Brain communicationsPub Date : 2024-08-30eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae287
Marij Middag-van Spanje, Tanja C W Nijboer, Jan Schepers, Caroline van Heugten, Alexander T Sack, Teresa Schuhmann
{"title":"Alpha transcranial alternating current stimulation as add-on to neglect training: a randomized trial.","authors":"Marij Middag-van Spanje, Tanja C W Nijboer, Jan Schepers, Caroline van Heugten, Alexander T Sack, Teresa Schuhmann","doi":"10.1093/braincomms/fcae287","DOIUrl":"https://doi.org/10.1093/braincomms/fcae287","url":null,"abstract":"<p><p>Visuospatial neglect is a common and debilitating condition following unilateral stroke, significantly impacting cognitive functioning and daily life. There is an urgent need for effective treatments that can provide clinically relevant and sustained benefits. In addition to traditional stroke treatment, non-invasive brain stimulation, such as transcranial alternating current stimulation, shows promise as a complementary approach to enhance stroke recovery. In the current study, we aimed to evaluate the additive effects of multi-session transcranial alternating current stimulation at alpha frequency when combined with visual scanning training in chronic stroke patients with visuospatial neglect. In this double-blind randomized controlled trial, we compared the effects of active transcranial alternating current stimulation at alpha frequency to sham (placebo) transcranial alternating current stimulation, both combined with visual scanning training. Both groups received eighteen 40-minute training sessions over a 6-week period. A total of 22 chronic visuospatial neglect patients participated in the study (active group <i>n</i> = 12, sham group <i>n</i> = 10). The median age was 61.0 years, with a median time since stroke of 36.1 months. We assessed the patients at six time-points: at baseline, after the first, ninth and eighteenth training sessions, as well as 1 week and 3 months following the completion of the combined neuromodulation intervention. The primary outcome measure was the change in performance on a visual search task, specifically the star cancellation task. Secondary outcomes included performance on a visual detection task, two line bisection tasks and three tasks evaluating visuospatial neglect in daily living. We found significantly improved visual search (primary outcome) and visual detection performance in the neglected side in the active transcranial alternating current stimulation group, compared to the sham transcranial alternating current stimulation group. We did not observe stimulation effects on line bisection performance nor in daily living. Time effects were observed on all but one outcome measures. Multi-session transcranial alternating current stimulation combined with visual scanning training may be a more effective treatment for chronic visuospatial neglect than visual scanning training alone. These findings provide valuable insights into novel strategies for stroke recovery, even long after the injury, with the aim of enhancing cognitive rehabilitation outcomes and improving the overall quality of life for individuals affected by this condition. <b>Trial registration</b>: ClinicalTrials.gov; registration number: NCT05466487; https://clinicaltrials.gov/ct2/show/NCT05466487.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303359","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}
Brain communicationsPub Date : 2024-08-30eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae293
Julie Petersen, Josh McGough, Georgia Gopinath, Nadia Scantlebury, Richa Tripathi, Cheryl Brandmeir, Silina Z Boshmaf, Nicholas J Brandmeir, Isabella J Sewell, Peter E Konrad, Agessandro Abrahao, Ann Murray, Benjamin Lam, Manish Ranjan, Clement Hamani, Jessica Frey, Camryn Rohringer, Melissa McSweeney, James J Mahoney, Michael L Schwartz, Ali Rezai, Nir Lipsman, David M Scarisbrick, Jennifer S Rabin
{"title":"Cognitive outcomes following unilateral magnetic resonance-guided focused ultrasound thalamotomy for essential tremor: findings from two cohorts.","authors":"Julie Petersen, Josh McGough, Georgia Gopinath, Nadia Scantlebury, Richa Tripathi, Cheryl Brandmeir, Silina Z Boshmaf, Nicholas J Brandmeir, Isabella J Sewell, Peter E Konrad, Agessandro Abrahao, Ann Murray, Benjamin Lam, Manish Ranjan, Clement Hamani, Jessica Frey, Camryn Rohringer, Melissa McSweeney, James J Mahoney, Michael L Schwartz, Ali Rezai, Nir Lipsman, David M Scarisbrick, Jennifer S Rabin","doi":"10.1093/braincomms/fcae293","DOIUrl":"https://doi.org/10.1093/braincomms/fcae293","url":null,"abstract":"<p><p>Magnetic resonance-guided, focused ultrasound thalamotomy is a neurosurgical treatment for refractory essential tremor. This study examined cognitive outcomes following unilateral magnetic resonance-guided, focused ultrasound thalamotomy, targeting the ventral intermediate nucleus of the thalamus for essential tremor. The research was conducted at two sites: Sunnybrook Research Institute in Toronto, Canada, and West Virginia University School of Medicine Rockefeller Neuroscience Institute in West Virginia, USA. The study focused on cognitive changes at both the group and individual levels. Patients with refractory essential tremor completed cognitive testing before and after magnetic resonance-guided, focused ultrasound thalamotomy at both sites. The cognitive testing assessed domains of attention, processing speed, working memory, executive function, language and learning/memory. Postoperative changes in cognition were examined using paired <i>t</i>-tests and Wilcoxon signed-rank tests, as appropriate. Reliable change indices were calculated to assess clinically significant changes at the individual level. A total of 33 patients from Toronto and 22 patients from West Virginia were included. Following magnetic resonance-guided, focused ultrasound thalamotomy, there was a significant reduction in tremor severity in both cohorts. At the group level, there were no significant declines in postoperative cognitive performance in either cohort. The reliable change analyses revealed some variability at the individual level, with most patients maintaining stable performance or showing improvement. Taken together, the results from these two independent cohorts demonstrate that unilateral magnetic resonance-guided, focused ultrasound thalamotomy significantly reduces tremor severity without negatively impacting cognition at both the group and individual levels, highlighting the cognitive safety of magnetic resonance-guided focused ultrasound thalamotomy for essential tremor.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303378","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}
Brain communicationsPub Date : 2024-08-30eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae295
Paweł Jakuszyk, Aleksandra Podlecka-Piętowska, Bartosz Kossowski, Monika Nojszewska, Beata Zakrzewska-Pniewska, Maciej Juryńczyk
{"title":"Patterns of cerebral damage in multiple sclerosis and aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders-major differences revealed by non-conventional imaging.","authors":"Paweł Jakuszyk, Aleksandra Podlecka-Piętowska, Bartosz Kossowski, Monika Nojszewska, Beata Zakrzewska-Pniewska, Maciej Juryńczyk","doi":"10.1093/braincomms/fcae295","DOIUrl":"https://doi.org/10.1093/braincomms/fcae295","url":null,"abstract":"<p><p>Multiple sclerosis and aquaporin-4 antibody neuromyelitis optica spectrum disorders are distinct autoimmune CNS disorders with overlapping clinical features but differing pathology. Multiple sclerosis is primarily a demyelinating disease with the presence of widespread axonal damage, while neuromyelitis optica spectrum disorders is characterized by astrocyte injury with secondary demyelination. Diagnosis is typically based on lesion characteristics observed on standard MRI imaging and antibody testing but can be challenging in patients with in-between clinical presentations. Non-conventional MRI techniques can provide valuable diagnostic information by measuring disease processes at the microstructural level. We used non-conventional MRI to measure markers of axonal loss in specific white matter tracts in multiple sclerosis and neuromyelitis optica spectrum disorders, depending on their relationship with focal lesions. Patients with relapsing-remitting multiple sclerosis (<i>n</i> = 20), aquaporin-4 antibody-associated neuromyelitis optica spectrum disorders (<i>n</i> = 20) and healthy controls (<i>n</i> = 20) underwent a 3T brain MRI, including T<sub>1</sub>-, T<sub>2</sub>- and diffusion-weighted sequences, quantitative susceptibility mapping and phase-sensitive inversion recovery sequence. Tractometry was used to differentiate tract fibres traversing through white matter lesions from those that did not. Neurite density index was assessed using neurite orientation dispersion and density imaging model. Cortical damage was evaluated using T<sub>1</sub> relaxation rates. Cortical lesions and paramagnetic rim lesions were identified using phase-sensitive inversion recovery and quantitative susceptibility mapping. In tracts traversing lesions, only one out of 50 tracts showed a decreased neurite density index in multiple sclerosis compared with neuromyelitis optica spectrum disorders. Among 50 tracts not traversing lesions, six showed reduced neurite density in multiple sclerosis (including three in the cerebellum and brainstem) compared to neuromyelitis optica spectrum disorders. In multiple sclerosis, reduced neurite density was found in the majority of fibres traversing (40/50) and not traversing (37/50) white matter lesions when compared to healthy controls. A negative correlation between neurite density in lesion-free fibres and cortical lesions, but not paramagnetic rim lesions, was observed in multiple sclerosis (39/50 tracts). In neuromyelitis optica spectrum disorders compared to healthy controls, decreased neurite density was observed in a subset of fibres traversing white matter lesions, but not in lesion-free fibres. In conclusion, we identified significant differences between multiple sclerosis and neuromyelitis optica spectrum disorders corresponding to their distinct pathologies. Specifically, in multiple sclerosis, neurite density reduction was widespread across fibres, regardless of their relationship to white matter lesions, ","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303344","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}
Brain communicationsPub Date : 2024-08-28eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae290
Anna Rennie, Urban Ekman, Sara Shams, Lina Rydén, Jessica Samuelsson, Anna Zettergren, Silke Kern, Ketil Oppedal, Frédéric Blanc, Jakub Hort, Sara Garcia-Ptacek, Angelo Antonini, Afina W Lemstra, Alessandro Padovani, Milica Gregoric Kramberger, Irena Rektorová, Zuzana Walker, Jón Snædal, Matteo Pardini, John-Paul Taylor, Laura Bonanni, Tobias Granberg, Dag Aarsland, Ingmar Skoog, Lars-Olof Wahlund, Miia Kivipelto, Eric Westman, Daniel Ferreira
{"title":"Cerebrovascular and Alzheimer's disease biomarkers in dementia with Lewy bodies and other dementias.","authors":"Anna Rennie, Urban Ekman, Sara Shams, Lina Rydén, Jessica Samuelsson, Anna Zettergren, Silke Kern, Ketil Oppedal, Frédéric Blanc, Jakub Hort, Sara Garcia-Ptacek, Angelo Antonini, Afina W Lemstra, Alessandro Padovani, Milica Gregoric Kramberger, Irena Rektorová, Zuzana Walker, Jón Snædal, Matteo Pardini, John-Paul Taylor, Laura Bonanni, Tobias Granberg, Dag Aarsland, Ingmar Skoog, Lars-Olof Wahlund, Miia Kivipelto, Eric Westman, Daniel Ferreira","doi":"10.1093/braincomms/fcae290","DOIUrl":"https://doi.org/10.1093/braincomms/fcae290","url":null,"abstract":"<p><p>Co-pathologies are common in dementia with Lewy bodies and other dementia disorders. We investigated cerebrovascular and Alzheimer's disease co-pathologies in patients with dementia with Lewy bodies in comparison with patients with mild cognitive impairment, Alzheimer's disease, mixed dementia, vascular dementia or Parkinson's disease with dementia and cognitively unimpaired participants. We assessed the association of biomarkers of cerebrovascular and Alzheimer's disease co-pathologies with medial temporal atrophy and global cognitive performance. Additionally, we evaluated whether the findings were specific to dementia with Lewy bodies. We gathered a multi-cohort dataset of 4549 participants (dementia with Lewy bodies = 331, cognitively unimpaired = 1505, mild cognitive impairment = 1489, Alzheimer's disease = 708, mixed dementia = 268, vascular dementia = 148, Parkinson's disease with dementia = 120) from the MemClin Study, Karolinska Imaging in Dementia Study, Gothenburg H70 Birth Cohort Studies and the European DLB Consortium. Cerebrovascular co-pathology was assessed with visual ratings of white matter hyperintensities using the Fazekas scale through structural imaging. Alzheimer's disease biomarkers of β-amyloid and phosphorylated tau were assessed in the cerebrospinal fluid for a subsample (<i>N</i> = 2191). Medial temporal atrophy was assessed with visual ratings and global cognition with the mini-mental state examination. Differences and associations were assessed through regression models, including interaction terms. In dementia with Lewy bodies, 43% had a high white matter hyperintensity load, which was significantly higher than that in cognitively unimpaired (14%), mild cognitive impairment (26%) and Alzheimer's disease (27%), but lower than that in vascular dementia (62%). In dementia with Lewy bodies, white matter hyperintensities were associated with medial temporal atrophy, and the interaction term showed that this association was stronger than that in cognitively unimpaired and mixed dementia. However, the association between white matter hyperintensities and medial temporal atrophy was non-significant when β-amyloid was included in the model. Instead, β-amyloid predicted medial temporal atrophy in dementia with Lewy bodies, in contrast to the findings in mild cognitive impairment where medial temporal atrophy scores were independent of β-amyloid. Dementia with Lewy bodies had the lowest performance on global cognition, but this was not associated with white matter hyperintensities. In Alzheimer's disease, global cognitive performance was lower in patients with more white matter hyperintensities. We conclude that white matter hyperintensities are common in dementia with Lewy bodies and are associated with more atrophy in medial temporal lobes, but this association depended on β-amyloid-related pathology in our cohort. The associations between biomarkers were overall stronger in dementia with Lewy bodies than in some of th","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303376","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}
Brain communicationsPub Date : 2024-08-28eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae289
Lisette R M Raasing, Oscar J M Vogels, Mirjam Datema, Carmen A Ambarus, Martijn R Tannemaat, Jan C Grutters, Marcel Veltkamp
{"title":"New phenotyping questionnaire for diagnosing sarcoidosis-associated small fiber neuropathy.","authors":"Lisette R M Raasing, Oscar J M Vogels, Mirjam Datema, Carmen A Ambarus, Martijn R Tannemaat, Jan C Grutters, Marcel Veltkamp","doi":"10.1093/braincomms/fcae289","DOIUrl":"https://doi.org/10.1093/braincomms/fcae289","url":null,"abstract":"<p><p>Small fiber neuropathy is a common complication in patients with sarcoidosis and its prevalence is estimated at 40-86%. The underlying mechanism influences the presentation of small fiber neuropathy. For example, patients with metabolic diseases are often associated with a classic length-dependent small fiber neuropathy pattern, while patients with inflammatory diseases are more often present with a non-length-dependent small fiber neuropathy. Detailed phenotyping may be useful to improve diagnostic efficiency, as a clue to underlying mechanisms and as a precondition for personalized medicine. This study examined four phenotypes distinguishing between length-dependent and non-length-dependent presentation with a new subdivision for continuous and intermittent presentation. Forty-eight sarcoid patients with symptoms and at least two clinical signs of small fiber neuropathy and normal nerve conduction studies were classified as having probable small fiber neuropathy. A new small fiber neuropathy phenotyping questionnaire has been developed that allows patients to mark the anatomical locations of pain at three different levels: the skin, muscles, and joints. The location of symptoms was used to define length dependence, and two colors were used to distinguish continuous (red) from intermittent (blue) symptoms. In addition, skin biopsy, corneal confocal microscopy, Sudoscan and water immersion skin wrinkling were used to investigate a correlation between the four phenotypes, sensory function, nerve fiber density, and autonomic nerve function. Overall, 35% of patients with probable small fiber neuropathy showed length-dependent symptoms and 44% showed non-length-dependent symptoms while 21% suffered from non-neuropathic musculoskeletal pain. The distinction between intermittent and continuous symptoms showed significantly less continuous than intermittent non-length-dependent symptoms (odds ratio = 0.3, <i>P</i> = 0.01). Moreover, continuous length-dependent symptoms were the only phenotype that correlated with thermal threshold testing (<i>R</i> = 0.3; <i>P</i> = 0.02) and the small fiber neuropathy screening list (<i>R</i> = 0.3; <i>P</i> = 0.03). In addition, thermal threshold testing (TTT) also correlated with the small fiber neuropathy (SFN) screening list (<i>R</i> = 0.3; <i>P</i> = 0.03). Other diagnostic methods showed no correlation with any of the four defined phenotypes. A novel finding is that TTT is only associated with continuous length-dependent pain, suggesting that TTT could result in more false negatives in patients with other pain phenotypes. Determining the pathophysiologic mechanisms could help develop new diagnostic methods. If patients suspected of SFN show symptoms without a length-dependent continuous presentation, the diagnosis should focus less on the diagnostic methods used.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303343","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}
Brain communicationsPub Date : 2024-08-26eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae288
Maximilian Vidovic, Hanna Sophie Lapp, Constanze Weber, Lydia Plitzko, Michael Seifert, Petra Steinacker, Markus Otto, Andreas Hermann, René Günther
{"title":"Comparative analysis of neurofilaments and biomarkers of muscular damage in amyotrophic lateral sclerosis.","authors":"Maximilian Vidovic, Hanna Sophie Lapp, Constanze Weber, Lydia Plitzko, Michael Seifert, Petra Steinacker, Markus Otto, Andreas Hermann, René Günther","doi":"10.1093/braincomms/fcae288","DOIUrl":"10.1093/braincomms/fcae288","url":null,"abstract":"<p><p>Diagnosis of the fatal neurodegenerative disease amyotrophic lateral sclerosis is challenging. Neurofilaments, indicative of neuronal damage, along with creatine kinase, creatinine, myoglobin, and troponin T, representing muscular damage, have been identified as promising fluid biomarkers. This study aims to comprehensively assess and compare their diagnostic and prognostic potential in a 'real-world' cohort of patients with amyotrophic lateral sclerosis. About 77 patients with amyotrophic lateral sclerosis and its clinical variants, and 26 age- and sex-matched controls with various neuromuscular and neurodegenerative diseases, were retrospectively included in this monocentric, cross-sectional study. Neurofilaments in cerebrospinal fluid and biomarkers of muscular damage in serum were measured and correlated with demographic features, motor function, survival time, clinical phenotypes, and the extent of upper and lower motor neuron involvement. Neurofilament, myoglobin, and troponin T concentrations were higher in patients with amyotrophic lateral sclerosis compared to disease controls. Higher neurofilament levels correlated with lower motor function and faster disease progression rate, while higher creatine kinase and creatinine concentrations were linked to preserved motor function. In contrast, troponin T elevation indicated poorer fine and gross motor functions. Increased neurofilament levels were associated with shorter survival, whereas biomarkers of muscular damage lacked survival correlation. Neurofilament concentrations were higher in classical amyotrophic lateral sclerosis than in progressive muscular atrophy, while myoglobin and troponin T levels were elevated in progressive muscular atrophy compared to primary lateral sclerosis. Neurofilaments were predominantly linked to upper motor neuron involvement. Our findings confirmed the robust diagnostic and prognostic value of neurofilaments in amyotrophic lateral sclerosis. Elevated neurofilament concentrations were associated with higher disease severity, faster disease progression, shorter survival, and predominant upper motor neuron degeneration. Biomarkers of muscular damage were inferior in distinguishing amyotrophic lateral sclerosis from other neuromuscular and neurodegenerative diseases. However, they may serve as complementary biomarkers and support in discriminating clinical variants of amyotrophic lateral sclerosis.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142052","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}
Brain communicationsPub Date : 2024-08-26eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae286
Nicolaas I Bohnen, Uros Marusic, Stiven Roytman, Rebecca Paalanen, Fotini Michalakis, Taylor Brown, Peter J H Scott, Giulia Carli, Roger L Albin, Prabesh Kanel
{"title":"Dynamic balance and gait impairments in Parkinson's disease: novel cholinergic patterns.","authors":"Nicolaas I Bohnen, Uros Marusic, Stiven Roytman, Rebecca Paalanen, Fotini Michalakis, Taylor Brown, Peter J H Scott, Giulia Carli, Roger L Albin, Prabesh Kanel","doi":"10.1093/braincomms/fcae286","DOIUrl":"10.1093/braincomms/fcae286","url":null,"abstract":"<p><p>The cholinergic system has been implicated in postural deficits, in particular falls, in Parkinson's disease (PD). Falls and freezing of gait typically occur during dynamic and challenging balance and gait conditions, such as when initiating gait, experiencing postural perturbations, or making turns. However, the precise cholinergic neural substrate underlying dynamic postural and gait changes remains poorly understood. The aim of this study was to investigate whether brain vesicular acetylcholine transporter binding, as measured with [<sup>18</sup>F]-fluoroethoxybenzovesamicol binding PET, correlates with dynamic gait and balance impairments in 125 patients with PD (mean age 66.89 ± 7.71 years) using the abbreviated balance evaluation systems test total and its four functional domain sub-scores (anticipatory postural control, reactive postural control, dynamic gait, and sensory integration). Whole brain false discovery-corrected (<i>P</i> < 0.05) correlations for total abbreviated balance evaluation systems test scores included the following bilateral or asymmetric hemispheric regions: gyrus rectus, orbitofrontal cortex, anterior part of the dorsomedial prefrontal cortex, dorsolateral prefrontal cortex, cingulum, frontotemporal opercula, insula, fimbria, right temporal pole, mesiotemporal, parietal and visual cortices, caudate nucleus, lateral and medial geniculate bodies, thalamus, lingual gyrus, cerebellar hemisphere lobule VI, left cerebellar crus I, superior cerebellar peduncles, flocculus, and nodulus. No significant correlations were found for the putamen or anteroventral putamen. The four domain-specific sub-scores demonstrated overlapping cholinergic topography in the metathalamus, fimbria, thalamus proper, and prefrontal cortices but also showed distinct topographic variations. For example, reactive postural control functions involved the right flocculus but not the upper brainstem regions. The anterior cingulum associated with reactive postural control whereas the posterior cingulum correlated with anticipatory control. The spatial extent of associated cholinergic system changes were least for dynamic gait and sensory orientation functional domains compared to the anticipatory and reactive postural control functions. We conclude that specific aspects of dynamic balance and gait deficits in PD associate with overlapping but also distinct patterns of cerebral cholinergic system changes in numerous brain regions. Our study also presents novel evidence of cholinergic topography involved in dynamic balance and gait in PD that have not been typically associated with mobility disturbances, such as the right anterior temporal pole, right anterior part of the dorsomedial prefrontal cortex, gyrus rectus, fimbria, lingual gyrus, flocculus, nodulus, and right cerebellar hemisphere lobules VI and left crus I.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11382145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303381","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}
Brain communicationsPub Date : 2024-08-26eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae285
Crista A Minderhoud, Amber Postma, Floor E Jansen, Janneke R Zinkstok, Judith S Verhoeven, Bianca Berghuis, Wim M Otte, Marian J Jongmans, Kees P J Braun, Eva H Brilstra
{"title":"Quality of life in <i>SCN1A</i>-related seizure disorders across the lifespan.","authors":"Crista A Minderhoud, Amber Postma, Floor E Jansen, Janneke R Zinkstok, Judith S Verhoeven, Bianca Berghuis, Wim M Otte, Marian J Jongmans, Kees P J Braun, Eva H Brilstra","doi":"10.1093/braincomms/fcae285","DOIUrl":"10.1093/braincomms/fcae285","url":null,"abstract":"<p><p>This cohort study aims to describe the evolution of disease features and health-related quality of life per life stage in Dravet syndrome and other <i>SCN1A</i>-related non-Dravet seizure disorders which will enable treating physicians to provide tailored care. Health-related quality of life and disease features were assessed cross-sectionally in participants with a <i>SCN1A-</i>related seizure disorder, categorized per age group for Dravet syndrome, and longitudinally over seven years follow-up (2015-2022). Data were collected from questionnaires, medical records, and semi-structured telephonic interviews. Health-related quality of life was measured with the Paediatric Quality of Life Inventory, proxy-reported for participants with Dravet syndrome and for participants with non-Dravet aged younger than 18 years old and self-reported for participants with non-Dravet over 18 years old. Associations between health-related quality of life and disease features were explored with multivariable regression analyses, cross-sectionally in a cohort of 115 patients with Dravet and 48 patients with generalized epilepsy with febrile seizures plus and febrile seizures (non-Dravet) and longitudinally in a cohort of 52 Dravet patients and 13 non-Dravet patients. In the cross-sectional assessment in 2022, health-related quality of life was significantly lower in Dravet syndrome, compared to non-Dravet and normative controls. Health-related quality of life in the School and Psychosocial domain was significantly higher in older Dravet age groups. A higher health-related quality of life was associated with fewer behavioural problems [<i>β</i> = -1.1; 95% confidence interval (CI), (-1.4 to -0.8)], independent walking (<i>β</i> = 8.5; 95%CI (4.2-12.8)), compared to the use of a wheelchair), and fewer symptoms of autonomic dysfunction (<i>β</i> = -2.1, 95%CI (-3.2 to -1.0)). Longitudinally, health-related quality of life was significantly higher seven years later in the course of disease in Dravet participants (Δ8.9 standard deviation (SD) 18.0, <i>P</i> < 0.05), mediated by a lower prevalence of behavioural problems (<i>β</i> = -1.2, 95%CI (-2.0 to -0.4)), lower seizure frequency (<i>β</i> = -0.1, 95%CI (-0.2 to -0.0)) and older age (<i>β</i> = 0.03, 95%CI (0.01-0.04)). In summary, health-related quality of life was significantly higher at older age in Dravet syndrome. This finding may reflect the benefits of an advanced care strategy in recent years and a ceiling of severity of disease symptoms, possibly resulting in an increased wellbeing of parents and patients. The strong association with behavioural problems reinforces the need to incorporate a multidisciplinary approach, tailored to the age-specific needs of this patient group, into standard care.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142054","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}
Brain communicationsPub Date : 2024-08-22eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae275
Yawen Xiang, Mark A Rodrigues, Christine Lerpiniere, Tom J Moullaali, James J M Loan, Tim Wilkinson, Catherine A Humphreys, Colin Smith, Rustam Al-Shahi Salman, Neshika Samarasekera
{"title":"Factors associated with cognitive impairment before intracerebral haemorrhage: community-based neuropathological study.","authors":"Yawen Xiang, Mark A Rodrigues, Christine Lerpiniere, Tom J Moullaali, James J M Loan, Tim Wilkinson, Catherine A Humphreys, Colin Smith, Rustam Al-Shahi Salman, Neshika Samarasekera","doi":"10.1093/braincomms/fcae275","DOIUrl":"10.1093/braincomms/fcae275","url":null,"abstract":"<p><p>Little is known about whether clinical, radiological or neuropathological features are associated with cognitive impairment before intracerebral haemorrhage. We conducted a community-based cohort study of 125 adults with intracerebral haemorrhage (lobar <i>n</i> = 71, non-lobar <i>n</i> = 54) with consent to brain autopsy. We compared small vessel disease biomarkers on diagnostic CT head and neuropathological findings including neurofibrillary tangles and amyloid plaques in adults without cognitive impairment versus cognitive impairment without dementia versus dementia before intracerebral haemorrhage, stratified by lobar and non-lobar intracerebral haemorrhage. In non-lobar intracerebral haemorrhage, severe cortical atrophy was less common in those without cognitive impairment (8/36, 22%) and cognitive impairment without dementia (0/9, 0%) versus dementia (5/9, 56%); <i>P</i> = 0.008. Irrespective of intracerebral haemorrhage location, adults without cognitive impairment had milder neurofibrillary tangle pathology measured by median Braak stage (lobar intracerebral haemorrhage: no cognitive impairment 2 [interquartile range, 2-3] versus cognitive impairment without dementia 4 [2-6] versus dementia 5.5 [4-6]; <i>P</i> = 0.004; non-lobar intracerebral haemorrhage: no cognitive impairment 2 [1-2] versus cognitive impairment without dementia 2 [1-2] versus dementia 5 [3-6]; <i>P</i> < 0.001). Irrespective of intracerebral haemorrhage location, adults without cognitive impairment had milder amyloid plaque pathology measured by median Thal stage (lobar intracerebral haemorrhage: no cognitive impairment 2 [1-2] versus cognitive impairment without dementia 2 [2-3] versus dementia 2.5 [2-3.5]; <i>P</i> = 0.033; non-lobar intracerebral haemorrhage: no cognitive impairment 1 [0-1] versus cognitive impairment without dementia 0 [0-2] versus dementia 3 [2-3]; <i>P</i> = 0.002). Our findings suggest that irrespective of intracerebral haemorrhage location, adults with cognitive impairment before an intracerebral haemorrhage have more Alzheimer's disease neuropathologic change.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127645","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}
Brain communicationsPub Date : 2024-08-22eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae284
Erin C Conrad, Alfredo Lucas, William K S Ojemann, Carlos A Aguila, Marissa Mojena, Joshua J LaRocque, Akash R Pattnaik, Ryan Gallagher, Adam Greenblatt, Ashley Tranquille, Alexandra Parashos, Ezequiel Gleichgerrcht, Leonardo Bonilha, Brian Litt, Saurabh R Sinha, Lyle Ungar, Kathryn A Davis
{"title":"Interictal intracranial EEG asymmetry lateralizes temporal lobe epilepsy.","authors":"Erin C Conrad, Alfredo Lucas, William K S Ojemann, Carlos A Aguila, Marissa Mojena, Joshua J LaRocque, Akash R Pattnaik, Ryan Gallagher, Adam Greenblatt, Ashley Tranquille, Alexandra Parashos, Ezequiel Gleichgerrcht, Leonardo Bonilha, Brian Litt, Saurabh R Sinha, Lyle Ungar, Kathryn A Davis","doi":"10.1093/braincomms/fcae284","DOIUrl":"10.1093/braincomms/fcae284","url":null,"abstract":"<p><p>Patients with drug-resistant temporal lobe epilepsy often undergo intracranial EEG recording to capture multiple seizures in order to lateralize the seizure onset zone. This process is associated with morbidity and often ends in postoperative seizure recurrence. Abundant interictal (between-seizure) data are captured during this process, but these data currently play a small role in surgical planning. Our objective was to predict the laterality of the seizure onset zone using interictal intracranial EEG data in patients with temporal lobe epilepsy. We performed a retrospective cohort study (single-centre study for model development; two-centre study for model validation). We studied patients with temporal lobe epilepsy undergoing intracranial EEG at the University of Pennsylvania (internal cohort) and the Medical University of South Carolina (external cohort) between 2015 and 2022. We developed a logistic regression model to predict seizure onset zone laterality using several interictal EEG features derived from recent publications. We compared the concordance between the model-predicted seizure onset zone laterality and the side of surgery between patients with good and poor surgical outcomes. Forty-seven patients (30 female; ages 20-69; 20 left-sided, 10 right-sided and 17 bilateral seizure onsets) were analysed for model development and internal validation. Nineteen patients (10 female; ages 23-73; 5 left-sided, 10 right-sided, 4 bilateral) were analysed for external validation. The internal cohort cross-validated area under the curve for a model trained using spike rates was 0.83 for a model predicting left-sided seizure onset and 0.68 for a model predicting right-sided seizure onset. Balanced accuracies in the external cohort were 79.3% and 78.9% for the left- and right-sided predictions, respectively. The predicted concordance between the laterality of the seizure onset zone and the side of surgery was higher in patients with good surgical outcome. We replicated the finding that right temporal lobe epilepsy was harder to distinguish in a separate modality of resting-state functional MRI. In conclusion, interictal EEG signatures are distinct across seizure onset zone lateralities. Left-sided seizure onsets are easier to distinguish than right-sided onsets. A model trained on spike rates accurately identifies patients with left-sided seizure onset zones and predicts surgical outcome. A potential clinical application of these findings could be to either support or oppose a hypothesis of unilateral temporal lobe epilepsy when deciding to pursue surgical resection or ablation as opposed to device implantation.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11372416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134768","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}