的几个显著差异。MRL个体在NREM 2和3阶段的δ功率也比TD组低得多。我们发现MDS和MRL在颞叶纺锤波持续时间和额叶纺锤波振幅上存在差异。讨论:我们的研究揭示了MDS和MRL的不同临床特征,这些特征可以在临床试验期间进行监测,并可作为介入研究的靶标参与、疾病进展或安全性生物标志物。
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引用次数: 0
Genotype-function-phenotype correlations for SCN1A variants identified by clinical genetic testing 临床基因检测鉴定的SCN1A变异的基因型-功能-表型相关性
IF 4.4 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-21 DOI: 10.1002/acn3.52297
Andrew T. Knox, Christopher H. Thompson, Dillon Scott, Tatiana V. Abramova, Bethany Stieve, Abigail Freeman, Alfred L. George Jr.

Objective

Interpretation of clinical genetic testing, which identifies a potential genetic etiology in 25% of children with epilepsy, is limited by variants of uncertain significance. Understanding functional consequences of variants can help distinguish pathogenic from benign alleles. We combined automated patch clamp recording with neurophysiological simulations to discern genotype-function-phenotype correlations in a real-world cohort of children with SCN1A-associated epilepsy.

Methods

Clinical data were extracted for children with SCN1A variants identified by clinical genetic testing. Functional properties of non-truncating NaV1.1 variant channels were determined using automated patch clamp recording. Functional data were incorporated into a parvalbumin-positive (PV+) interneuron computer model to predict variant effects on neuron firing and were compared with longitudinal clinical data describing epilepsy types, neurocognitive outcomes, and medication response.

Results

Twelve SCN1A variants were identified (nine non-truncating). Six non-truncating variants exhibited no measurable sodium current in heterologous cells consistent with complete loss of function (LoF). Two variants caused either partial LoF (L479P) or a mixture of gain and loss of function (I1356M). The remaining non-truncating variant (T1250M) exhibited normal function. Functional data changed classification of pathogenicity for six variants. Complete LoF variants were universally associated with seizure onset before one year of age and febrile seizures, and were often associated with drug resistant epilepsy and below average cognitive outcomes. Simulations demonstrated abnormal firing in heterozygous model neurons containing dysfunctional variants.

Interpretation

In SCN1A-associated epilepsy, functional analysis and neuron simulation studies resolved variants of uncertain significance and correlated with aspects of phenotype and medication response.

目的:临床基因检测在25%的癫痫患儿中发现了潜在的遗传病因,但其解释受到不确定意义变异的限制。了解变异的功能后果可以帮助区分致病等位基因和良性等位基因。我们将自动膜片钳记录与神经生理学模拟相结合,在现实世界的scn1a相关癫痫患儿队列中识别基因型-功能-表型相关性。方法:提取经临床基因检测发现的SCN1A变异体患儿的临床资料。使用自动膜片钳记录确定非截断的NaV1.1变异通道的功能特性。将功能数据纳入小蛋白阳性(PV+)中间神经元计算机模型,以预测神经元放电的变异影响,并将其与描述癫痫类型、神经认知结果和药物反应的纵向临床数据进行比较。结果:鉴定出12个SCN1A变异(9个非截断)。6个非截断变异在异源细胞中没有可测量的钠电流,这与功能完全丧失(LoF)一致。两个变体导致部分失活(L479P)或功能增益和功能丧失的混合(I1356M)。其余未截断的变体(T1250M)功能正常。功能数据改变了6个变异的致病性分类。完全LoF变异普遍与一岁前癫痫发作和热性癫痫发作相关,并且通常与耐药癫痫和低于平均水平的认知结果相关。模拟表明,杂合模型神经元中含有功能失调的变体,其放电异常。解释:在scn1a相关癫痫中,功能分析和神经元模拟研究解决了不确定意义的变异,并与表型和药物反应相关。
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引用次数: 0
Blended phenotype of TECPR2-associated hereditary sensory-autonomic neuropathy and Temple syndrome 与tecpr2相关的遗传性感觉-自主神经病变和Temple综合征的混合表型。
IF 4.4 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-14 DOI: 10.1002/acn3.52293
Umar Zubair, Kathryn Yang, Luca Schierbaum, Amy Tam, Nicole Battaglia, Joshua Rong, Vicente Quiroz, Darius Ebrahimi-Fakhari

Uniparental isodisomy (UPiD) can cause mixed phenotypes of imprinting disorders and autosomal-recessive diseases. We present the case of a 3-year-old male with a blended phenotype of TECPR2-related hereditary sensory and autonomic neuropathy (HSAN9) and Temple syndrome (TS14) due to maternal UPiD of chromosome 14, which includes a loss-of-function founder variant in the TECPR2 gene [NM_014844.5: c.1319del, p.Leu440Argfs*19]. This case illustrates challenges associated with a mixed phenotype of ultra-rare disorders and underscores the importance of investigating recessive conditions in homozygosity regions when atypical clinical features occur in patients with well-characterized imprinting disorders.

单亲同染色体(UPiD)可引起印迹疾病和常染色体隐性疾病的混合表型。我们报告了一例3岁男性,由于母亲14号染色体的UPiD,其混合表型为TECPR2相关的遗传性感觉和自主神经病变(HSAN9)和Temple综合征(TS14),其中包括TECPR2基因的功能缺失的创始人变异[NM_014844.5: c.1319del, p.Leu440Argfs*19]。该病例说明了与超罕见疾病的混合表型相关的挑战,并强调了当非典型临床特征出现在具有良好特征的印迹疾病患者中时,研究纯合区域隐性条件的重要性。
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引用次数: 0
Demyelinating neuropathy as the initial presentation of familial E200K Creutzfeldt–Jakob disease in two patients 脱髓鞘神经病变作为家族性E200K克雅氏病两例患者的初始表现
IF 4.4 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-12 DOI: 10.1002/acn3.52296
Cécile Delorme, Antoine Pégat, Julian Theuriet, Jean-Philippe Brandel, Emmanuel Roze, Karine Viala, Julie Zyss, Stéphane Thobois, Anthony Fourier, Emilien Bernard, Juliette Svahn, Chloé Laurencin, Paul Jaulent, Christophe Vandendries, Isabelle Quadrio, Virginie Desestret, David Meyronet, Thierry Maisonobe, Stéphane Haïk, Danielle Seilhean

Objective

To describe peripheral neuropathy associated with familial Creutzfeldt-Jakob disease.

Methods

We report two unrelated patients with genetic Creutzfeldt–Jakob disease with demyelinating peripheral neuropathy as initial presentation, with a comprehensive clinical, electrophysiological and neuropathological description.

Results

Both patients exhibited gait disturbance and paresthesia. Electrodiagnostic studies revealed demyelinating abnormalities with motor conduction blocks suggestive of chronic inflammatory demyelinating polyradiculoneuropathy, with abnormal plexus MRI and elevated CSF protein levels. One of them had pes cavus and a late-onset Charcot–Marie-Tooth (CMT) disease was also initially hypothesized. Central nervous system involvement manifested 1–2 years after the onset of peripheral symptoms. Both patients had a heterozygous E200K mutation in the PRNP gene. Postmortem neuropathological examinations showed PrPSc deposits in the peripheral nervous system, particularly in Schwann cells. Interpretation: Peripheral neuropathy in E200K genetic forms of Creutzfeldt-Jakob disease can be inaugural and mimic chronic inflammatory demyelinating polyradiculoneuropathy.

目的:探讨与家族性克雅氏病相关的周围神经病变。方法:我们报告了两例不相关的遗传性克雅氏病合并脱髓鞘周围神经病变的首发表现,并进行了全面的临床、电生理和神经病理描述。结果:两例患者均表现出步态障碍和感觉异常。电诊断显示脱髓鞘异常,运动传导阻滞提示慢性炎性脱髓鞘性多根神经病变,神经丛MRI异常,脑脊液蛋白水平升高。其中一人患有足弓足,并最初假设为迟发性腓骨肌痛(CMT)病。外周症状出现后1-2年中枢神经系统受累。两例患者均存在PRNP基因的杂合E200K突变。死后神经病理学检查显示PrPSc沉积于周围神经系统,尤其是雪旺细胞。解释:E200K遗传型克雅氏病的周围神经病变可能是初始的,类似慢性炎症性脱髓鞘性多神经根神经病变。
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引用次数: 0
Interaction between riluzole treatment and dietary glycemic index in the disease progression of amyotrophic lateral sclerosis 利鲁唑治疗与饮食血糖指数在肌萎缩侧索硬化疾病进展中的相互作用。
IF 4.4 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-09 DOI: 10.1002/acn3.52294
Ikjae Lee, Hiroshi Mitsumoto, Seonjoo Lee, Edward Kasarskis, Michael Rosenbaum, Pam Factor-Litvak, Jeri W. Nieves

Objective

We examined whether riluzole treatment modifies the associations between the dietary glycemic index (GI) and load (GL) and disease progression in amyotrophic lateral sclerosis (ALS).

Methods

Sporadic ALS patients in the Multicenter Cohort Study of Oxidative Stress who completed a baseline food frequency questionnaire were included (n = 304). Interactions between baseline riluzole treatment and GI/GL on functional decline and tracheostomy-free survival were examined using linear regression and Cox proportional hazard models adjusted for covariates. Age, sex, disease duration, diagnostic certainty, body mass index, bulbar onset, revised ALS functional rating scale (ALSFRS-r) total score, and forced vital capacity, from baseline were included as covariates.

Results

Baseline higher GI and GL were associated with less decline of ALSFRS-r total score at 3-month follow-up in the riluzole treatment group (RTG) but not in the no-riluzole group (NRG). When quartile groups were used, GI second [β = −1.9, 95% CI (−4.1, −0.2), p = 0.07], third [β = −3.0, 95% CI (−5.1, −0.8), p < 0.01] and fourth [β = −2.2, 95% CI (−4.3, −0.01), p < 0.05] quartile groups were associated with less ALSFRS-r decline at 3-months compared to the first quartile group (GI < 47.2) among the RTG. Similarly, GL fourth quartile group (GL > 109.5) was associated with less ALSFRS-r decline at 3 months compared to the first quartile group [β = −2.6, 95% CI (−4.7, −0.5), p < 0.05] among the RTG. In NRG, no statistically significant differences in ALSFRS-r decline were found among GI/GL quartile groups.

Interpretation

High dietary GI and GL are associated with a slower functional decline only among ALS patients taking riluzole.

目的:研究利鲁唑治疗是否能改变肌萎缩性侧索硬化症(ALS)患者饮食血糖指数(GI)和负荷(GL)与疾病进展之间的关系。方法:纳入多中心队列氧化应激研究中完成基线食物频率问卷调查的散发性ALS患者(n = 304)。采用线性回归和Cox比例风险模型对协变量进行校正,检验利鲁唑基线治疗与GI/GL对功能下降和气管造口无生存的相互作用。从基线开始,年龄、性别、病程、诊断确定性、体重指数、球发病、修订的ALS功能评定量表(ALSFRS-r)总分和用力肺活量被纳入协变量。结果:利鲁唑治疗组(RTG) 3个月随访时基线较高的GI和GL与ALSFRS-r总分下降较少相关,而非利鲁唑组(NRG)则不然。当使用四分位数组时,与第一个四分位数组相比,GI第二组[β = -1.9, 95% CI (-4.1, -0.2), p = 0.07], GI第三组[β = -3.0, 95% CI (-5.1, -0.8), p 109.5]与3个月时ALSFRS-r下降较少相关[β = -2.6, 95% CI (-4.7, -0.5), p]解释:高饮食GI和GL仅与服用利鲁唑的ALS患者较慢的功能下降有关。
{"title":"Interaction between riluzole treatment and dietary glycemic index in the disease progression of amyotrophic lateral sclerosis","authors":"Ikjae Lee,&nbsp;Hiroshi Mitsumoto,&nbsp;Seonjoo Lee,&nbsp;Edward Kasarskis,&nbsp;Michael Rosenbaum,&nbsp;Pam Factor-Litvak,&nbsp;Jeri W. Nieves","doi":"10.1002/acn3.52294","DOIUrl":"10.1002/acn3.52294","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We examined whether riluzole treatment modifies the associations between the dietary glycemic index (GI) and load (GL) and disease progression in amyotrophic lateral sclerosis (ALS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Sporadic ALS patients in the Multicenter Cohort Study of Oxidative Stress who completed a baseline food frequency questionnaire were included (<i>n</i> = 304). Interactions between baseline riluzole treatment and GI/GL on functional decline and tracheostomy-free survival were examined using linear regression and Cox proportional hazard models adjusted for covariates. Age, sex, disease duration, diagnostic certainty, body mass index, bulbar onset, revised ALS functional rating scale (ALSFRS-r) total score, and forced vital capacity, from baseline were included as covariates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Baseline higher GI and GL were associated with less decline of ALSFRS-r total score at 3-month follow-up in the riluzole treatment group (RTG) but not in the no-riluzole group (NRG). When quartile groups were used, GI second [β = −1.9, 95% CI (−4.1, −0.2), <i>p</i> = 0.07], third [β = −3.0, 95% CI (−5.1, −0.8), <i>p</i> &lt; 0.01] and fourth [β = −2.2, 95% CI (−4.3, −0.01), <i>p</i> &lt; 0.05] quartile groups were associated with less ALSFRS-r decline at 3-months compared to the first quartile group (GI &lt; 47.2) among the RTG. Similarly, GL fourth quartile group (GL &gt; 109.5) was associated with less ALSFRS-r decline at 3 months compared to the first quartile group [β = −2.6, 95% CI (−4.7, −0.5), <i>p</i> &lt; 0.05] among the RTG. In NRG, no statistically significant differences in ALSFRS-r decline were found among GI/GL quartile groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>High dietary GI and GL are associated with a slower functional decline only among ALS patients taking riluzole.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 3","pages":"491-498"},"PeriodicalIF":4.4,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52294","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tofersen treatment leads to sustained stabilization of disease in SOD1 ALS in a “real-world” setting 在“现实世界”环境中,托佛森治疗可使SOD1型ALS患者的病情持续稳定。
IF 4.4 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-09 DOI: 10.1002/acn3.52264
Sean E. Smith, Kelly McCoy-Gross, Amber Malcolm, Jeri Oranski, Jesse W. Markway, Timothy M. Miller, Robert C. Bucelli

Objective

Patients with amyotrophic lateral sclerosis (ALS) caused by superoxide dismutase 1 (SOD1) gene mutations (SOD1 ALS) treated with tofersen have shown slowing of disease progression, and disease stabilization with recovery of function in some patients. We report our clinical experience with treating patients with SOD1 ALS and the effects of tofersen on outcome measures.

Methods

This was a single-center observational study of patients with SOD1 ALS receiving treatment with tofersen. The effects of tofersen treatment on neurofilament levels, muscle strength, and clinical outcome measures were assessed. Several patients had outpatient neuromuscular rehabilitation in addition to tofersen treatment and we report changes in functional outcomes.

Results

Seven SOD1 ALS patients received treatment at our institution. All patients showed robust and sustained declines in serum NfL and CSF pNFH (mean change serum NfL: −57.9%; mean change CSF pNFH: −67.6%). There was apparent disease stabilization as assessed by the ALSFRS-R total score, mean change 1.1 (SD = 0.7). There was notable improvement in functional independence measured by the FIM motor score, mean change 5.13 points (SD = 3.85).

Interpretation

This study provides evidence that tofersen treatment in SOD1 ALS can lead to meaningful preservation of function and suggestions of sustained improvement in neurologic function in some patients, and strongly supports the role of neurofilaments as therapeutic biomarkers.

目的:豆腐素治疗由超氧化物歧化酶1 (SOD1)基因突变(SOD1 ALS)引起的肌萎缩性侧索硬化症(ALS)患者,可减缓疾病进展,部分患者病情稳定,功能恢复。我们报告了治疗SOD1 ALS患者的临床经验和托福素对结果测量的影响。方法:这是一项单中心观察性研究,研究对象是接受豆腐素治疗的SOD1 ALS患者。评估豆腐素治疗对神经丝水平、肌肉力量和临床结果的影响。一些患者除了接受托佛森治疗外,还接受了门诊神经肌肉康复治疗,我们报告了功能结果的变化。结果:7例SOD1 ALS患者在我院接受治疗。所有患者血清NfL和脑脊液pNFH均出现强劲且持续的下降(血清NfL平均变化:-57.9%;CSF pNFH平均变化:-67.6%)。通过ALSFRS-R总分评估,疾病明显稳定,平均变化1.1 (SD = 0.7)。FIM运动评分测量的功能独立性显著改善,平均变化5.13分(SD = 3.85)。解释:本研究提供的证据表明,豆腐素治疗SOD1 ALS可以导致有意义的功能保存,并提示一些患者神经功能持续改善,并强烈支持神经丝作为治疗性生物标志物的作用。
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引用次数: 0
Correction to “Infantile Krabbe disease (0–12 months), progression, and recommended endpoints for clinical trials” 修正为“婴儿克拉伯病(0-12个月)、进展和推荐的临床试验终点”。
IF 4.4 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-09 DOI: 10.1002/acn3.52275

Article AID: ACN352114

Table 1

On Page 4, age at first evaluation for HSCT asymptomatic group should have a maximum of 40.7 not 40.1.

For initial psychosine levels, please update natural history median to 22.3 and range to 0.99–82.3, symptomatic HSCT median to 28.1 and range to 4.09–54.0, and asymptomatic HSCT range to 1.03–29.1.

For initial GALC levels, please update symptomatic HSCT median to 0.01 and asymptomatic HSCT range to 0.02–0.23.

Table 2

On Page 5, please update heading to say, “Summary of the growth percentiles in Natural History, Symptomatic HSCT, and Asymptomatic HSCT patients, indicating percentages below the third percentile for head circumference and below the fifth percentile for height, weight, and body mass index.”

Sitting

On Page 8, please update the last sentence from “52%” to “53%,” and replace “Table S6” with “Table S7” in the last sentence.

Neurodevelopmental Function

On Pages 10–11, the last sentence in the first paragraph of Page 11 (“The Asympt HSCT group showed higher scores and greater gains over time than both the NH and Sympt HSCT groups for all domains (all p < 0.001) (Table S9).”) needs to be moved to Page 10 just after “(Figs. S2 and S3, Table S8).” and before “The group performed slightly better….”

Supporting Information

Table S4

Table S4 is incorrectly listed as Table S5.

Tables S7, S8, and S9

Table S7 is incorrectly listed as Table S9. Table S8 is incorrectly listed as Table S7. Table S9 is incorrectly listed as Table S8.

Additionally, the tables and figures under Supporting Information do not have numbers or legends when downloaded. To address all issues, we have prepared new, reformatted PDFs with correct figure numbers and legends to be included in Supporting Information. Please just replace those files with the new ones provided. Thank you!

We apologize for these errors.

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引用次数: 0
Psychiatric manifestations of encephalitis 脑炎的精神表现。
IF 4.4 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-07 DOI: 10.1002/acn3.52260
Paris Bean, Ashley Heck, Ralph Habis, Swathi Sowmitran, Zoe Cartaina, Rajesh Gupta, John Probasco, Rodrigo Hasbun, Arun Venkatesan

Objective

Encephalitis is a serious and potentially life-threatening condition of infectious or autoimmune cause. We aim to characterize the frequency and clinical spectrum of presenting psychiatric symptoms in encephalitis in order to inform earlier recognition and initiation of treatment.

Methods

This was a retrospective study of adult patients who met the 2013 International Encephalitis Consortium (IEC) and/or 2016 Graus criteria between February 2005 and February 2023. The study included two hospital systems in Houston, Texas, and Baltimore, Maryland and included a total of 642 patients. Psychiatric manifestations were grouped into five high-level categories: behavior, psychosis, mood, sleep disturbances, and catatonia.

Results

In our cohort of 642 patients, 318 (49.6%) had psychiatric symptoms at the time of initial presentation, including 78.2% with autoimmune etiologies and 35.2% with viral etiologies (P < 0.001). Those with psychiatric symptoms were younger (median age 47.5 vs. 51.5; P < 0.001), and more likely to have a history of documented psychiatric disorders, as well as longer lengths of hospital stay, and poorer discharge outcomes. Of patients initially admitted to a psychiatric service (n = 28), most had autoimmune causes, although 3 out of 28 (10.7%) had herpes viral infections; admission to a psychiatric service was associated with substantially longer interval to initiation of antivirals and immunotherapy. Autoimmune and infectious etiologies differed in the spectrum and frequency of psychiatric manifestations.

Interpretation

Psychiatric symptoms are common across etiologies of encephalitis and are associated with longer lengths of hospital stay and worse clinical outcomes. Specific patterns and dimensionality of psychiatric symptoms distinguish autoimmune from infectious causes.

目的:脑炎是一种严重且可能危及生命的感染性或自身免疫性疾病。我们的目的是表征脑炎中出现精神症状的频率和临床谱,以便告知早期识别和开始治疗。方法:对2005年2月至2023年2月期间符合2013年国际脑炎联合会(IEC)和/或2016年Graus标准的成年患者进行回顾性研究。该研究包括德克萨斯州休斯顿和马里兰州巴尔的摩的两个医院系统,共包括642名患者。精神病学表现分为五个高级类别:行为、精神病、情绪、睡眠障碍和紧张症。结果:在我们的642例患者队列中,318例(49.6%)在首次就诊时出现精神症状,其中78.2%为自身免疫性病因,35.2%为病毒病因(P解释:精神症状在脑炎病因中很常见,并与较长的住院时间和较差的临床结果相关。精神症状的特定模式和维度将自身免疫与感染性病因区分开来。
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引用次数: 0
Reactivation and consolidation of memory traces during post-encoding rest across the adult lifespan 编码后休息期间记忆痕迹的再激活和巩固。
IF 4.4 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-07 DOI: 10.1002/acn3.52290
Destaw B. Mekbib, Ian M. McDonough

Episodic memory is a critical cognitive function that enables the encoding, storage, and retrieval of new information. Memory consolidation, a key stage of episodic memory, stabilizes this newly encoded information into long-lasting brain “storage.” Studies using fMRI to investigate post-encoding awake rest holds promise to shed light on early, immediate consolidation mechanisms. Here, we review fMRI studies during episodic memory to document common methods to investigate post-encoding consolidation, such as multivoxel pattern analysis (MVPA) and functional connectivity, and the current state of the science in both healthy younger and older adults. In young adults, post-encoding reactivation of stimuli-specific neural patterns in the hippocampus and its connectivity with cortical and subcortical areas (e.g., visual-temporal cortex, medial prefrontal, and medial parietal cortex) correlate with subsequent memory performance. Conversely, studies in older adults highlight the importance of large-scale brain networks during post-encoding rest, particularly the default mode network (DMN). Alterations in connectivity between the DMN and task-positive networks may help older adults maintain episodic memory. Furthermore, non-invasive brain stimulation techniques can enhance these post-encoding consolidation processes and improve memory performance in both younger and older adults. Notably, a lack of studies has investigated post-encoding memory consolidation in neurodegenerative disorders. This review underscores the importance of understanding how post-encoding neural reactivation and connectivity evolve with age to partially explain age-related declines in episodic memory performance and how such declines can be restored.

情景记忆是一种重要的认知功能,它使新信息的编码、存储和检索成为可能。记忆巩固是情景记忆的关键阶段,它将这些新编码的信息稳定在大脑的长期“存储”中。利用功能磁共振成像(fMRI)研究编码后的清醒休息,有望揭示早期、即时的巩固机制。在这里,我们回顾了情景记忆期间的fMRI研究,以记录研究编码后巩固的常用方法,如多体素模式分析(MVPA)和功能连接,以及健康年轻人和老年人的科学现状。在年轻人中,海马中刺激特异性神经模式的编码后再激活及其与皮层和皮层下区域(例如,视觉颞叶皮层、内侧前额叶皮层和内侧顶叶皮层)的连通性与随后的记忆表现相关。相反,对老年人的研究强调了编码后休息期间大规模大脑网络的重要性,特别是默认模式网络(DMN)。DMN和任务积极网络之间连接的改变可能有助于老年人维持情景记忆。此外,非侵入性脑刺激技术可以增强这些编码后巩固过程,并改善年轻人和老年人的记忆表现。值得注意的是,缺乏关于编码后记忆巩固在神经退行性疾病中的研究。这篇综述强调了理解编码后神经再激活和连接如何随着年龄的增长而进化的重要性,以部分解释与年龄相关的情景记忆表现下降以及如何恢复这种下降。
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引用次数: 0
Case of a 57-year-old woman with acute confusion and inability to recognize her husband 一名57岁妇女急性神志不清,认不出自己的丈夫。
IF 4.4 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-07 DOI: 10.1002/acn3.52289
Elizabeth Anderson

Patient is a 57-year-old Hispanic female with a past medical history of hypertension, asthma, and type II diabetes mellitus who presented to the emergency room (ER) for evaluation of 7 days of altered mental status. Upon initial presentation, the patient had difficulty following one step commands and was not fully oriented. Additionally, she appeared to be responding to external auditory and visual stimuli. Magnetic resonance imaging (MRI) completed in the ER was without acute intracranial abnormality (Figure 1), and electroencephalogram (EEG) was significant for diffuse slowing but no epileptiform activity was noted. She was admitted to the neurology service for further workup and treatment for possible autoimmune encephalitis, plasma exchange (PLEX), high-dose steroids, as well as intravenous immunoglobulin (IVIG) treatments. However, despite treatments, the patient continued to remain altered. Therefore, psychiatry was consulted as well as a cognitive specialist. Per patient's husband, he was able to recall that she had in fact had several years of cognitive decline, periods of altered mental status, hallucinations, and slowed gait. During her admission she had periods of not recognizing her husband, and identified him as an imposter, consistent with Capgras syndrome.1 Given clinical findings, our cognitive team determined the patient's most likely diagnosis and started her on rivastigmine 1.5 mg bid with improvement.2

Lewy body dementia.

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引用次数: 0
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Annals of Clinical and Translational Neurology
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