Pub Date : 2026-02-10Epub Date: 2025-12-31DOI: 10.1212/WNL.0000000000214564
Antonio Cabrera Muras, Juan José Gómez Muga, Lander Antón Méndez, Juan Carlos Garcia-Monco
{"title":"Teaching NeuroImage: Acquired Midbrain Cleft in a Professional Boxer.","authors":"Antonio Cabrera Muras, Juan José Gómez Muga, Lander Antón Méndez, Juan Carlos Garcia-Monco","doi":"10.1212/WNL.0000000000214564","DOIUrl":"https://doi.org/10.1212/WNL.0000000000214564","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"106 3","pages":"e214564"},"PeriodicalIF":8.5,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-10Epub Date: 2026-01-08DOI: 10.1212/WNL.0000000000210312
Jian Huang
{"title":"Reader Response: Tenecteplase vs Alteplase in Acute Ischemic Stroke Within 4.5 Hours: A Systematic Review and Meta-Analysis of Randomized Trials.","authors":"Jian Huang","doi":"10.1212/WNL.0000000000210312","DOIUrl":"https://doi.org/10.1212/WNL.0000000000210312","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"106 3","pages":"e210312"},"PeriodicalIF":8.5,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145934474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-10Epub Date: 2026-01-08DOI: 10.1212/WNL.0000000000214622
Alexander German, Alexander Grotemeyer, Veit Rothhammer, Arnd Doerfler, Juergen Winkler, Martin Regensburger
We present a case of reversible leukoencephalopathy and parkinsonism associated with type III mixed cryoglobulinemic vasculitis in a patient who initially presented with systemic vasculitic symptoms such as rash and arthralgias. Neither hepatitis C nor monoclonal gammopathy-typical triggers of cryoglobulinemia-was identified. The neurologic syndrome evolved with tremor, rigidity, significant cognitive decline, and extensive white matter abnormalities on MRI, mimicking primary neurodegenerative conditions such as multiple system atrophy. Diagnostic workup ruled out infectious, metabolic, autoimmune, and drug-related etiologies. After immunosuppressive therapy with methotrexate and steroids, the patient experienced marked clinical and radiologic improvement, paralleled by a decline in serum neurofilament levels. This case highlights the importance of recognizing inflammatory CNS involvement as a potentially reversible cause of rapidly progressive parkinsonism and cognitive impairment. Prompt identification and timely immunosuppressive treatment may reverse symptoms and prevent permanent neurologic damage.
{"title":"Pearls & Oy-sters: Reversible Leukoencephalopathy and Parkinsonism Due to CNS Involvement in Cryoglobulinemia.","authors":"Alexander German, Alexander Grotemeyer, Veit Rothhammer, Arnd Doerfler, Juergen Winkler, Martin Regensburger","doi":"10.1212/WNL.0000000000214622","DOIUrl":"https://doi.org/10.1212/WNL.0000000000214622","url":null,"abstract":"<p><p>We present a case of reversible leukoencephalopathy and parkinsonism associated with type III mixed cryoglobulinemic vasculitis in a patient who initially presented with systemic vasculitic symptoms such as rash and arthralgias. Neither hepatitis C nor monoclonal gammopathy-typical triggers of cryoglobulinemia-was identified. The neurologic syndrome evolved with tremor, rigidity, significant cognitive decline, and extensive white matter abnormalities on MRI, mimicking primary neurodegenerative conditions such as multiple system atrophy. Diagnostic workup ruled out infectious, metabolic, autoimmune, and drug-related etiologies. After immunosuppressive therapy with methotrexate and steroids, the patient experienced marked clinical and radiologic improvement, paralleled by a decline in serum neurofilament levels. This case highlights the importance of recognizing inflammatory CNS involvement as a potentially reversible cause of rapidly progressive parkinsonism and cognitive impairment. Prompt identification and timely immunosuppressive treatment may reverse symptoms and prevent permanent neurologic damage.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"106 3","pages":"e214622"},"PeriodicalIF":8.5,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145934544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We report the case of a 27-year-old man with a history of speech delay and chronic, progressive movement disorder. He first developed gait difficulty at the age of 12. Given clinical signs of bradykinesia and resting tremor, he received a clinical diagnosis of childhood-onset parkinsonism. Treatment with oral levodopa initially improved symptoms, but after 2 years, he developed motor fluctuations and dyskinesias. Additional signs of spasticity and brain MRI showing a thin corpus callosum prompted genetic testing that identified a heterozygous pathogenic variant in the PRKN gene. However, he exhibited a progressive loss of response to chronic dopaminergic therapy, first with oral and later with continuous levodopa-carbidopa intestinal gel infusion, with disease progression over 7 years. This progression led to further genetic testing and the diagnosis of hereditary spastic paraplegia type 15 (SPG 15). Advancing motor symptoms prompted deep brain stimulation and botulinum toxin injections, although these had limited benefit. This case highlights the challenges of diagnosing and managing juvenile-onset parkinsonism and the value of comprehensive genetic analysis in evaluating genotypic-phenotypic correlations. Hereditary spastic paraplegias (HSPs) are a rare group of neurodegenerative disorders with diverse clinical and genetic features. They can be inherited in autosomal dominant, recessive, X-linked, or mitochondrial patterns. The SPG15 subtype (or HSP-ZFYVE26), caused by pathogenic variants in the ZFYVE26 gene, is a common form of autosomal recessive HSP. Presenting symptoms vary but commonly include cognitive impairment with a history of speech delay or learning disability and balance impairment or clumsiness from spasticity of the lower limbs.
{"title":"Pearls & Oy-sters: Hereditary Spastic Paraplegia Type 15 Presenting as Juvenile Onset Levodopa-Responsive Parkinsonism.","authors":"Abhilash Thatikala, Aditya Vikram Boddu, Divya Nayar, Tuhin Virmani","doi":"10.1212/WNL.0000000000214514","DOIUrl":"https://doi.org/10.1212/WNL.0000000000214514","url":null,"abstract":"<p><p>We report the case of a 27-year-old man with a history of speech delay and chronic, progressive movement disorder. He first developed gait difficulty at the age of 12. Given clinical signs of bradykinesia and resting tremor, he received a clinical diagnosis of childhood-onset parkinsonism. Treatment with oral levodopa initially improved symptoms, but after 2 years, he developed motor fluctuations and dyskinesias. Additional signs of spasticity and brain MRI showing a thin corpus callosum prompted genetic testing that identified a heterozygous pathogenic variant in the PRKN gene. However, he exhibited a progressive loss of response to chronic dopaminergic therapy, first with oral and later with continuous levodopa-carbidopa intestinal gel infusion, with disease progression over 7 years. This progression led to further genetic testing and the diagnosis of hereditary spastic paraplegia type 15 (SPG 15). Advancing motor symptoms prompted deep brain stimulation and botulinum toxin injections, although these had limited benefit. This case highlights the challenges of diagnosing and managing juvenile-onset parkinsonism and the value of comprehensive genetic analysis in evaluating genotypic-phenotypic correlations. Hereditary spastic paraplegias (HSPs) are a rare group of neurodegenerative disorders with diverse clinical and genetic features. They can be inherited in autosomal dominant, recessive, X-linked, or mitochondrial patterns. The SPG15 subtype (or HSP-<i>ZFYVE26)</i>, caused by pathogenic variants in the <i>ZFYVE26</i> gene, is a common form of autosomal recessive HSP. Presenting symptoms vary but commonly include cognitive impairment with a history of speech delay or learning disability and balance impairment or clumsiness from spasticity of the lower limbs.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"106 3","pages":"e214514"},"PeriodicalIF":8.5,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145934556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-30DOI: 10.1212/wnl.0000000000214720
Anup D Patel,Neil Kulkarni
{"title":"SUDEP Awareness: A Gulf Neurologists Must Cross.","authors":"Anup D Patel,Neil Kulkarni","doi":"10.1212/wnl.0000000000214720","DOIUrl":"https://doi.org/10.1212/wnl.0000000000214720","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 1","pages":"e214720"},"PeriodicalIF":9.9,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-30DOI: 10.1212/wnl.0000000000213380
Anna Ranta
{"title":"Author Response: The Time Has Come. The Time Is Now. IV Alteplase, Will You Please Go Now?","authors":"Anna Ranta","doi":"10.1212/wnl.0000000000213380","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213380","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"30 1","pages":"e213380"},"PeriodicalIF":9.9,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-30DOI: 10.1212/wnl.0000000000213342
Steven H Horowitz
{"title":"Reader Response: The Time Has Come. The Time Is Now. IV Alteplase, Will You Please Go Now?","authors":"Steven H Horowitz","doi":"10.1212/wnl.0000000000213342","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213342","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"191 1","pages":"e213342"},"PeriodicalIF":9.9,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-30DOI: 10.1212/wnl.0000000000214623
Itay Tokatly Latzer,Daniel Friedman,David N Williams,Gardiner Lapham,Alison Kukla,Orit Karnieli-Miller,Phillip L Pearl
BACKGROUND AND OBJECTIVESSudden unexpected death in epilepsy (SUDEP) is the leading cause of seizure-related deaths in people with epilepsy. Despite evidence that SUDEP counseling does not cause stress, improves treatment adherence, and empowers people with epilepsy and their caregivers, it remains underdiscussed. This study aimed to explore the in-depth perspectives of parents who have lost a child to SUDEP, focusing on their experiences, grief, and coping strategies, while factoring in their demographics, the clinical features of their deceased children, and their previous awareness of SUDEP, all aspects that have not been systematically investigated before.METHODSThis qualitative phenomenological study involved in-depth semistructured interviews with 51 parents of 43 children who died of SUDEP. Transcripts were analyzed using immersion/crystallization qualitative methodology with Dedoose software, using an iterative consensus-building process. Thematic analysis revealed common perspectives, grief narratives, coping strategies, and perceived needs among parents after their child's SUDEP.RESULTSOf the 51 participating parents (mean age 54.1 ± 9.4 years, 71% female), 27 reported being unaware of SUDEP before it occurred, whereas 24 reported previous awareness of it. These groups shared similar demographics and clinical characteristics. However, "unaware" parents expressed more intense trauma and prolonged maladaptive grief, characterized by guilt, extreme anger, and medical distrust. By contrast, "aware" parents described mitigated trauma, with less guilt- and anger-ridden grief, and reduced reliance on specialized support groups. Previous SUDEP awareness provided emotional preparation, buffering the devastating reality and fostering agency and acceptance. Another theme highlighted the struggles parents faced immediately after SUDEP, particularly with law enforcement and treating physicians. Unanimously, parents emphasized the paramount importance of counseling about the known relationship between epilepsy and SUDEP.DISCUSSIONPrevious awareness of SUDEP (or lack thereof) has complex and far-reaching effects on the subsequent parental perceived trauma, grief, and coping processes. Furthermore, emergency responders, official personnel, and treating physicians may mishandle the aftermath of SUDEP. This study's findings strongly advocate for a paradigm shift in SUDEP-related practices across multiple disciplines, including legislation. Emphasis should be placed on increasing proactive SUDEP counseling to mitigate the traumatic effect and subsequent grieving process when SUDEP occurs.
{"title":"SUDEP Awareness and Effect on Parental Trauma, Grief, and Coping After the Death of a Child: A Qualitative Investigation.","authors":"Itay Tokatly Latzer,Daniel Friedman,David N Williams,Gardiner Lapham,Alison Kukla,Orit Karnieli-Miller,Phillip L Pearl","doi":"10.1212/wnl.0000000000214623","DOIUrl":"https://doi.org/10.1212/wnl.0000000000214623","url":null,"abstract":"BACKGROUND AND OBJECTIVESSudden unexpected death in epilepsy (SUDEP) is the leading cause of seizure-related deaths in people with epilepsy. Despite evidence that SUDEP counseling does not cause stress, improves treatment adherence, and empowers people with epilepsy and their caregivers, it remains underdiscussed. This study aimed to explore the in-depth perspectives of parents who have lost a child to SUDEP, focusing on their experiences, grief, and coping strategies, while factoring in their demographics, the clinical features of their deceased children, and their previous awareness of SUDEP, all aspects that have not been systematically investigated before.METHODSThis qualitative phenomenological study involved in-depth semistructured interviews with 51 parents of 43 children who died of SUDEP. Transcripts were analyzed using immersion/crystallization qualitative methodology with Dedoose software, using an iterative consensus-building process. Thematic analysis revealed common perspectives, grief narratives, coping strategies, and perceived needs among parents after their child's SUDEP.RESULTSOf the 51 participating parents (mean age 54.1 ± 9.4 years, 71% female), 27 reported being unaware of SUDEP before it occurred, whereas 24 reported previous awareness of it. These groups shared similar demographics and clinical characteristics. However, \"unaware\" parents expressed more intense trauma and prolonged maladaptive grief, characterized by guilt, extreme anger, and medical distrust. By contrast, \"aware\" parents described mitigated trauma, with less guilt- and anger-ridden grief, and reduced reliance on specialized support groups. Previous SUDEP awareness provided emotional preparation, buffering the devastating reality and fostering agency and acceptance. Another theme highlighted the struggles parents faced immediately after SUDEP, particularly with law enforcement and treating physicians. Unanimously, parents emphasized the paramount importance of counseling about the known relationship between epilepsy and SUDEP.DISCUSSIONPrevious awareness of SUDEP (or lack thereof) has complex and far-reaching effects on the subsequent parental perceived trauma, grief, and coping processes. Furthermore, emergency responders, official personnel, and treating physicians may mishandle the aftermath of SUDEP. This study's findings strongly advocate for a paradigm shift in SUDEP-related practices across multiple disciplines, including legislation. Emphasis should be placed on increasing proactive SUDEP counseling to mitigate the traumatic effect and subsequent grieving process when SUDEP occurs.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"2 1","pages":"e214623"},"PeriodicalIF":9.9,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-30DOI: 10.1212/wnl.0000000000214611
Roy H Hamilton
Noninvasive brain stimulation (NIBS) has emerged as a transformative tool in both cognitive neuroscience research and the treatment of a growing range of neuropsychiatric conditions. This commentary, based on the 2025 H. Houston Merritt Lecture, explores how NIBS can be applied within a translational cognitive neuroscience framework that bridges theoretical models of cognitive function with targeted neural interventions. Drawing on over 15 years of research, the major focus of this piece is on the use of transcranial magnetic stimulation (TMS) to characterize and enhance language function in persons with aphasia (PWA). A significant body of work has examined the role of the right hemisphere, particularly the right pars triangularis, which may exert a maladaptive influence within reorganized language networks in many PWA. Inhibitory TMS targeting this region has been shown to produce both transient and sustained improvements in language performance. Key predictors of response to TMS include the characteristics of participants' language deficits and genetic differences that influence neuroplasticity. Network neuroscience approaches can also enhance predictive accuracy by revealing how individual variations in brain structure influence stimulation outcomes. While TMS remains the most extensively studied NIBS modality, transcranial electrical stimulation is gaining momentum, with promising results in both poststroke and primary progressive aphasia. Emerging modalities such as focused ultrasound and transcranial temporal interference stimulation are also on the rise as tools for enhancing brain performance. However, the expanding use of NIBS also raises ethical considerations that must be addressed to ensure its equitable and responsible deployment. Ultimately, NIBS represents a powerful convergence of neuroscience and technology, offering renewed hope for restoring cognitive function in individuals affected by neurologic disease.
{"title":"Noninvasive Brain Stimulation in Translational Cognitive Neuroscience-Applications in Aphasia and Beyond: 2025 H. Houston Merritt Award Lecture.","authors":"Roy H Hamilton","doi":"10.1212/wnl.0000000000214611","DOIUrl":"https://doi.org/10.1212/wnl.0000000000214611","url":null,"abstract":"Noninvasive brain stimulation (NIBS) has emerged as a transformative tool in both cognitive neuroscience research and the treatment of a growing range of neuropsychiatric conditions. This commentary, based on the 2025 H. Houston Merritt Lecture, explores how NIBS can be applied within a translational cognitive neuroscience framework that bridges theoretical models of cognitive function with targeted neural interventions. Drawing on over 15 years of research, the major focus of this piece is on the use of transcranial magnetic stimulation (TMS) to characterize and enhance language function in persons with aphasia (PWA). A significant body of work has examined the role of the right hemisphere, particularly the right pars triangularis, which may exert a maladaptive influence within reorganized language networks in many PWA. Inhibitory TMS targeting this region has been shown to produce both transient and sustained improvements in language performance. Key predictors of response to TMS include the characteristics of participants' language deficits and genetic differences that influence neuroplasticity. Network neuroscience approaches can also enhance predictive accuracy by revealing how individual variations in brain structure influence stimulation outcomes. While TMS remains the most extensively studied NIBS modality, transcranial electrical stimulation is gaining momentum, with promising results in both poststroke and primary progressive aphasia. Emerging modalities such as focused ultrasound and transcranial temporal interference stimulation are also on the rise as tools for enhancing brain performance. However, the expanding use of NIBS also raises ethical considerations that must be addressed to ensure its equitable and responsible deployment. Ultimately, NIBS represents a powerful convergence of neuroscience and technology, offering renewed hope for restoring cognitive function in individuals affected by neurologic disease.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"282 1","pages":"e214611"},"PeriodicalIF":9.9,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-30DOI: 10.1212/wnl.0000000000214739
Aravind Ganesh,Steven L Galetta
{"title":"Editors' Note: A Fond Farewell to Alteplase.","authors":"Aravind Ganesh,Steven L Galetta","doi":"10.1212/wnl.0000000000214739","DOIUrl":"https://doi.org/10.1212/wnl.0000000000214739","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"8 1","pages":"e214739"},"PeriodicalIF":9.9,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}