Neurology. Clinical practice最新文献

{"title":"Clinically Suspected Neurodegeneration in Histiocytic Neoplasms as Causes of Neurologic Decline: A Retrospective Study.","authors":"Amir Barmada, Ronald S Go, John C Benson, Gaurav Goyal, W Oliver Tobin","doi":"10.1212/CPJ.0000000000200579","DOIUrl":"10.1212/CPJ.0000000000200579","url":null,"abstract":"<p><strong>Objectives: </strong>The aim of this study was to evaluate the causes of suspected neurodegeneration in adults with histiocytic neoplasms.</p><p><strong>Methods: </strong>Patients with histiocytic neoplasms were identified. Inclusion criteria were (1) diagnosis of histiocytic neoplasm; (2) the treating hematologist suspected neurodegeneration; and (3) patients age 18 years or older. Active CNS histiocytic neoplasm was defined as new or enlarging T2 lesions, or gadolinium enhancing lesions on MRI.</p><p><strong>Results: </strong>Neurodegeneration was suspected in 23 of 478 patients. A progressive neurologic disorder was confirmed in 15 of 23 patients and was associated with an underlying active (12/15) or inactive (3/15) histiocytic neoplasm. Of the 8 patients without a progressive neurologic disorder, diagnoses included fixed deficit from histiocytic neoplasm (3/8), depression (2/8), fatigue (1/8), pain (1/8), and stroke (1/8). Of the 3 of 15 patients with progressive neurologic dysfunction and inactive CNS histiocytic neoplasm, all had progressive pontocerebellar dysfunction. Progressive pontocerebellar atrophy on MRI was present in 10 of 13 patients with progressive symptoms, and 2 of 6 patients with no progressive symptoms.</p><p><strong>Discussion: </strong>Progressive neurologic dysfunction in adult patients with histiocytic neoplasms is most frequently because of an active histiocytic neoplasm or nonhistiocytic etiology. A minority of patients have presumed nonneoplastic progressive neurologic dysfunction, primarily associated with pontocerebellar atrophy.</p>","PeriodicalId":19136,"journal":{"name":"Neurology. Clinical practice","volume":"16 2","pages":"e200579"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12802971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145990209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The SIH Impact Inventory: A Pilot Study of a Novel Instrument Assessing Quality of Life in Spontaneous Intracranial Hypotension.","authors":"Victor Liaw, Deborah I Friedman","doi":"10.1212/CPJ.0000000000200585","DOIUrl":"10.1212/CPJ.0000000000200585","url":null,"abstract":"<p><strong>Background and objectives: </strong>Spontaneous intracranial hypotension (SIH) profoundly affects quality of life. We aimed to identify and quantify various aspects of patients' experiences with SIH.</p><p><strong>Methods: </strong>We piloted an \"SIH Impact Inventory,\" a cross-sectional survey developed in collaboration with patients, family members, and caregivers. Potential participants were identified from a single center using diagnosis and procedure codes. Participants completed the inventory online using REDCap between December 2021 and April 2022.</p><p><strong>Results: </strong>Ninety-eight adult patients completed the inventory. The mean age was 50.6 years, and 69.4% were female. Sixty-three percent had a confirmed diagnosis of SIH, and 36.7% had clinically suspected but unconfirmed SIH. The mean time to diagnosis was 2.0 (interquartile range: 0.5-4.8) years; 25.5% went undiagnosed for 5 or more years, and 75% were initially misdiagnosed. The 3 most common symptoms were head pain, neck pain, and \"brain fog.\" Of those undergoing epidural blood patch procedures, 22% experienced relief of symptoms for a median time of 1.3 months; those with a confirmed diagnosis had more prolonged relief. 58.2% reported experiencing rebound intracranial hypertension after a therapeutic procedure. Surgical repair of the leak was most likely to result in a symptom-free status (<i>p</i> = 0.003) than nonsurgical treatments. Of those working for compensation when they developed SIH, 95.2% indicated that the condition affected their ability to work and 65.1% stopped working. The financial burden was substantial for 65.3% of our cohort, with medical expenses (98.4%) and travel for health care (65.6%) being the most prevalent expenses. SIH negatively affected personal and family relationships for most patients.</p><p><strong>Discussion: </strong>Individuals with confirmed and suspected SIH experience difficulties related to the disorder itself and the lengthy process of diagnosis and treatment. Our findings demonstrate the marked impact of SIH on employment, education, interpersonal relationships, and finances. Compared with previous studies, our cohort reported considerable cognitive difficulties, with rates approaching those of head pain. Heightened awareness of SIH, referral to a center with expertise in SIH, increasing the number and geographic distribution of SIH centers, and advances in diagnostic and treatment modalities can help alleviate some of the challenges that patients face.</p>","PeriodicalId":19136,"journal":{"name":"Neurology. Clinical practice","volume":"16 2","pages":"e200585"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12854680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146106470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of IV Ketamine in Refractory/Super-Refractory Status Epilepticus: A Systematic Review and Meta-Analysis.","authors":"Abhijit Vijay Lele, Alex Raquer, Jorge Mejia-Mantilla, Samuel Ern Hung Tsan, Gentle Sunder Shrestha, Victor Lin, Samuel Neal Blacker, Sean Marinelli, Peter Chee Seong Tan, Sarah Wahlster, Andres Gempeler","doi":"10.1212/CPJ.0000000000200584","DOIUrl":"10.1212/CPJ.0000000000200584","url":null,"abstract":"<p><strong>Background and objectives: </strong>Intravenous ketamine is increasingly used for refractory and super-refractory status epilepticus (RSE/SRSE), yet its efficacy and optimal use remain uncertain. We therefore aimed to synthesize the available evidence to quantify the effectiveness of ketamine in achieving seizure cessation and to explore differences in treatment characteristics between patients who respond and those who do not.</p><p><strong>Methods: </strong>We conducted a systematic review and meta-analysis to estimate the pooled seizure cessation rate associated with intravenous ketamine. Secondary analyses compared ketamine initiation timing, dosing, and infusion duration between patients who achieved seizure cessation (responders) and those who did not (nonresponders).</p><p><strong>Results: </strong>Fourteen studies comprising 388 adult patients (249 responders, 139 nonresponders) were included. The pooled seizure cessation rate with ketamine was 64% (95% CI 49%-76%) with moderate heterogeneity (<i>I</i> ² = 54.1%). Sensitivity analysis showed no single study substantially influenced results, supporting robustness. Responders received ketamine earlier (3.2 ± 2.6 days) than non-responders (4.3 ± 2.6 days), mean difference of -0.90 days (95% CI: -1.31 to -0.49; <i>p</i> < 0.0001). The mean maintenance dose was 2.5 ± 1.4 mg/kg/hr (responders: 2.5 ± 1.3; nonresponders: 2.6 ± 1.4), with no significant difference between groups (mean difference -0.14 mg/kg/hr; 95% CI -0.45 to 0.18; <i>p</i> = 0.39). Infusion duration averaged 5.0 ± 4.2 days in both groups, with no significant difference (mean difference -0.07 days; 95% CI -1.02 to 0.88; <i>p</i> = 0.88). Ketamine discontinuation due to adverse events was rare (0.7%, 3/55 patients).</p><p><strong>Discussion: </strong>Intravenous ketamine demonstrates consistent effectiveness and safety as an adjunctive therapy in RSE/SRSE. However, the timing of initiation cannot be reliably linked to improved clinical outcomes given current methodological limitations and heterogeneity across studies. Future prospective research using standardized definitions and rigorous temporal data collection is needed to clarify whether the timing of ketamine initiation independently influences therapeutic success and to define its optimal integration within established status epilepticus (SE) treatment algorithms.</p><p><strong>Registration: </strong>The systematic review was registered (June 7, 2024) with the International Prospective Register of Systematic Reviews (PROSPERO, CRD42024549523).</p>","PeriodicalId":19136,"journal":{"name":"Neurology. Clinical practice","volume":"16 2","pages":"e200584"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12807489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Neurology Models for Population Health: Case Studies and Lessons From Academic Health Systems.","authors":"Lidia M V R Moura, Meghan Kotarski, Lyell K Jones, Merit Cudkowicz","doi":"10.1212/CPJ.0000000000200582","DOIUrl":"10.1212/CPJ.0000000000200582","url":null,"abstract":"<p><strong>Background: </strong>Neurologic disorders are a leading cause of disability worldwide, yet US specialty care remains fragmented and reactive. Integrated population-health models that embed neurology within coordinated systems can improve access, efficiency, and outcomes.</p><p><strong>Recent findings: </strong>We reviewed case studies from 5 diverse academic health systems-Cleveland Clinic, Mayo Clinic, Mass General Brigham, Kaiser Permanente, and Vanderbilt University Medical Center. Strategies included embedding neurologists in primary care, deploying low-cost telehealth networks, and aligning incentives for value-based care. These programs demonstrated improved timeliness, patient satisfaction, and resource utilization, while highlighting persistent challenges such as reimbursement uncertainty, workforce burnout, and digital inequities.</p><p><strong>Implications for practice: </strong>Key elements-team-based care, telehealth, and shared governance-are adaptable beyond large academic centers. Transparent cost analyses, alternative payment models, and policies addressing licensure and equity will be essential to scale integrated neurology and sustain innovation across community and rural settings.</p>","PeriodicalId":19136,"journal":{"name":"Neurology. Clinical practice","volume":"16 2","pages":"e200582"},"PeriodicalIF":3.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13245196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dopaminergic Pathway Imaging: A Visual and Educational Guide.","authors":"Michal Pudis, Laura Rodríguez-Bel, Montserrat Cortés-Romera, Marina Suárez-Piñera","doi":"10.1212/CPJ.0000000000200599","DOIUrl":"10.1212/CPJ.0000000000200599","url":null,"abstract":"<p><strong>Purpose of review: </strong>Dopaminergic molecular imaging has evolved from an esoteric research tool to an indispensable adjunct in the diagnosis, management, and teaching of movement and neuropsychiatric disorders. Despite its clinical relevance, many neurology trainees encounter dopamine transporter (DAT) SPECT, [18F]FDOPA PET, and emerging vesicular monoamine transporter-2 (VMAT2) tracers only sporadically and often without a cohesive interpretive framework. This narrative review aims to provide a visually driven, clinically grounded roadmap that links dopaminergic neurochemistry and pathway anatomy to in vivo molecular imaging, with a specific focus on education and bedside application.</p><p><strong>Recent findings: </strong>Advances in dopaminergic imaging now allow in vivo interrogation of dopamine synthesis, vesicular storage, synaptic reuptake, postsynaptic receptor signaling, and metabolism using complementary SPECT and PET radiotracers. Presynaptic techniques (FDOPA PET, VMAT2 PET, or DAT SPECT/PET) reliably detect nigrostriatal degeneration, clarify equivocal parkinsonian presentations, and highlight phenotypic variants, including genetic and drug-related mimics. Postsynaptic D₂/D₃ receptor imaging refines differentiation between neurodegenerative and drug-induced parkinsonism, whereas myocardial [123I]-MIBG scintigraphy adds autonomic context that strengthens separation of synucleinopathies from tauopathies. Educational strategies increasingly emphasize pathway-based interpretation, recognition of common pitfalls (such as false-negative DAT scans), and the integration of semiquantitative metrics. Emerging machine learning approaches and standardized quantification pipelines are improving reproducibility and scalability across centers.</p><p><strong>Summary: </strong>By integrating dopaminergic pathway anatomy, molecular neurotransmission, and tracer-specific imaging patterns, dopaminergic scans can be transformed from isolated diagnostic tests into powerful clinical and educational tools. A visually anchored, circuit-based teaching approach-supported by schematic figures, comparative tables, and case-based discussion-enhances trainee understanding and clinical confidence. This guide aims to equip neurologists and trainees with a coherent framework for deploying dopaminergic imaging effectively at the bedside and in the classroom, while preparing the field for quantitative and theragnostic advances.</p>","PeriodicalId":19136,"journal":{"name":"Neurology. Clinical practice","volume":"16 2","pages":"e200599"},"PeriodicalIF":3.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13240713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Erenumab on Patient-Reported Outcomes in Episodic Migraine in Asia, the Middle East, and Latin America: Results From the EMPOwER Study.","authors":"Shuu-Jiun Wang, Artemio A Roxas, Bibiana Saravia, Byung Kun Kim, Debashish Chowdhury, Naji J Riachi, Mei-Ling Sharon Tai, Surat Tanprawate, Tai Ngoc Tran, Yi Jing Zhao, Wendy Su, Shihua Wen, Subhayan Mondal, Laurent Ecochard, Michal Arkuszewski","doi":"10.1212/CPJ.0000000000200565","DOIUrl":"10.1212/CPJ.0000000000200565","url":null,"abstract":"<p><strong>Background and objectives: </strong>Migraine is a significant disabling neurologic headache disorder globally. Evaluating patient-related outcomes (PROs) is necessary to assess the impact of therapeutic interventions in preventive therapy. An exploratory analysis of data from the EMPOwER study examined the effect of erenumab on PROs in patients with episodic migraine (EM) in regions underrepresented in the pivotal Phase 3 trials of erenumab, specifically Asia, the Middle East, and Latin America.</p><p><strong>Methods: </strong>Patients (N = 900) were randomized (2:3:3) to receive monthly subcutaneous injections of erenumab 140 mg, erenumab 70 mg, or placebo. Adjusted mean changes from baseline in the Headache Impact Test (HIT-6), Migraine Physical Function Impact Diary (MPFID), modified Migraine Disability Assessment (mMIDAS), and EuroQoL 5-dimension 5-level scale (EQ-5D-5L) scores were assessed during the double-blind treatment phase of 3 months.</p><p><strong>Results: </strong>A statistically significant reduction from baseline in the HIT-6 total score was observed for erenumab 140 mg (-9.34, <i>p</i> < 0.001) and 70 mg (-8.39, <i>p</i> = 0.004) vs placebo (-6.62) at Month 3. Improvement in MPFID scores was also greater in the erenumab groups vs the placebo group (Everyday Activity: 140 mg, -5.61 [<i>p</i> = 0.002]; 70 mg, -4.94 [<i>p</i> = 0.011]; placebo, -3.19; Physical Impairment: 140 mg, -4.27 [<i>p</i> = 0.014]; 70 mg, -3.95 [<i>p</i> = 0.021]; placebo, -2.31) at Month 3. Similar findings were observed for mMIDAS scores (140 mg -8.99 [<i>p</i> < 0.001], 70 mg -8.11 [<i>p</i> = 0.011] vs placebo [-6.59]) and the EQ-5D-5L quality-of-life visual analog scale scores (140 mg 8.13 [<i>p</i> = 0.017], 70 mg 7.08 [<i>p</i> = 0.088] vs placebo [5.22]), although no meaningful between-group difference was noted for index values.</p><p><strong>Discussion: </strong>Erenumab showed favorable effects on PROs when compared with placebo in patients with EM. These results enhance the evidence for erenumab as an effective preventive therapy for patients with EM.</p><p><strong>Trial registration information: </strong>Clinicaltrials.gov/study/NCT03333109.</p>","PeriodicalId":19136,"journal":{"name":"Neurology. Clinical practice","volume":"16 2","pages":"e200565"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12867334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Outcomes in Antibody-Negative Autoimmune Encephalitis: A Systematic Review and Meta-Analysis.","authors":"Prachi Mohapatra, Meena Chandu, Pradeep Kumar, Rajesh Kumar Singh, Deepti Vibha, Manjari Tripathi","doi":"10.1212/CPJ.0000000000200602","DOIUrl":"10.1212/CPJ.0000000000200602","url":null,"abstract":"<p><strong>Purpose of review: </strong>Seronegative autoimmune encephalitis (AE), characterized by the absence of known neuronal autoantibodies despite meeting clinical criteria, presents significant diagnostic and therapeutic challenges. Although immunotherapy is frequently used, long-term outcomes in this population remain poorly characterized. This systematic review and meta-analysis aims to synthesize evidence on long-term outcomes in seronegative AE, focusing on functional status, seizure burden, cognitive impairment, relapses, immunotherapy practices, and prognostic indicators. We included studies involving patients 12 years or older diagnosed with antibody-negative probable AE (ANPRA), possible AE, or definite limbic encephalitis (LE) with negative neuronal antibodies according to Graus et al. (2016), with a minimum median follow-up of 6 months.</p><p><strong>Recent findings: </strong>Nineteen studies, predominantly retrospective cohorts with moderate risk of bias, met the inclusion criteria. The pooled proportion of patients achieving favorable functional outcomes (modified Rankin Scale 0-2) was 65% (95% CI 51% - 78%; <i>I</i>² = 88.1%; 12 studies, n = 782). Outcomes differed by seronegative subtype, with better functional recovery in seronegative LE (73%; 95% CI 45%-90%; 6 studies, n = 95) compared with ANPRA (47%; 95% CI 38%-55%; 5 studies, n = 277; <i>p</i> = 0.005). When compared with seropositive AE (n = 466), seronegative patients (n = 373) demonstrated comparable odds of favorable functional outcomes (odds ratio 0.50; 95% CI 0.19-1.31; <i>p</i> = 0.16) but had a significantly higher risk of persistent seizures (risk ratio 1.66; 95% CI 1.01-2.72; <i>p</i> = 0.04). The pooled relapse proportion among seronegative patients was 17% (95% CI 11%-26%; 7 studies, n = 350), with no significant difference by serostatus. Residual disability assessed using the Clinical Assessment Scale in Autoimmune Encephalitis suggested mild persistent impairment (mean score 3.11; 95% CI 1.79-4.43; 5 studies, n = 409). Owing to heterogeneity and inconsistent reporting, meta-analysis of cognitive outcomes, immunotherapy strategies, and RAPID (Refractory status epilepticus, Age ≥ 60 years, Probable AE, Infratentorial involvement, Delayed immunotherapy ≥ 1 month) scores was not feasible; narrative synthesis suggested persistent cognitive deficits and lower utilization of second-line immunotherapy in seronegative cohorts.</p><p><strong>Summary: </strong>Seronegative AE is associated with heterogeneous outcomes, with antibody-negative LE demonstrating better recovery than ANPRA. Subtype-specific variability and elevated seizure burden highlight the need for individualized management, timely diagnosis, structured follow-up, and well-designed prospective research.</p>","PeriodicalId":19136,"journal":{"name":"Neurology. Clinical practice","volume":"16 2","pages":"e200602"},"PeriodicalIF":3.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13240712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148265440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biosimilar Therapeutics Substitution: American Academy of Neurology Position Statement.","authors":"Jonathan D Santoro, Jonathan Crowe, Cale H Coppage, Emily Klatte, Benjamin Tolchin, Claire Riley, David A Evans, A Gordon Smith","doi":"10.1212/CPJ.0000000000200574","DOIUrl":"10.1212/CPJ.0000000000200574","url":null,"abstract":"<p><p>Biologic therapeutics have revolutionized treatment of disorders for which there were previously limited options. Biologic products are typically very expensive. However, the emergence of biosimilars (a biologic product that is nearly identical to a Food and Drug Administration [FDA]-approved \"branded\" version) offers an opportunity to reduce costs after the branded product's period of patent protection ends. Despite the promise of biosimilars, some physicians have expressed concern regarding interchangeability, especially in specific patient populations. The American Academy of Neurology (AAN) supports the cost-saving potential of biosimilar therapeutics while emphasizing the importance of a balance between reducing costs, maintaining clinical efficacy, and preserving the integrity of the physician-patient relationship. This position statement from the AAN offers a framework to aid neurologists in deciding whether to switch a patient from a branded biologic product to a biosimilar therapeutic. This framework aligns with broader AAN policies on drug pricing and medical decision-making autonomy.</p>","PeriodicalId":19136,"journal":{"name":"Neurology. Clinical practice","volume":"16 2","pages":"e200574"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12802970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145990190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling Narcolepsy: A Series of Complex Pediatric Cases.","authors":"Martina Gnazzo, Giulia Pisanò, Valentina Baldini, Francesca Citeroni, Francesco Canulli, Diana De Ronchi, Fabio Pizza, Giuseppe Plazzi","doi":"10.1212/CPJ.0000000000200583","DOIUrl":"10.1212/CPJ.0000000000200583","url":null,"abstract":"<p><strong>Objectives: </strong>Narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2) are rare, chronic neurologic disorders of hypersomnolence. Narcolepsy type 1 results from the selective loss of orexin-producing neurons, leading to markedly reduced levels of orexin neuropeptides in the brain and CSF. NT2 shares some symptoms with the former but has no orexin deficiency. Both disorders manifest as a spectrum of debilitating symptoms, including excessive daytime sleepiness (EDS), cataplexy (NT1 only), fragmented nocturnal sleep, sleep paralysis, and hallucinations. Diagnosis is particularly challenging, especially in pediatric patients.</p><p><strong>Methods: </strong>We describe 7 pediatric patients presenting with complex narcolepsy phenotype of EDS or cataplexy with a diverse array of comorbid genetic, neurologic, and neuropsychiatric conditions.</p><p><strong>Results: </strong>These cases illustrate the diagnostic challenges in differentiating \"primary narcolepsy\" from \"narcolepsy because of a medical disorder\" (e.g., Prader-Willi Syndrome) or \"narcolepsy associated with autism spectrum disorder or very early-onset schizophrenia.\" The patients underwent a comprehensive diagnostic workup, including polysomnography, multiple sleep latency testing (performed after wash-out of concomitant medications), brain magnetic resonance imaging, CSF hypocretin-1 assay, and, in case of consistent clues, autoimmune, and genetic testing.</p><p><strong>Discussion: </strong>Ensuring accurate and prompt narcolepsy diagnosis allows effective and patient-centered management.</p>","PeriodicalId":19136,"journal":{"name":"Neurology. Clinical practice","volume":"16 2","pages":"e200583"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12885170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Practical Management of Progressive Multifocal Leukoencephalopathy and Immune Reconstitution Inflammatory Syndrome.","authors":"Guillaume Martin-Blondel, Busranur Agac, Irene Cortese","doi":"10.1212/CPJ.0000000000200594","DOIUrl":"10.1212/CPJ.0000000000200594","url":null,"abstract":"<p><strong>Purpose of review: </strong>The aim of this narrative review was to provide treating physicians with practical guidance on the management of progressive multifocal leukoencephalopathy (PML), offering a rational, evidence-informed approach to diagnosis and treatment based on published literature and the authors' collective clinical experience.</p><p><strong>Recent findings: </strong>The management of PML requires precise characterization of disease status at presentation and throughout follow-up. We begin by outlining the clinical scenarios in which PML should be suspected, emphasizing that disease presentation is shaped by the strength and quality of the host's antiviral immune response. We then detail the evaluation of patients at the time of diagnosis and during follow-up, with particular attention to defining whether PML is presenting in its classic form, with inflammatory features, or in the context of immune reconstitution inflammatory syndrome. This assessment should incorporate prognostic markers to evaluate the potential for immune recovery and virologic control. We further summarize the current standard of care and identify clinical contexts in which experimental immunotherapeutic interventions to facilitate restoration of JC virus-specific immune functions may be considered, emphasizing the importance of individualized, risk-benefit-based decision making. Notably, such experimental immunotherapies are likely unnecessary and may even be harmful, once immune reconstitution has already been achieved and virologic control is evident. Finally, we address the management of inflammation in PML, underscoring that not all inflammatory presentations warrant corticosteroid therapy.</p><p><strong>Summary: </strong>The management of PML remains a significant clinical challenge. Standardizing assessment protocols across centers may enhance data quality and comparability and facilitate future collaborative and data-sharing efforts.</p>","PeriodicalId":19136,"journal":{"name":"Neurology. Clinical practice","volume":"16 2","pages":"e200594"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12885572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}